The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS) (VALOR (Part C))

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02623699
Recruitment Status : Completed
First Posted : December 8, 2015
Results First Posted : July 28, 2023
Last Update Posted : July 28, 2023
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Amyotrophic Lateral Sclerosis
Interventions Drug: Tofersen
Drug: Placebo
Enrollment 176
Recruitment Details Participants were enrolled at the investigative sites in the Belgium, Canada, Denmark, France, Germany, Italy, Japan, United Kingdom, and the United States from 20 January 2016 to 16 July 2021.
Pre-assignment Details Study included SAD (Part A), MAD (Part B) and pivotal portions (Part C). Total 176 participants were randomized: 20 into Part A, 50 into Part B including 2 participants who completed Part A, were randomized in Part B after 12-week washout period, hence 2 participants were analysed in both Parts A, B (for total of 68 in Parts A, B), Part C randomized 108 participants.
Arm/Group Title Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively. Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1. Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1. Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2. Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3. Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection. Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection. Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and pharmacokinetic (PK) review of Cohort 5. Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and superoxide dismutase 1 (SOD1) pharmacodynamic (PD) review of Cohort 6. Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7. Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection. Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Period Title: Part A (Up to 63 Days)
Started 5 3 3 3 6 0 0 0 0 0 0 0
Completed 5 2 3 3 6 0 0 0 0 0 0 0
Not Completed 0 1 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Consent Withdrawn             0             1             0             0             0             0             0             0             0             0             0             0
Period Title: Part B (Up to 289 Days)
Started 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 12 [2] 10 [2] 9 [2] 9 [2] 10 [2] 0 0
Completed 0 0 0 0 0 10 8 9 8 10 0 0
Not Completed 0 0 0 0 0 2 2 0 1 0 0 0
Reason Not Completed
Lost to Follow-up             0             0             0             0             0             0             1             0             0             0             0             0
Consent Withdrawn             0             0             0             0             0             1             0             0             0             0             0             0
Death             0             0             0             0             0             1             1             0             1             0             0             0
[1]
Participants who completed Part A did not enter Part B of the study.
[2]
Started indicates the number of participants who were enrolled into Part B of the study.
Period Title: Part C (Up to 236 Days)
Started 0 0 0 0 0 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 36 [2] 72 [2]
Completed 0 0 0 0 0 0 0 0 0 0 33 64
Not Completed 0 0 0 0 0 0 0 0 0 0 3 8
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             0             0             0             0             2
Consent Withdrawn             0             0             0             0             0             0             0             0             0             0             1             2
Death             0             0             0             0             0             0             0             0             0             0             0             1
Disease Progression             0             0             0             0             0             0             0             0             0             0             2             3
[1]
Participants who completed Part B did not enter Part C of the study.
[2]
Started indicates the number of participants who were enrolled into Part C of the study.
Arm/Group Title Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg Total
Hide Arm/Group Description Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively. Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1. Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1. Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2. Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3. Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection. Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection. Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5. Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6. Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7. Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection. Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection. Total of all reporting groups
Overall Number of Baseline Participants 5 3 3 3 6 12 9 8 9 10 36 72 176
Hide Baseline Analysis Population Description
Intention-to-Treat (ITT) populations for parts A, B, and C included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Parts A, B, and C respectively. The demographics data reported for Part B arm groups included only the unique participants who were enrolled directly into Part B of the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 3 participants 3 participants 3 participants 6 participants 12 participants 9 participants 8 participants 9 participants 10 participants 36 participants 72 participants 176 participants
58.4  (9.29) 50.3  (7.64) 55.3  (17.62) 49.0  (3.61) 45.0  (12.82) 49.2  (11.04) 42.1  (11.19) 57.5  (11.75) 45.6  (10.71) 48.9  (10.80) 51.2  (11.57) 48.1  (12.64) 49.2  (12.02)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 3 participants 3 participants 3 participants 6 participants 12 participants 9 participants 8 participants 9 participants 10 participants 36 participants 72 participants 176 participants
Female
2
  40.0%
3
 100.0%
0
   0.0%
1
  33.3%
4
  66.7%
5
  41.7%
3
  33.3%
5
  62.5%
3
  33.3%
6
  60.0%
17
  47.2%
29
  40.3%
78
  44.3%
Male
3
  60.0%
0
   0.0%
3
 100.0%
2
  66.7%
2
  33.3%
7
  58.3%
6
  66.7%
3
  37.5%
6
  66.7%
4
  40.0%
19
  52.8%
43
  59.7%
98
  55.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 3 participants 3 participants 3 participants 6 participants 12 participants 9 participants 8 participants 9 participants 10 participants 36 participants 72 participants 176 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.8%
4
   5.6%
5
   2.8%
Not Hispanic or Latino
4
  80.0%
3
 100.0%
3
 100.0%
1
  33.3%
5
  83.3%
9
  75.0%
4
  44.4%
5
  62.5%
4
  44.4%
7
  70.0%
28
  77.8%
47
  65.3%
120
  68.2%
Unknown or Not Reported
1
  20.0%
0
   0.0%
0
   0.0%
2
  66.7%
1
  16.7%
3
  25.0%
5
  55.6%
3
  37.5%
5
  55.6%
3
  30.0%
7
  19.4%
21
  29.2%
51
  29.0%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 5 participants 3 participants 3 participants 3 participants 6 participants 12 participants 9 participants 8 participants 9 participants 10 participants 36 participants 72 participants 176 participants
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  12.5%
0
   0.0%
0
   0.0%
4
  11.1%
5
   6.9%
10
   5.7%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
1
   0.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.6%
White
4
  80.0%
3
 100.0%
3
 100.0%
1
  33.3%
5
  83.3%
7
  58.3%
4
  44.4%
4
  50.0%
4
  44.4%
7
  70.0%
25
  69.4%
44
  61.1%
111
  63.1%
Not Reported
1
  20.0%
0
   0.0%
0
   0.0%
2
  66.7%
1
  16.7%
3
  25.0%
5
  55.6%
3
  37.5%
5
  55.6%
3
  30.0%
7
  19.4%
21
  29.2%
51
  29.0%
Other
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
2
   1.1%
[1]
Measure Description: Not reported indicates that race data was not reported due to confidentiality regulations.
