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Study of Nivolumab in Patients With Classical Hodgkin's Lymphoma (Registrational) (CheckMate 205)

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ClinicalTrials.gov Identifier: NCT02181738
Recruitment Status : Completed
First Posted : July 4, 2014
Results First Posted : December 11, 2018
Last Update Posted : November 28, 2023
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hodgkin Disease
Interventions Drug: Nivolumab
Drug: Doxorubicin
Drug: Vinblastine
Drug: Dacarbazine
Enrollment 294
Recruitment Details 243 participants were treated at 34 sites in 10 countries for cohorts A, B, and C. Cohort D enrolled separately. 51 participants were treated in cohort D for a total of 294 participants treated all together.
Pre-assignment Details  
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Period Title: Overall Study
Started 63 80 100 51
N-AVD Combination Therapy Phase [1] 0 0 0 49
N-AVD Combination Therapy Phase [2] 0 0 0 1
Completed [3] 0 0 13 45
Not Completed 63 80 87 6
Reason Not Completed
Participant Withdrew Consent             2             1             1             1
Lost to Follow-up             1             2             1             1
Participant no Longer Meets Study Criteria             0             0             0             1
Poor/Non-Compliance             1             0             2             1
Disease Progression             28             35             40             0
Participant Request to Discontinue Study Treatment             5             12             5             1
Study Drug Toxicity             6             11             8             1
Other Reasons             14             16             28             0
Maximum Clinical Benefit             3             0             1             0
Adverse Event Unrelated to Study Drug             3             3             1             0
[1]
Received N-AVD
[2]
Received only AVD
[3]
Completed = completed treatment as per protocol
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV) Total
Hide Arm/Group Description Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase). Total of all reporting groups
Overall Number of Baseline Participants 63 80 100 51 294
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 63 participants 80 participants 100 participants 51 participants 294 participants
36.3  (12.54) 38.7  (13.00) 36.1  (12.41) 39.0  (16.88) 37.4  (13.47)
[1]
Measure Analysis Population Description: All treated participants
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 80 participants 100 participants 51 participants 294 participants
Female
29
  46.0%
29
  36.3%
44
  44.0%
19
  37.3%
121
  41.2%
Male
34
  54.0%
51
  63.7%
56
  56.0%
32
  62.7%
173
  58.8%
[1]
Measure Analysis Population Description: All treated participants
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 80 participants 100 participants 51 participants 294 participants
Hispanic or Latino
3
   4.8%
1
   1.3%
1
   1.0%
0
   0.0%
5
   1.7%
Not Hispanic or Latino
30
  47.6%
63
  78.8%
56
  56.0%
40
  78.4%
189
  64.3%
Unknown or Not Reported
30
  47.6%
16
  20.0%
43
  43.0%
11
  21.6%
100
  34.0%
[1]
Measure Analysis Population Description: All treated participants
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 63 participants 80 participants 100 participants 51 participants 294 participants
White 54 71 86 45 256
Black or African 2 4 6 2 14
Asian 3 1 5 2 11
American Indian or Alaska Native 0 0 2 0 2
Native Hawaiian or Other Pacific Islander 0 0 0 0 0
Other 4 4 1 2 11
[1]
Measure Analysis Population Description: All treated particpants
1.Primary Outcome
Title Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C
Hide Description

ORR is the percent of participants achieving either a complete remission (CR) or partial remission (PR) according to the 2007 IWG criteria. Analyses of efficacy endpoints were performed separately for each cohort, according to IWG 2007. For cohort A and B, if the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. For cohort C, no evidence of FDG-avid disease in bone marrow was required in all participants in lieu of bone marrow aspirate/ biopsy.

CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment.

PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment.

Confidence interval based on Clopper-Pearson method.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurred first (up to approximately 28 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated Cohort A, B and C participants
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant
Hide Arm/Group Description:
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 63 80 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Particpants
65.1
(52.0 to 76.7)
67.5
(56.1 to 77.6)
73.0
(63.2 to 81.4)
2.Primary Outcome
Title Number of Participants Who Experienced at Least One Treatment Related Grade 3-5 AE in Cohort D
Hide Description An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
Time Frame From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Cohort D participants treated in the monotherapy and combination therapy phases.
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
Monotherapy Number Analyzed 51 participants
0
   0.0%
Combination Therapy (receiving AVD or NAVD) Number Analyzed 50 participants
30
  60.0%
3.Secondary Outcome
Title Duration of Objective Response Based on IRRC Assessments in Cohorts A, B, and C
Hide Description

DOR is the time from first response (complete remission (CR) or partial remission (PR)) to the date of initial objectively documented progression as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. For participants who neither progressed nor died, the DOR was censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy.

CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment.

PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment.