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 21 participants 39 participants 60 participants
35.4  (5.66) 36.0  (6.40) 35.78  (6.109)
[1]
Measure Description: ALSFRS-R measures respiratory, bulbar function, gross, and fine motor skills. 12 questions, each scored from 0-4 (no-full function), for a total score of 48. Scores decline with disease progression. Higher scores represent better function.
[2]
Measure Analysis Population Description: Modified ITT (mITT) population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part C arms groups.
Cerebrospinal Fluid (CSF) Levels of Total SOD1 Protein Concentration   [1] 
Geometric Mean (Full Range)
Unit of measure:  Nanograms per milliliter (ng/mL)
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 4 participants 9 participants 1 participants 1 participants 4 participants 21 participants 39 participants 79 participants
70.40
(57.2 to 87.9)
102.00
(102.00 to 102.00)
125.00
(125.00 to 125.00)
82.80
(82.8 to 82.8)
135.86
(92.5 to 199.0)
107.07
(60.0 to 322.0)
103.32
(38.8 to 282.0)
104.64
(38.8 to 322.0)
[1]
Measure Analysis Population Description: Pharmacodynamic (PD) population is subset of ITT population with at least 1 post-dose PD measurement in Part B. mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part B and C arms groups.
Percentage Predicted Slow Vital Capacity (SVC)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent predicted
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 21 participants 39 participants 60 participants
83.7  (17.87) 80.3  (14.22) 81.50  (15.533)
[1]
Measure Analysis Population Description: mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part C arms groups.
Handheld Dynamometry (HHD) Megascore as Measured by the HHD Device   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 21 participants 39 participants 60 participants
0.0  (0.60) 0.0  (0.67) -0.007  (0.6396)
[1]
Measure Description: 16 muscle groups were evaluated in upper, lower extremities. Muscle strength values were normalized to Z scores as (post-baseline measurements - mean)/standard deviation (SD), averaged to provide HHD overall megascore.
[2]
Measure Analysis Population Description: mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part C arms groups.
Neurofilament Light Chain (NfL) Concentration in Plasma   [1] 
Geometric Mean (Full Range)
Unit of measure:  Picograms per mL (pg/mL)
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 21 participants 39 participants 60 participants
92.7
(9 to 370)
121.8
(12 to 329)
110.49
(8.8 to 370.4)
[1]
Measure Analysis Population Description: mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part C arms groups.
1.Primary Outcome
Title Parts A and B: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.
Time Frame Part A: First dose up to Day 63; Part B: First dose up to Day 289
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Arm/Group Title Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 5 3 3 3 6 12 10 9 9 10
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
2
  40.0%
2
  66.7%
3
 100.0%
3
 100.0%
6
 100.0%
12
 100.0%
10
 100.0%
9
 100.0%
9
 100.0%
10
 100.0%
SAEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  16.7%
2
  20.0%
1
  11.1%
2
  22.2%
0
   0.0%
2.Primary Outcome
Title Parts A and B: Number of Participants With Clinically Significant Laboratory Abnormalities
Hide Description Clinical laboratory assessments included hematology, chemistry, and urinalysis.