Computed using Kaplan-Meier method.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All treated Cohort A, B and C participants with objective response of CR or PR.
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant
Hide Arm/Group Description:
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 41 57 75
Median (95% Confidence Interval)
Unit of Measure: Months
26.18 [1] 
(15.21 to NA)
16.59
(9.26 to 25.72)
18.17
(11.63 to 30.85)
[1]
The upper 95% confidence interval was not reached due to Insufficient number of participants with events to reach the threshold according to Kaplan-Meier methodology.
4.Secondary Outcome
Title Complete Remission (CR) Rate Based on IRRC Assessments in Cohorts A, B, and C
Hide Description

The CR rate was defined as the percent of participants with a BOR of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment.

Confidence interval based on Clopper-Pearson method.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated Cohort A, B and C participants
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant
Hide Arm/Group Description:
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 63 80 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
31.7
(20.6 to 44.7)
13.8
(7.1 to 23.3)
21
(13.5 to 30.3)
5.Secondary Outcome
Title Duration of Complete Remission (CR) Based on IRRC Assessments for Cohorts A, B, and C
Hide Description

The duration of CR was only evaluated in participants with BOR of CR and was defined as the time from first documentation of CR (the date of first negative FDG-PET scan or the date of first documentation of no disease involvement in the bone marrow (if required), whichever occurred later) to the date of initial objectively documented progression (Any new lesion or increase by >=50% of previously involved sites from nadir) as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition.

Computed using Kaplan-Meier method.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated Cohort A, B and C participants who had a BOR of CR.
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant
Hide Arm/Group Description:
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 20 11 21
Median (95% Confidence Interval)
Unit of Measure: Months
43.47 [1] 
(18.00 to NA)
30.32 [1] 
(2.4 to NA)
26.41 [1] 
(7.13 to NA)
[1]
The upper 95% confidence interval was not reached due to Insufficient number of participants with events to reach the threshold according to Kaplan-Meier methodology.
6.Secondary Outcome
Title Partial Remission (PR) Rate Based on IRRC Assessments in Cohorts A, B, and C
Hide Description

The PR rate was defined as the percent of participants with a BOR of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment.

Confidence interval based on Clopper-Pearson method.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated Cohort A, B and C participants
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant
Hide Arm/Group Description:
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 63 80 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
33.3
(22.0 to 46.3)
57.5
(45.9 to 68.5)
54.0
(43.7 to 64.0)
7.Secondary Outcome
Title Duration of PR Based on IRRC Assessments in Cohorts A, B, and C
Hide Description

The duration of PR was only evaluated in participants with BOR of PR and was defined as the time from first documentation of PR (regression of measurable disease and no new sites) to the date of initial objectively documented progression (any new lesion or increase by >=50% of previously involved sites from nadir) as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition.

Computed using Kaplan-Meier method.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated Cohort A, B and C participants who had a BOR of PR.
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant
Hide Arm/Group Description:
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 21 46 54
Median (95% Confidence Interval)
Unit of Measure: Months
12.78
(4.17 to 27.17)
10.58
(7.46 to 25.26)
14.65
(9.36 to 30.36)
8.Secondary Outcome
Title Objective Response Rates (ORR) Based on Investigator Assessments for Cohorts A, B, and C
Hide Description

ORR is the percent of participants achieving either a complete remission (CR) or partial remission (PR) according to the 2007 IWG criteria. Analyses of efficacy endpoints were performed separately for each cohort, according to IWG 2007. For cohort A and B, if the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. For cohort C, no evidence of FDG-avid disease in bone marrow was required in all participants in lieu of bone marrow aspirate/ biopsy.

CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment.

PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment.

Confidence interval based on Clopper-Pearson method.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated Cohort A, B and C participants
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant
Hide Arm/Group Description:
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 63 80 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
69.8
(57.0 to 80.8)
73.8
(62.7 to 83.0)
70.0
(60.0 to 78.8)
9.Secondary Outcome
Title Duration of Objective Response (DOR) Based on Investigator Assessments in Cohorts A, B, and C
Hide Description

DOR is the time from first response (complete remission (CR) or partial remission (PR)) to the date of initial objectively documented progression as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. For participants who neither progressed nor died, the DOR was censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy.

CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment.

PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment.

Computed using Kaplan-Meier method.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
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Hide Analysis Population Description
All treated Cohort A, B and C participants who had a BOR of CR or PR.
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant
Hide Arm/Group Description:
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 44 59 70
Median (95% Confidence Interval)
Unit of Measure: Months
39.10
(16.59 to 78.29)
25.26
(10.09 to 41.72)
28.85
(12.02 to 34.53)
10.Secondary Outcome
Title Treatment Discontinuation Rate in Cohort D
Hide Description

Treatment discontinuation rate (TDR) is the number of treated participants who received <4 doses of monotherapy or <12 doses of their assigned combination regimen. A participant is considered as having received an AVD/NAVD dose as soon as they received at least one drug of AVD/NAVD for the considered dose. Participants must have received at least one dose of Nivolumab during the combination therapy phase to be included in participants treated with NAVD. If a participant subsequently met Criteria to Resume Nivolumab Dosing, the combination of nivolumab and AVD could be used. Participants who underwent treatment beyond progression during the Monotherapy phase could use the combination of nivolumab and AVD if all 4 doses of nivolumab monotherapy are completed.