Time Frame Part A: Up to Day 57; Part B: Up to Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Arm/Group Title Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 5 3 3 3 6 12 10 9 9 10
Measure Type: Count of Participants
Unit of Measure: Participants
Pleocytosis
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  20.0%
1
  11.1%
0
   0.0%
0
   0.0%
Eosinophilia
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
Blood Phosphorus Decreased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
CSF Protein Increased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
4
  44.4%
1
  10.0%
CSF White Blood Cell Count Increased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
3
  33.3%
0
   0.0%
CSF White Blood Cell Count Positive
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
Gamma-Glutamyltransferase Increased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Output Decreased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Parts A and B: Number of Participants With Clinically Significant Vital Sign Abnormalities
Hide Description The criteria for clinically significant vital sign abnormalities include: Temperature: >38 degree Celsius (°C) or an increase from baseline of ≥1°C; Pulse: >120 beats per minute (bpm) or an increase from baseline of >20 bpm, <50 bpm or a decrease from baseline of >20 bpm; Systolic blood pressure (BP): >180 mmHg or an increase from baseline of >40 mmHg, <90 mmHg or a decrease from baseline of >30 mmHg; Diastolic BP: >105 mmHg or an increase from baseline of >30 mmHg, <50 mmHg or a decrease from baseline of >20 mmHg.
Time Frame Part A: Up to Day 57; Part B: Up to Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Arm/Group Title Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 5 3 3 3 6 12 10 9 9 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Parts A and B: Number of Participants With Clinically Significant Physical Examination Abnormalities
Hide Description Clinically significant physical examination abnormalities included weight decreased.
Time Frame Part A: Up to Day 57; Part B: Up to Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Arm/Group Title Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 5 3 3 3 6 12 10 9 9 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
5.Primary Outcome
Title Parts A and B: Number of Participants With Clinically Significant Neurological Examination Abnormalities
Hide Description Clinically significant neurological examination abnormalities included hyporeflexia.
Time Frame Part A: Up to Day 57; Part B: Up to Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Arm/Group Title Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 5 3 3 3 6 12 10 9 9 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6.Primary Outcome
Title Parts A and B: Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Abnormalities
Hide Description [Not Specified]
Time Frame Part A: Up to Day 57; Part B: Up to Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Arm/Group Title Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 5 3 3 3 6 12 10 9 9 10
Measure Type: Count of Participants
Unit of Measure: Participants
Maximum Increase From Baseline QTcF > 30 to 60 ms
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
  25.0%
1
  10.0%
2
  22.2%
2
  22.2%
3
  30.0%
Maximum Post-baseline QTcF > 480 to 500 ms
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7.Primary Outcome
Title Parts A and B: PK Parameter of BIIB067 in Plasma: Maximum Observed Concentration (Cmax)
Hide Description [Not Specified]
Time Frame Part A: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1; Part B: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1 and 1, 2, 4, 6 hrs post-dose on Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
PK population is the subset of the ITT population (all randomized participants who received at least 1 dose or a part of 1 dose of study treatment) of participants with at least 1 post-dose PK measurement in Part A or B. Data was not collected for participants on Day 85 for Part A of the study.
Arm/Group Title Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 3 3 3 6 10 9 9 10
Geometric Mean (Full Range)
Unit of Measure: ng/mL
Day 1 Number Analyzed 3 participants 3 participants 3 participants 6 participants 10 participants 9 participants 9 participants 10 participants
64.94
(38.8 to 159.0)
75.06
(43.0 to 144.0)
202.09
(174.0 to 236.0)
529.63
(148.0 to 1450.0)
80.75
(20.1 to 393.0)
229.41
(26.3 to 948.0)
437.28
(128.0 to 1930.0)
1031.74
(285.0 to 3530.0)
Day 85 Number Analyzed 0 participants 0 participants 0 participants 0 participants 10 participants 9 participants 9 participants 10 participants
112.74
(29.7 to 203.0)
199.69
(93.6 to 537.0)
411.00
(74.1 to 1450.0)
1181.83
(170.0 to 3990.0)
8.Primary Outcome
Title Parts A and B: PK Parameter of BIIB067 in Plasma: Time to Reach Maximum Observed Concentration (Tmax)
Hide Description [Not Specified]
Time Frame Part A: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1; Part B: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1 and 1, 2, 4, 6 hrs post-dose on Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B. Data was not collected for participants on Day 85 for Part A of the study.
Arm/Group Title Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 3 3 3 6 10 9 9 10
Geometric Mean (Full Range)
Unit of Measure: hours
Day 1 Number Analyzed 3 participants 3 participants 3 participants 6 participants 10 participants 9 participants 9 participants 10 participants
4.58
(4.0 to 6.0)
4.16
(2.0 to 6.0)
6.00
(6.0 to 6.0)
2.70
(2.0 to 6.0)
7.01
(2.0 to 24.0)
3.68
(1.0 to 6.0)
2.44
(1.0 to 6.0)
3.67
(1.0 to 24.0)
Day 85 Number Analyzed 0 participants 0 participants 0 participants 0 participants 10 participants 9 participants 9 participants 10 participants
3.93
(2.0 to 6.0)
3.97
(1.0 to 6.0)
3.12
(1.0 to 6.0)
3.82
(1.0 to 6.0)
9.Primary Outcome
Title Parts A and B: PK Parameter of BIIB067 in Plasma: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)
Hide Description [Not Specified]
Time Frame Parts A and B: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Arm/Group Title Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 3 3 3 6 10 9 9 10
Geometric Mean (Full Range)
Unit of Measure: hour*ng/mL
879.86
(550.8 to 1989.5)
1027.18
(879.2 to 1263.2)
2873.77
(2347.2 to 3543.4)
5196.11
(2410.2 to 10977.3)
1009.85
(372.8 to 2192.3)
2875.13
(541.1 to 6984.8)
4289.16
(1347.6 to 10637.1)
11344.47
(4025.5 to 26143.0)
10.Primary Outcome
Title Parts A and B: PK Parameter of BIIB067 in Plasma: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
Hide Description [Not Specified]
Time Frame Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
Hide Outcome Measure Data
Hide Analysis Population Description
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Arm/Group Title Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 3 3 3 6 10 9 9 10
Mean (Standard Deviation)
Unit of Measure: hour*ng/mL
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the AUC0-infinity values.
11.Primary Outcome
Title Parts A and B: PK Parameter of BIIB067 in Plasma: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast)
Hide Description [Not Specified]
Time Frame Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
Hide Outcome Measure Data
Hide Analysis Population Description
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Arm/Group Title Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 3 3 3 6 10 9 9 10
Mean (Standard Deviation)
Unit of Measure: hour*ng/mL
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
Due to the large number of values below the level of quantification at various times, the last measurable concentration would have varied across individuals which makes this parameter not useful.
12.Primary Outcome
Title Parts A and B: PK Parameter of BIIB067 in Plasma: Apparent Terminal Elimination Half-life (t1/2)
Hide Description [Not Specified]
Time Frame Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
Hide Outcome Measure Data
Hide Analysis Population Description
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Arm/Group Title Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 3 3 3 6 10 9 9 10
Median (Inter-Quartile Range)
Unit of Measure: hours
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the apparent terminal t1/2 values.
13.Primary Outcome
Title Parts A and B: PK Parameters of BIIB067 in CSF Levels: Terminal Elimination Half-life (t1/2)
Hide Description [Not Specified]
Time Frame Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
Hide Outcome Measure Data
Hide Analysis Population Description
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Arm/Group Title Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 3 3 3 6 10 9 9 10
Median (Inter-Quartile Range)
Unit of Measure: hours
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the terminal t1/2 values.
14.Primary Outcome
Title Part C: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score at Week 28
Hide Description The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 (no function) to 4 (full function), for a total possible score of 48. Scores decline with disease progression. ALSFRS-R scores calculated at diagnosis can be compared to scores throughout time to determine the speed of progression. Higher scores represent better function, negative change from baseline indicates disease progression.
Time Frame Baseline, Week 28 (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Arm/Group Title Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Overall Number of Participants Analyzed 21 39
Least Squares Mean (Standard Error)
Unit of Measure: score on scale
-8.1  (1.79) -7.0  (1.42)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part C-Pivotal: Placebo, Part C-Pivotal: BIIB067 100 mg
Comments Joint rank test combining function and mortality were used for statistical inference and the estimates were from the Analysis of covariance (ANCOVA) for change from baseline. Multiple imputation was used to handle missing data for withdrawals other than death in the joint rank analysis. Multiple imputation was used to handle all missing data in the ANCOVA for change from baseline.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.9689
Comments Joint rank p-value was calculated from ANCOVA model which included treatment as fixed effect, adjusts for covariates: Baseline disease duration since symptom onset, baseline ALSFRS-R total score, and use of riluzole or edaravone.
Method Joint rank
Comments [Not Specified]
Method of Estimation Estimation Parameter least square (LS) mean difference
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-3.19 to 5.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.22
Estimation Comments ANCOVA model included treatment as a fixed effect, adjusts for the covariates: Baseline disease duration since symptom onset, baseline ALSFRS-R total score, and use of riluzole or edaravone.
15.Secondary Outcome
Title Part B: CSF Levels of Total SOD1 Protein Concentration Ratio to Baseline
Hide Description Total CSF SOD1 protein ratio to baseline was calculated.
Time Frame Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
PD population is the subset of the ITT population with at least 1 post-dose PD measurement in Part B.
Arm/Group Title Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Overall Number of Participants Analyzed 12 10 9 8 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
0.97
(0.83 to 1.13)
0.99
(0.83 to 1.18)
0.73
(0.61 to 0.87)
0.79
(0.66 to 0.94)
0.64
(0.55 to 0.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B-MAD: Combined Placebo, Part B-MAD: Cohort 5: BIIB067 20 mg
Comments Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS geometric mean ratio
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.53 to 0.84
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B-MAD: Combined Placebo, Part B-MAD: Cohort 6: BIIB067 40 mg
Comments Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0002
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS geometric mean ratio
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.60 to 0.95
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B-MAD: Combined Placebo, Part B-MAD: Cohort 7: BIIB067 60 mg
Comments Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0641
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS geometric mean ratio
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.65 to 1.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B-MAD: Combined Placebo, Part B-MAD: Cohort 8: BIIB067 100 mg
Comments Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS geometric mean ratio
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.53 to 0.84
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Part C: CSF Levels of Total SOD1 Protein Concentration Ratio to Baseline
Hide Description Total CSF SOD1 protein ratio to baseline was calculated and LS Geometric Mean ratio to baseline was reported.