Discontinuation can be due to any reason including, but not limited to, drug-related toxicity, diseases progression, or death.
Time Frame From first dose up until the date of treatment discontinuation (up to approximately 100 months).
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Hide Analysis Population Description
All Cohort D participants treated in the monotherapy and combination therapy phases.
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
Monotherapy Number Analyzed 51 participants
2
   3.9%
Combination Therapy (receiving AVD or NAVD) Number Analyzed 50 participants
5
  10.0%
Combination Therapy (NAVD receivers only) Number Analyzed 49 participants
5
  10.2%
Overall Therapy Number Analyzed 51 participants
6
  11.8%
11.Secondary Outcome
Title Number of Participants Who Died in Cohort D
Hide Description Number of participants who died in Cohort D within 100 days after last dose of study therapy.
Time Frame From first dose of the considered therapy phase to 100 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 10 months up to a maximum of 13 months)
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Hide Analysis Population Description
All Cohort D participants treated in the monotherapy and combination therapy phases.
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
Monotherapy Number Analyzed 51 participants
0
   0.0%
Combination Therapy (receiving AVD or NAVD) Number Analyzed 50 participants
1
   2.0%
12.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) in Cohort D
Hide Description An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort D
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
Monotherapy Number Analyzed 51 participants
48
  94.1%
Combination Therapy (receiving AVD or NAVD) Number Analyzed 50 participants
49
  98.0%
13.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) in Cohort D
Hide Description A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort D
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
Monotherapy Number Analyzed 51 participants
2
   3.9%
Combination Therapy (receiving AVD or NAVD) Number Analyzed 50 participants
10
  20.0%
14.Secondary Outcome
Title Number of Participants With AEs Leading to Discontinuation in Cohort D
Hide Description An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort D
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
Monotherapy Number Analyzed 51 participants
1
   2.0%
Combination Therapy (receiving AVD or NAVD) Number Analyzed 50 participants
3
   6.0%
15.Secondary Outcome
Title Number of Participants With AEs Leading to Dose Delay in Cohort D
Hide Description An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort D
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
Monotherapy Number Analyzed 51 participants
3
   5.9%
Combination Therapy (receiving AVD or NAVD) Number Analyzed 50 participants
29
  58.0%
16.Secondary Outcome
Title Number of Participants With Select AEs in Cohort D
Hide Description An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Select AEs have been categorized into seven areas: pulmonary toxicity, gastrointestinal toxicity, hepatotoxicity, endocrinopathy, skin toxicity, neurological toxicity and renal toxicity. Select AEs, in particular pneumonitis, are considered clinically meaningful as they require greater vigilance and for early recognition and prompt intervention.
Time Frame From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort D
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
Gastrointestinal Monotherapy
6
  11.8%
Gastrointestinal Combination Therapy
13
  25.5%
Hepatic Monotherapy
2
   3.9%
Hepatic Combination Therapy
3
   5.9%
Pulmonary Monotherapy
0
   0.0%
Pulmonary Combination Therapy
3
   5.9%
Renal Monotherapy
1
   2.0%
Renal Combination Therapy
0
   0.0%
Skin Monotherapy
17
  33.3%
Skin Combination Therapy
9
  17.6%
Hypersensitivity/Infusion Reactions Monotherapy
16
  31.4%
Hypersensitivity/Infusion Reactions Combination
4
   7.8%
17.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase
Hide Description The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
Time Frame From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months)
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Hide Analysis Population Description
All participants treated in the Cohort D monotherapy phase who had at least one on-treatment TSH measurement during the monotherapy phase
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 42
Measure Type: Count of Participants
Unit of Measure: Participants
TSH > ULN
1
   2.4%
TSH > ULN WITH TSH <= ULN AT BASELINE
1
   2.4%
TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN
0
   0.0%
TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN
0
   0.0%
TSH > ULN WITH FT3/FT4 TEST MISSING
1
   2.4%
TSH < LLN
5
  11.9%
TSH <LLN WITH TSH >= LLN AT BASELINE
5
  11.9%
TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN
1
   2.4%
TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN
0
   0.0%
TSH < LLN WITH FT3/FT4 TEST MISSING
4
   9.5%
18.Secondary Outcome
Title Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase
Hide Description The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
Time Frame From first dose of the combination therapy to 30 days after last dose of combination therapy (an average of 8 months and a maximum of 11 months)
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Hide Analysis Population Description
All participants treated in the Cohort D combination therapy phase who had at least one on-treatment AST, ALT and/or bilirubin test measurement during the combination therapy phase
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 48
Measure Type: Count of Participants
Unit of Measure: Participants
TSH > ULN
12
  25.0%
TSH > ULN WITH TSH <= ULN AT BASELINE
8
  16.7%
TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN
3
   6.3%
TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN
1
   2.1%
TSH > ULN WITH FT3/FT4 TEST MISSING
8
  16.7%
TSH < LLN
5
  10.4%
TSH <LLN WITH TSH >= LLN AT BASELINE
5
  10.4%
TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN
1
   2.1%
TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN
0
   0.0%
TSH < LLN WITH FT3/FT4 TEST MISSING
4
   8.3%
19.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase
Hide Description The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase, ULN = Upper Limit of Normal.
Time Frame From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in the Cohort D monotherapy phase
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Count of Participants
Unit of Measure: Participants
ALT OR AST > 3XULN
2
   3.9%
ALT OR AST> 5XULN
1
   2.0%
ALT OR AST> 10XULN
0
   0.0%
ALT OR AST > 20XULN
0
   0.0%
TOTAL BILIRUBIN > 2XULN
0
   0.0%
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY
0
   0.0%
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS
0
   0.0%
20.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase
Hide Description The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase, ULN = Upper Limit of Normal.
Time Frame From first dose of the combination therapy to 30 days after last dose of combination therapy (an average of 8 months and a maximum of 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in the Cohort D combination therapy phase with at least one on-treatment laboratory measurement
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 49
Measure Type: Count of Participants
Unit of Measure: Participants
ALT OR AST > 3XULN
4
   8.2%
ALT OR AST> 5XULN
1
   2.0%
ALT OR AST> 10XULN
1
   2.0%
ALT OR AST > 20XULN
0
   0.0%
TOTAL BILIRUBIN > 2XULN
0
   0.0%
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY
0
   0.0%
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS
0
   0.0%
21.Secondary Outcome
Title Complete Response (CR) Rate at Planned End of Therapy Based on IRRC Assessments in Cohort D
Hide Description