Time Frame Week 28 (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Arm/Group Title Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Overall Number of Participants Analyzed 21 39
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: ratio
1.16
(0.96 to 1.40)
0.71
(0.62 to 0.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part C-Pivotal: Placebo, Part C-Pivotal: BIIB067 100 mg
Comments The ANCOVA model included covariates for the corresponding baseline value i.e. log value, baseline disease duration since symptom onset, and use of riluzole or edaravone. Multiple imputation was used to handle missing data for withdrawals. Difference in LS geometric mean ratio to baseline (BIIB067:Placebo) was calculated.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The analysis was based on ANCOVA model with natural log transformed data. P-value for this secondary outcome measure (OM) is nominal as statistical significance was not met on the primary OM.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS geometric mean ratio
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.49 to 0.78
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Part C: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline
Hide Description NfL is a biomarker whose concentration was assessed in plasma. Plasma NfL ratio to baseline was calculated.
Time Frame Baseline, Day 197 (Week 28)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Arm/Group Title Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Overall Number of Participants Analyzed 21 39
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: ratio
1.20
(0.94 to 1.52)
0.40
(0.33 to 0.48)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part C-Pivotal: Placebo, Part C-Pivotal: BIIB067 100 mg
Comments Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The analysis was based on ANCOVA model with natural log transformed data. The model included covariates for the corresponding baseline value i.e. log value, baseline disease duration since symptom onset, and use of riluzole or edaravone.
Method ANCOVA
Comments P-value for this secondary OM is nominal as statistical significance was not met on the primary OM.
Method of Estimation Estimation Parameter Difference in LS geometric mean ratio
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.25 to 0.45
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Part C: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC) at Week 28
Hide Description Vital capacity was measured by means of an SVC test, administered in the upright position.
Time Frame Baseline, Week 28 (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Arm/Group Title Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Overall Number of Participants Analyzed 21 39
Least Squares Mean (Standard Error)
Unit of Measure: percent predicted
-22.20  (4.771) -14.31  (3.557)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part C-Pivotal: Placebo, Part C-Pivotal: BIIB067 100 mg
Comments Joint rank test combining function and mortality were used for statistical inference and the estimates were from the ANCOVA for change from baseline. Multiple imputation was used to handle missing data for withdrawals other than death in the joint rank analysis. Multiple imputation was used to handle all missing data in the ANCOVA for change from baseline.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.3233
Comments Joint rank p-value was calculated from ANCOVA model which included treatment as fixed effect, adjusts for covariates: Baseline disease duration since symptom onset, baseline ALSFRS-R total score, baseline SVC, and use of riluzole or edaravone.
Method Joint rank
Comments P-value for this secondary OM is nominal as statistical significance was not met on the primary OM.
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 7.90
Confidence Interval (2-Sided) 95%
-3.528 to 19.322
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.829
Estimation Comments ANCOVA model included treatment as a fixed effect, adjusts for the covariates: Baseline disease duration since symptom onset, baseline ALSFRS-R total score, baseline SVC, and use of riluzole or edaravone.
19.Secondary Outcome
Title Part C: Change From Baseline in Handheld Dynamometry (HHD) Megascore as Measured by the HHD Device at Week 28
Hide Description Quantitative muscle strength was evaluated using HHD, which tests isometric strength of multiple muscles using standard participant positioning. Sixteen muscle groups were evaluated in both upper and lower extremities. The muscle strength values were normalized to Z scores as (post-baseline measurements - mean)/SD and averaged to provide HHD overall megascore. The overall megascore was created by averaging all eight bilateral measurement Z scores, if no more than 10 (≤ 10) measures are missing. A negative change from baseline indicated decreased muscle strength.
Time Frame Baseline, Week 28 (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Arm/Group Title Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Overall Number of Participants Analyzed 21 39
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.37  (0.096) -0.34  (0.073)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part C-Pivotal: Placebo, Part C-Pivotal: BIIB067 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.8390
Comments ANCOVA model included treatment as fixed effect and adjusts for following covariates: Baseline disease duration since symptom onset, baseline HHD overall megascore, and use of riluzole/edaravone. Missing data were handled using multiple imputation.
Method ANCOVA
Comments P-value for this secondary OM is nominal as statistical significance was not met on the primary OM.
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.207 to 0.255
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.118
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Part C: Time to Death or Permanent Ventilation
Hide Description Time to Death or Permanent Ventilation is defined as the time to the earliest occurrence of one of the following events that were adjudicated by an independent committee: Death; Permanent ventilation (≥22 hours of mechanical ventilation [invasive or noninvasive] per day for ≥21 consecutive days).