CR rate is the percent of participants who show CR (disappearance of all evidence of disease) according to the 2007 IWG criteria at the planned end of study therapy radiographic tumor assessment.

Confidence interval based on the Klopper and Pearson method.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
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Hide Analysis Population Description
All Cohort D participants treated in the monotherapy and combination therapy phases.
Arm/Group Title Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description:
Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
Overall Number of Participants Analyzed 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
66.7
(52.1 to 79.2)
22.Post-Hoc Outcome
Title Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C Extended Collection
Hide Description Represents an updated version of the primary endpoint to include additional data collection that occurred after the primary completion date. (Assessments were made until 30 Nov 2022). Clinical benefit of nivolumab, as measured by ORR per IRRC assessment, and defined as percent of participants achieving either complete remission (CR) or partial remission (PR) according to the 2007 IWG criteria. For cohort A and B, if the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. For cohort C, no evidence of FDG-avid disease in bone marrow was required in all patients in lieu of bone marrow aspirate/ biopsy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria.
Time Frame From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurred first (up to approximately 100 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated Cohort A, B and C participants
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant
Hide Arm/Group Description:
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 63 80 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
65.1
(52.0 to 76.7)
71.3
(60.0 to 80.8)
75.0
(65.3 to 83.1)
Time Frame Participants were assessed for All-Cause Mortality from first dose until study completion (assessed up to approximately 100 months). SAEs and Other AEs were assessed from first dose to 100 days after last dose of study therapy (assessed for an average of 32 months up to maximum of 98 months).
Adverse Event Reporting Description

All-Cause Mortality and Serious and Other (Not Including Serious) Adverse Events is represented per dosage, per arm for Cohorts A, B, and C. This is to account for these events after the dosage and administration changes for nivolumab were implemented per revised protocol version 04c (dated 22-Aug-2019).

Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
 
Arm/Group Title Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin- Nivolumab 3 mg/kg Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin-Nivolumab 240 mg Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin-Nivolumab 480 mg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant-Nivolumab 3 mg/kg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant-Nivolumab 240 mg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant- Nivolumab 480 mg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/or Post-SC Transplant - Nivolumab 3 mg/kg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/Post-Stem Cell Transplant - Nivolumab 240 mg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/Post-Stem Cell Transplant - Nivolumab 480 mg Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
Hide Arm/Group Description Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase).
All-Cause Mortality
Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin- Nivolumab 3 mg/kg Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin-Nivolumab 240 mg Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin-Nivolumab 480 mg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant-Nivolumab 3 mg/kg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant-Nivolumab 240 mg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant- Nivolumab 480 mg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/or Post-SC Transplant - Nivolumab 3 mg/kg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/Post-Stem Cell Transplant - Nivolumab 240 mg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/Post-Stem Cell Transplant - Nivolumab 480 mg Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
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   14/46 (30.43%)   3/9 (33.33%)   0/8 (0.00%)   25/75 (33.33%)   0/3 (0.00%)   0/2 (0.00%)   31/84 (36.90%)   4/13 (30.77%)   0/3 (0.00%)   5/51 (9.80%) 
Hide Serious Adverse Events
Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin- Nivolumab 3 mg/kg Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin-Nivolumab 240 mg Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin-Nivolumab 480 mg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant-Nivolumab 3 mg/kg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant-Nivolumab 240 mg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant- Nivolumab 480 mg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/or Post-SC Transplant - Nivolumab 3 mg/kg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/Post-Stem Cell Transplant - Nivolumab 240 mg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/Post-Stem Cell Transplant - Nivolumab 480 mg Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
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   10/46 (21.74%)   3/9 (33.33%)   1/8 (12.50%)   30/75 (40.00%)   0/3 (0.00%)   1/2 (50.00%)   33/84 (39.29%)   8/13 (61.54%)   3/3 (100.00%)   12/51 (23.53%) 
Blood and lymphatic system disorders                     
Anaemia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Febrile neutropenia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Cardiac disorders                     
Acute myocardial infarction † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Angina pectoris † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Arrhythmia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Cardiac arrest † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Cardiac failure † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Cardiac failure congestive † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Myocardial infarction † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Palpitations † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pericardial effusion † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Congenital, familial and genetic disorders                     
Tracheo-oesophageal fistula † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Endocrine disorders                     
Hyperthyroidism † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Gastrointestinal disorders                     
Abdominal pain † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Colitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
Diarrhoea † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Enteritis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Gastritis † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Immune-mediated enterocolitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Nausea † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pancreatitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Stomatitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Vomiting † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
General disorders                     
Fatigue † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Generalised oedema † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Multiple organ dysfunction syndrome † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pyrexia † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  1/2 (50.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Systemic inflammatory response syndrome † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Hepatobiliary disorders                     
Autoimmune hepatitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Cholelithiasis † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Hyperbilirubinaemia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Immune system disorders                     
Acute graft versus host disease † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Graft versus host disease † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Infections and infestations                     
Appendicitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Atypical pneumonia † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Bacteraemia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Bacterial sepsis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Cellulitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Cystitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Device related sepsis † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Encephalitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Erysipelas † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Febrile infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Gastroenteritis † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Hepatitis A † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Influenza † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Lower respiratory tract infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Lyme disease † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Meningitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Nasopharyngitis † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Parainfluenzae virus infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pharyngitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Pneumocystis jirovecii pneumonia † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pneumonia † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  5/75 (6.67%)  0/3 (0.00%)  0/2 (0.00%)  5/84 (5.95%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Pyelonephritis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Respiratory tract infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  1/51 (1.96%) 