Time Frame Baseline up to Week 28 (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Arm/Group Title Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Overall Number of Participants Analyzed 21 39
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not estimated due to insufficient number of participants with events.
21.Secondary Outcome
Title Part C: Time to Death
Hide Description [Not Specified]
Time Frame Baseline up to Week 28 (Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Arm/Group Title Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Overall Number of Participants Analyzed 21 39
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not estimated due to insufficient number of participants with events.
22.Secondary Outcome
Title Part C: Number of Participants Experiencing AEs and SAEs
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.
Time Frame First dose up to Day 236
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants in Part C who were randomized and received at least one dose of study treatment.
Arm/Group Title Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description:
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Overall Number of Participants Analyzed 36 72
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
34
  94.4%
69
  95.8%
SAEs
5
  13.9%
13
  18.1%
Time Frame Part A: First dose up to Day 63; Part B: First dose up to Day 289; Part C: First dose up to Day 236
Adverse Event Reporting Description Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B. Safety population included all participants in Part C who were randomized and received at least one dose of study treatment. MedDRA version for Parts A and B: 22.0, Part C: 24.0
 
Arm/Group Title Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Hide Arm/Group Description Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively. Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1. Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1. Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2. Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3. Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection. Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection. Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5. Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6. Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7. Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection. Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
All-Cause Mortality
Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/5 (0.00%)   0/3 (0.00%)   0/3 (0.00%)   0/3 (0.00%)   0/6 (0.00%)   1/12 (8.33%)   1/10 (10.00%)   0/9 (0.00%)   1/9 (11.11%)   0/10 (0.00%)   0/36 (0.00%)   1/72 (1.39%) 
Hide Serious Adverse Events
Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/5 (0.00%)   0/3 (0.00%)   0/3 (0.00%)   0/3 (0.00%)   0/6 (0.00%)   2/12 (16.67%)   2/10 (20.00%)   1/9 (11.11%)   2/9 (22.22%)   0/10 (0.00%)   5/36 (13.89%)   13/72 (18.06%) 
Cardiac disorders                         
Cardiac failure congestive † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Gastrointestinal disorders                         
Faecaloma † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
General disorders                         
Hypothermia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Impaired self-care † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Respiratory complication associated with device † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Infections and infestations                         
Myelitis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Injury, poisoning and procedural complications                         
Fibula fracture † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Meningitis chemical † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Investigations                         
Csf protein increased † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Csf white blood cell count increased † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Metabolism and nutrition disorders                         
Dehydration † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  0/72 (0.00%) 
Nervous system disorders                         
Loss of consciousness † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Lumbar radiculopathy † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Myelitis transverse † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Respiratory, thoracic and mediastinal disorders                         
Acute respiratory failure † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Aspiration † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Atelectasis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  0/72 (0.00%) 
Dyspnoea † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  0/72 (0.00%) 
Pneumonia aspiration † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  2/72 (2.78%) 
Pulmonary embolism † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  3/72 (4.17%) 
Respiratory failure † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/9 (11.11%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Vascular disorders                         
Deep vein thrombosis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A-SAD: Combined Placebo Part A-SAD: Cohort 1: BIIB067 10 mg Part A-SAD: Cohort 2: BIIB067 20 mg Part A-SAD: Cohort 3: BIIB067 40 mg Part A-SAD: Cohort 4: BIIB067 60 mg Part B-MAD: Combined Placebo Part B-MAD: Cohort 5: BIIB067 20 mg Part B-MAD: Cohort 6: BIIB067 40 mg Part B-MAD: Cohort 7: BIIB067 60 mg Part B-MAD: Cohort 8: BIIB067 100 mg Part C-Pivotal: Placebo Part C-Pivotal: BIIB067 100 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/5 (40.00%)   2/3 (66.67%)   3/3 (100.00%)   3/3 (100.00%)   6/6 (100.00%)   11/12 (91.67%)   10/10 (100.00%)   9/9 (100.00%)   9/9 (100.00%)   10/10 (100.00%)   34/36 (94.44%)   68/72 (94.44%) 
Blood and lymphatic system disorders                         
Eosinophilia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Cardiac disorders                         
Atrial fibrillation † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Tachycardia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Ear and labyrinth disorders                         
Ear pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Gastrointestinal disorders                         
Abdominal distension † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  2/72 (2.78%) 
Abdominal pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  2/72 (2.78%) 
Abdominal pain lower † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Constipation † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  4/36 (11.11%)  6/72 (8.33%) 
Diarrhoea † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  5/36 (13.89%)  1/72 (1.39%) 
Dyspepsia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Dysphagia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  1/72 (1.39%) 
Faeces discoloured † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Gastritis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  0/72 (0.00%) 
Gastrointestinal disorder † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Gingival pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Lip swelling † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Nausea † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  2/9 (22.22%)  1/9 (11.11%)  2/10 (20.00%)  6/36 (16.67%)  9/72 (12.50%) 
Salivary hypersecretion † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  1/9 (11.11%)  1/10 (10.00%)  1/36 (2.78%)  4/72 (5.56%) 
Toothache † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  2/9 (22.22%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
General disorders                         
Asthenia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  0/72 (0.00%) 
Chest pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Fatigue † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  2/12 (16.67%)  1/10 (10.00%)  1/9 (11.11%)  2/9 (22.22%)  2/10 (20.00%)  2/36 (5.56%)  12/72 (16.67%) 
Feeling abnormal † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Feeling hot † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Influenza like illness † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  1/72 (1.39%) 
Infusion site bruising † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Infusion site swelling † 1  0/5 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Oedema peripheral † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  2/72 (2.78%) 
Pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  7/72 (9.72%) 
Peripheral swelling † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  1/36 (2.78%)  1/72 (1.39%) 
Pyrexia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  1/10 (10.00%)  1/36 (2.78%)  3/72 (4.17%) 
Immune system disorders                         
Dust allergy † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Infections and infestations                         
Bronchitis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  0/72 (0.00%) 
Ear infection † 1  0/5 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Fungal skin infection † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  2/9 (22.22%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  0/72 (0.00%) 
Gastric infection † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Gastroenteritis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  0/72 (0.00%) 
Hordeolum † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Influenza † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  1/36 (2.78%)  1/72 (1.39%) 
Labyrinthitis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Lower respiratory tract infection † 1  0/5 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Nasopharyngitis † 1  0/5 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  2/10 (20.00%)  1/9 (11.11%)  3/9 (33.33%)  1/10 (10.00%)  7/36 (19.44%)  2/72 (2.78%) 
Oral herpes † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Pharyngitis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Pneumonia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Respiratory tract infection † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Sinusitis † 1  0/5 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  1/72 (1.39%) 
Systemic viral infection † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Tooth abscess † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Upper respiratory tract infection † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  4/10 (40.00%)  0/9 (0.00%)  2/9 (22.22%)  0/10 (0.00%)  2/36 (5.56%)  5/72 (6.94%) 
Urinary tract infection † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  2/10 (20.00%)  2/36 (5.56%)  2/72 (2.78%) 
Viral upper respiratory tract infection † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Injury, poisoning and procedural complications                         
Accident † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Arthropod bite † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  1/9 (11.11%)  1/9 (11.11%)  0/10 (0.00%)  1/36 (2.78%)  0/72 (0.00%) 
Contusion † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  2/10 (20.00%)  1/9 (11.11%)  0/9 (0.00%)  2/10 (20.00%)  1/36 (2.78%)  3/72 (4.17%) 
Fall † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  3/12 (25.00%)  3/10 (30.00%)  3/9 (33.33%)  2/9 (22.22%)  5/10 (50.00%)  15/36 (41.67%)  17/72 (23.61%) 
Foot fracture † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Head injury † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  1/36 (2.78%)  0/72 (0.00%) 
Joint injury † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Ligament sprain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  2/9 (22.22%)  0/10 (0.00%)  2/36 (5.56%)  4/72 (5.56%) 
Muscle strain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  1/36 (2.78%)  1/72 (1.39%) 
Musculoskeletal procedural complication † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  3/36 (8.33%)  3/72 (4.17%) 
Nasal injury † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Post lumbar puncture syndrome † 1  1/5 (20.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  3/12 (25.00%)  4/10 (40.00%)  3/9 (33.33%)  3/9 (33.33%)  3/10 (30.00%)  11/36 (30.56%)  13/72 (18.06%) 
Post procedural complication † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  4/36 (11.11%)  3/72 (4.17%) 
Post procedural contusion † 1  0/5 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  2/10 (20.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Post procedural discomfort † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  0/72 (0.00%) 
Post-traumatic pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Procedural anxiety † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Procedural complication † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  1/36 (2.78%)  2/72 (2.78%) 
Procedural dizziness † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Procedural headache † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Procedural nausea † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  2/72 (2.78%) 
Procedural pain † 1  1/5 (20.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  3/6 (50.00%)  5/12 (41.67%)  4/10 (40.00%)  1/9 (11.11%)  4/9 (44.44%)  7/10 (70.00%)  21/36 (58.33%)  41/72 (56.94%) 
Skin abrasion † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  3/36 (8.33%)  3/72 (4.17%) 
Skin laceration † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  3/36 (8.33%)  0/72 (0.00%) 
Subcutaneous haematoma † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Sunburn † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Tibia fracture † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  1/72 (1.39%) 
Vaccination complication † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  1/72 (1.39%) 
Investigations                         
Blood phosphorus decreased † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Csf protein increased † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  3/9 (33.33%)  1/10 (10.00%)  1/36 (2.78%)  6/72 (8.33%) 
Csf white blood cell count increased † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  2/9 (22.22%)  0/10 (0.00%)  0/36 (0.00%)  7/72 (9.72%) 