Sepsis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Upper respiratory tract infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Urinary tract infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Injury, poisoning and procedural complications                     
Infusion related reaction † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Muscle rupture † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Spinal compression fracture † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Investigations                     
Alanine aminotransferase increased † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
Aspartate aminotransferase increased † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Blood creatine phosphokinase increased † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Blood creatinine increased † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Lipase increased † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Platelet count decreased † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Respirovirus test positive † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Metabolism and nutrition disorders                     
Dehydration † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Diabetic ketoacidosis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Glucose tolerance impaired † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Hypercalcaemia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Hypokalaemia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Hyponatraemia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Back pain † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Bone pain † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Bursitis † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Myalgia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Osteonecrosis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pain in extremity † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Polyarthritis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Soft tissue disorder † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                     
Basal cell carcinoma † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Breast cancer † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Follicular lymphoma stage III † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Gastrointestinal stromal tumour † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Malignant neoplasm progression † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Neuroendocrine carcinoma of the skin † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Peripheral T-cell lymphoma unspecified † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Squamous cell carcinoma of the tongue † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Nervous system disorders                     
Carotid artery stenosis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Guillain-Barre syndrome † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Headache † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Polyneuropathy † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Posterior reversible encephalopathy syndrome † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Seizure † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Syncope † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pregnancy, puerperium and perinatal conditions                     
Pregnancy † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Psychiatric disorders                     
Suicide attempt † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Renal and urinary disorders                     
Acute kidney injury † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Tubulointerstitial nephritis † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Reproductive system and breast disorders                     
Ovarian cyst † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Acute respiratory failure † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Dyspnoea † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Haemoptysis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Pleural effusion † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pneumonitis † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Pneumothorax † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pulmonary embolism † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Tracheomalacia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Skin and subcutaneous tissue disorders                     
Pruritus † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Rash † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Rash maculo-papular † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Vascular disorders                     
Embolism † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Peripheral ischaemia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
1
Term from vocabulary, 25.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin- Nivolumab 3 mg/kg Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin-Nivolumab 240 mg Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin-Nivolumab 480 mg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant-Nivolumab 3 mg/kg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant-Nivolumab 240 mg Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Stem Cell Transplant- Nivolumab 480 mg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/or Post-SC Transplant - Nivolumab 3 mg/kg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/Post-Stem Cell Transplant - Nivolumab 240 mg Cohort C: Post Transplant, Brentuximab Vedotin Pre-and/Post-Stem Cell Transplant - Nivolumab 480 mg Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV)
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   46/46 (100.00%)   9/9 (100.00%)   8/8 (100.00%)   75/75 (100.00%)   3/3 (100.00%)   2/2 (100.00%)   80/84 (95.24%)   13/13 (100.00%)   3/3 (100.00%)   50/51 (98.04%) 
Blood and lymphatic system disorders                     
Anaemia † 1  4/46 (8.70%)  1/9 (11.11%)  1/8 (12.50%)  12/75 (16.00%)  0/3 (0.00%)  0/2 (0.00%)  18/84 (21.43%)  2/13 (15.38%)  0/3 (0.00%)  9/51 (17.65%) 
Eosinophilia † 1  1/46 (2.17%)  0/9 (0.00%)  1/8 (12.50%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Febrile neutropenia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  4/51 (7.84%) 
Leukopenia † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
Neutropenia † 1  4/46 (8.70%)  1/9 (11.11%)  0/8 (0.00%)  7/75 (9.33%)  0/3 (0.00%)  0/2 (0.00%)  9/84 (10.71%)  2/13 (15.38%)  0/3 (0.00%)  28/51 (54.90%) 
Thrombocytopenia † 1  3/46 (6.52%)  0/9 (0.00%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  14/84 (16.67%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Cardiac disorders                     
Palpitations † 1  3/46 (6.52%)  0/9 (0.00%)  1/8 (12.50%)  1/75 (1.33%)  1/3 (33.33%)  0/2 (0.00%)  3/84 (3.57%)  1/13 (7.69%)  0/3 (0.00%)  2/51 (3.92%) 