Csf white blood cell count positive † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Gamma-glutamyltransferase increased † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Urine output decreased † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Weight decreased † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  2/36 (5.56%)  0/72 (0.00%) 
Metabolism and nutrition disorders                         
Decreased appetite † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  1/36 (2.78%)  3/72 (4.17%) 
Diabetes mellitus inadequate control † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Type 2 diabetes mellitus † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  0/72 (0.00%) 
Musculoskeletal and connective tissue disorders                         
Arthralgia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  1/9 (11.11%)  1/9 (11.11%)  2/10 (20.00%)  2/36 (5.56%)  10/72 (13.89%) 
Back pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  0/12 (0.00%)  1/10 (10.00%)  1/9 (11.11%)  1/9 (11.11%)  5/10 (50.00%)  2/36 (5.56%)  15/72 (20.83%) 
Bursitis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Flank pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  2/72 (2.78%) 
Joint swelling † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  2/36 (5.56%)  1/72 (1.39%) 
Muscle spasms † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  5/72 (6.94%) 
Muscle tightness † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Muscular weakness † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  1/10 (10.00%)  4/36 (11.11%)  4/72 (5.56%) 
Musculoskeletal pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  4/72 (5.56%) 
Musculoskeletal stiffness † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  4/72 (5.56%) 
Myalgia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  2/9 (22.22%)  0/10 (0.00%)  2/36 (5.56%)  10/72 (13.89%) 
Neck pain † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  3/12 (25.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  4/36 (11.11%)  4/72 (5.56%) 
Pain in extremity † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/6 (16.67%)  2/12 (16.67%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  3/10 (30.00%)  6/36 (16.67%)  19/72 (26.39%) 
Nervous system disorders                         
Balance disorder † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Dizziness † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  3/10 (30.00%)  3/36 (8.33%)  4/72 (5.56%) 
Dysaesthesia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  1/72 (1.39%) 
Headache † 1  0/5 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  1/3 (33.33%)  1/6 (16.67%)  7/12 (58.33%)  4/10 (40.00%)  2/9 (22.22%)  4/9 (44.44%)  6/10 (60.00%)  16/36 (44.44%)  33/72 (45.83%) 
Hypoaesthesia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  3/72 (4.17%) 
Hyporeflexia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Migraine † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  1/36 (2.78%)  2/72 (2.78%) 
Muscle contractions involuntary † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  4/72 (5.56%) 
Muscle spasticity † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  1/72 (1.39%) 
Nerve compression † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  0/72 (0.00%) 
Neuralgia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  4/72 (5.56%) 
Paraesthesia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  6/36 (16.67%)  6/72 (8.33%) 
Peroneal nerve palsy † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Pleocytosis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  3/72 (4.17%) 
Sinus headache † 1  0/5 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  0/72 (0.00%) 
Psychiatric disorders                         
Anxiety † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  1/10 (10.00%)  3/36 (8.33%)  4/72 (5.56%) 
Depression † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  3/36 (8.33%)  1/72 (1.39%) 
Insomnia † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  3/36 (8.33%)  3/72 (4.17%) 
Renal and urinary disorders                         
Dysuria † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Urinary incontinence † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Urinary retention † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Respiratory, thoracic and mediastinal disorders                         
Choking † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  0/72 (0.00%) 
Cough † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  1/36 (2.78%)  5/72 (6.94%) 
Dyspnoea † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/9 (11.11%)  1/9 (11.11%)  0/10 (0.00%)  5/36 (13.89%)  4/72 (5.56%) 
Oropharyngeal pain † 1  0/5 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  2/36 (5.56%)  2/72 (2.78%) 
Respiratory symptom † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Rhinorrhoea † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Sleep apnoea syndrome † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Sputum discoloured † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Upper respiratory tract congestion † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Upper-airway cough syndrome † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Skin and subcutaneous tissue disorders                         
Cold sweat † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Decubitus ulcer † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Dermatitis allergic † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  1/72 (1.39%) 
Eczema † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Erythema † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  1/36 (2.78%)  0/72 (0.00%) 
Miliaria † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Night sweats † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  0/72 (0.00%) 
Pruritus † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  1/36 (2.78%)  3/72 (4.17%) 
Rash † 1  0/5 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/10 (10.00%)  0/36 (0.00%)  2/72 (2.78%) 
Rash pruritic † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Skin disorder † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Skin plaque † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Vascular disorders                         
Deep vein thrombosis † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  0/72 (0.00%) 
Flushing † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/10 (0.00%)  0/36 (0.00%)  0/72 (0.00%) 
Hypertension † 1  0/5 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/10 (0.00%)  2/36 (5.56%)  1/72 (1.39%) 
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: US Biogen Clinical Trial Center
Organization: Biogen
Phone: 866-633-4636
EMail: clinicaltrials@biogen.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02623699    
Other Study ID Numbers: 233AS101
2015-004098-33 ( EudraCT Number )
First Submitted: November 24, 2015
First Posted: December 8, 2015
Results First Submitted: May 17, 2023
Results First Posted: July 28, 2023
Last Update Posted: July 28, 2023