Tachycardia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  7/75 (9.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Ear and labyrinth disorders                     
Ear pain † 1  1/46 (2.17%)  0/9 (0.00%)  1/8 (12.50%)  4/75 (5.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Tinnitus † 1  3/46 (6.52%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  1/2 (50.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Vertigo † 1  1/46 (2.17%)  1/9 (11.11%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Endocrine disorders                     
Hyperthyroidism † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Hypothyroidism † 1  7/46 (15.22%)  1/9 (11.11%)  1/8 (12.50%)  9/75 (12.00%)  0/3 (0.00%)  0/2 (0.00%)  7/84 (8.33%)  2/13 (15.38%)  0/3 (0.00%)  8/51 (15.69%) 
Primary hypothyroidism † 1  1/46 (2.17%)  0/9 (0.00%)  1/8 (12.50%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  1/13 (7.69%)  1/3 (33.33%)  0/51 (0.00%) 
Eye disorders                     
Dry eye † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  3/75 (4.00%)  1/3 (33.33%)  0/2 (0.00%)  7/84 (8.33%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Eye disorder † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  1/2 (50.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Eye pruritus † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Mydriasis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Swelling of eyelid † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
Vision blurred † 1  3/46 (6.52%)  1/9 (11.11%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  0/13 (0.00%)  1/3 (33.33%)  4/51 (7.84%) 
Visual field defect † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Vitreous floaters † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Gastrointestinal disorders                     
Abdominal discomfort † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Abdominal distension † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Abdominal hernia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Abdominal pain † 1  7/46 (15.22%)  1/9 (11.11%)  0/8 (0.00%)  14/75 (18.67%)  2/3 (66.67%)  1/2 (50.00%)  13/84 (15.48%)  0/13 (0.00%)  0/3 (0.00%)  4/51 (7.84%) 
Abdominal pain upper † 1  6/46 (13.04%)  3/9 (33.33%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Anorectal discomfort † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Constipation † 1  7/46 (15.22%)  2/9 (22.22%)  1/8 (12.50%)  14/75 (18.67%)  1/3 (33.33%)  1/2 (50.00%)  15/84 (17.86%)  0/13 (0.00%)  1/3 (33.33%)  18/51 (35.29%) 
Diarrhoea † 1  26/46 (56.52%)  3/9 (33.33%)  5/8 (62.50%)  37/75 (49.33%)  1/3 (33.33%)  2/2 (100.00%)  25/84 (29.76%)  6/13 (46.15%)  1/3 (33.33%)  17/51 (33.33%) 
Dry mouth † 1  2/46 (4.35%)  0/9 (0.00%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  1/13 (7.69%)  1/3 (33.33%)  3/51 (5.88%) 
Dyspepsia † 1  4/46 (8.70%)  0/9 (0.00%)  1/8 (12.50%)  5/75 (6.67%)  0/3 (0.00%)  0/2 (0.00%)  5/84 (5.95%)  0/13 (0.00%)  1/3 (33.33%)  4/51 (7.84%) 
Dysphagia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  5/75 (6.67%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Flatulence † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Gastritis † 1  3/46 (6.52%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Gastrooesophageal reflux disease † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  7/75 (9.33%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Haemorrhoids † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Nausea † 1  14/46 (30.43%)  1/9 (11.11%)  5/8 (62.50%)  20/75 (26.67%)  1/3 (33.33%)  1/2 (50.00%)  19/84 (22.62%)  1/13 (7.69%)  1/3 (33.33%)  31/51 (60.78%) 
Pancreatitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  1/2 (50.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Periodontal disease † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Steatorrhoea † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Stomatitis † 1  5/46 (10.87%)  0/9 (0.00%)  1/8 (12.50%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  0/13 (0.00%)  0/3 (0.00%)  12/51 (23.53%) 
Toothache † 1  2/46 (4.35%)  1/9 (11.11%)  1/8 (12.50%)  5/75 (6.67%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  0/13 (0.00%)  1/3 (33.33%)  3/51 (5.88%) 
Vomiting † 1  11/46 (23.91%)  2/9 (22.22%)  5/8 (62.50%)  18/75 (24.00%)  0/3 (0.00%)  1/2 (50.00%)  19/84 (22.62%)  1/13 (7.69%)  1/3 (33.33%)  15/51 (29.41%) 
General disorders                     
Asthenia † 1  4/46 (8.70%)  1/9 (11.11%)  2/8 (25.00%)  9/75 (12.00%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  1/13 (7.69%)  0/3 (0.00%)  7/51 (13.73%) 
Chest discomfort † 1  2/46 (4.35%)  1/9 (11.11%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Chest pain † 1  1/46 (2.17%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  1/13 (7.69%)  0/3 (0.00%)  4/51 (7.84%) 
Chills † 1  2/46 (4.35%)  3/9 (33.33%)  1/8 (12.50%)  4/75 (5.33%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  3/13 (23.08%)  0/3 (0.00%)  6/51 (11.76%) 
Fatigue † 1  19/46 (41.30%)  5/9 (55.56%)  3/8 (37.50%)  36/75 (48.00%)  1/3 (33.33%)  2/2 (100.00%)  27/84 (32.14%)  2/13 (15.38%)  2/3 (66.67%)  19/51 (37.25%) 
Feeling cold † 1  0/46 (0.00%)  2/9 (22.22%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Illness † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Inflammation † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Influenza like illness † 1  2/46 (4.35%)  0/9 (0.00%)  3/8 (37.50%)  5/75 (6.67%)  2/3 (66.67%)  1/2 (50.00%)  2/84 (2.38%)  1/13 (7.69%)  2/3 (66.67%)  0/51 (0.00%) 
Malaise † 1  1/46 (2.17%)  2/9 (22.22%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Mucosal dryness † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Mucosal inflammation † 1  4/46 (8.70%)  1/9 (11.11%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  1/13 (7.69%)  1/3 (33.33%)  5/51 (9.80%) 
Non-cardiac chest pain † 1  1/46 (2.17%)  0/9 (0.00%)  1/8 (12.50%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Oedema peripheral † 1  2/46 (4.35%)  0/9 (0.00%)  0/8 (0.00%)  6/75 (8.00%)  0/3 (0.00%)  0/2 (0.00%)  11/84 (13.10%)  1/13 (7.69%)  0/3 (0.00%)  2/51 (3.92%) 
Pain † 1  2/46 (4.35%)  0/9 (0.00%)  0/8 (0.00%)  6/75 (8.00%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Peripheral swelling † 1  1/46 (2.17%)  0/9 (0.00%)  2/8 (25.00%)  4/75 (5.33%)  1/3 (33.33%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pyrexia † 1  12/46 (26.09%)  5/9 (55.56%)  3/8 (37.50%)  33/75 (44.00%)  1/3 (33.33%)  2/2 (100.00%)  29/84 (34.52%)  2/13 (15.38%)  1/3 (33.33%)  20/51 (39.22%) 
Thirst † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Hepatobiliary disorders                     
Hepatic steatosis † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Venoocclusive liver disease † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Immune system disorders                     
Anaphylactic reaction † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Cytokine release syndrome † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Hypersensitivity † 1  2/46 (4.35%)  1/9 (11.11%)  2/8 (25.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Seasonal allergy † 1  3/46 (6.52%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Infections and infestations                     
Aeromonas infection † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Atypical mycobacterial infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Bacterial infection † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Bronchitis † 1  2/46 (4.35%)  2/9 (22.22%)  3/8 (37.50%)  6/75 (8.00%)  0/3 (0.00%)  1/2 (50.00%)  2/84 (2.38%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
COVID-19 † 1  1/46 (2.17%)  0/9 (0.00%)  2/8 (25.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Cellulitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  5/75 (6.67%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Conjunctivitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  4/75 (5.33%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
Cystitis † 1  2/46 (4.35%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Folliculitis † 1  3/46 (6.52%)  0/9 (0.00%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
Gastric infection † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Gastroenteritis † 1  2/46 (4.35%)  0/9 (0.00%)  1/8 (12.50%)  3/75 (4.00%)  1/3 (33.33%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Gastrointestinal infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  5/75 (6.67%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Gingivitis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Herpes simplex † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Herpes zoster † 1  4/46 (8.70%)  0/9 (0.00%)  2/8 (25.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  2/13 (15.38%)  0/3 (0.00%)  0/51 (0.00%) 
Hordeolum † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Infected skin ulcer † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Infection † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Influenza † 1  2/46 (4.35%)  3/9 (33.33%)  0/8 (0.00%)  5/75 (6.67%)  0/3 (0.00%)  0/2 (0.00%)  5/84 (5.95%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
Lip infection † 1  0/46 (0.00%)  0/9 (0.00%)  2/8 (25.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Lymph gland infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Nasopharyngitis † 1  10/46 (21.74%)  5/9 (55.56%)  6/8 (75.00%)  21/75 (28.00%)  3/3 (100.00%)  1/2 (50.00%)  10/84 (11.90%)  3/13 (23.08%)  2/3 (66.67%)  6/51 (11.76%) 
Oral herpes † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  1/13 (7.69%)  2/3 (66.67%)  1/51 (1.96%) 
Pharyngitis † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Pharyngitis bacterial † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Pneumonia † 1  4/46 (8.70%)  1/9 (11.11%)  1/8 (12.50%)  13/75 (17.33%)  2/3 (66.67%)  1/2 (50.00%)  6/84 (7.14%)  1/13 (7.69%)  1/3 (33.33%)  3/51 (5.88%) 
Pyelonephritis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Respiratory tract infection † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  4/75 (5.33%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  1/13 (7.69%)  0/3 (0.00%)  3/51 (5.88%) 
Rhinitis † 1  1/46 (2.17%)  3/9 (33.33%)  1/8 (12.50%)  6/75 (8.00%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Septic shock † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Sinusitis † 1  2/46 (4.35%)  3/9 (33.33%)  1/8 (12.50%)  6/75 (8.00%)  0/3 (0.00%)  1/2 (50.00%)  4/84 (4.76%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Skin infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
Tooth abscess † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Tooth infection † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Upper respiratory tract infection † 1  11/46 (23.91%)  1/9 (11.11%)  3/8 (37.50%)  28/75 (37.33%)  1/3 (33.33%)  0/2 (0.00%)  18/84 (21.43%)  3/13 (23.08%)  0/3 (0.00%)  6/51 (11.76%) 
Urinary tract infection † 1  3/46 (6.52%)  0/9 (0.00%)  1/8 (12.50%)  7/75 (9.33%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  1/13 (7.69%)  1/3 (33.33%)  1/51 (1.96%) 
Viral infection † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  5/75 (6.67%)  2/3 (66.67%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Viral upper respiratory tract infection † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  2/13 (15.38%)  0/3 (0.00%)  0/51 (0.00%) 
Injury, poisoning and procedural complications                     
Ankle fracture † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Arthropod bite † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Compression fracture † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Contusion † 1  1/46 (2.17%)  0/9 (0.00%)  1/8 (12.50%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Fall † 1  1/46 (2.17%)  1/9 (11.11%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Infusion related reaction † 1  6/46 (13.04%)  0/9 (0.00%)  0/8 (0.00%)  13/75 (17.33%)  1/3 (33.33%)  1/2 (50.00%)  9/84 (10.71%)  1/13 (7.69%)  1/3 (33.33%)  16/51 (31.37%) 
Ligament sprain † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  1/2 (50.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Pelvic fracture † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Post-traumatic pain † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Skin laceration † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  1/3 (33.33%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Skin procedural complication † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Sunburn † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Wrist fracture † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Investigations                     
Alanine aminotransferase increased † 1  6/46 (13.04%)  2/9 (22.22%)  2/8 (25.00%)  11/75 (14.67%)  0/3 (0.00%)  0/2 (0.00%)  9/84 (10.71%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Amylase increased † 1  2/46 (4.35%)  1/9 (11.11%)  0/8 (0.00%)  7/75 (9.33%)  0/3 (0.00%)  1/2 (50.00%)  3/84 (3.57%)  1/13 (7.69%)  0/3 (0.00%)  3/51 (5.88%) 
Aspartate aminotransferase increased † 1  4/46 (8.70%)  1/9 (11.11%)  2/8 (25.00%)  9/75 (12.00%)  0/3 (0.00%)  0/2 (0.00%)  10/84 (11.90%)  0/13 (0.00%)  1/3 (33.33%)  2/51 (3.92%) 
Blood alkaline phosphatase increased † 1  2/46 (4.35%)  1/9 (11.11%)  0/8 (0.00%)  6/75 (8.00%)  0/3 (0.00%)  0/2 (0.00%)  8/84 (9.52%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Blood bilirubin increased † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  4/75 (5.33%)  0/3 (0.00%)  1/2 (50.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Blood creatinine increased † 1  1/46 (2.17%)  1/9 (11.11%)  0/8 (0.00%)  6/75 (8.00%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Blood thyroid stimulating hormone increased † 1  1/46 (2.17%)  1/9 (11.11%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  1/13 (7.69%)  1/3 (33.33%)  1/51 (1.96%) 
Gamma-glutamyltransferase increased † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Lipase increased † 1  4/46 (8.70%)  1/9 (11.11%)  1/8 (12.50%)  16/75 (21.33%)  0/3 (0.00%)  1/2 (50.00%)  4/84 (4.76%)  1/13 (7.69%)  1/3 (33.33%)  2/51 (3.92%) 
Liver function test increased † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Lymphocyte count decreased † 1  2/46 (4.35%)  0/9 (0.00%)  0/8 (0.00%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  5/84 (5.95%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Neutrophil count decreased † 1  0/46 (0.00%)  0/9 (0.00%)  2/8 (25.00%)  4/75 (5.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  10/51 (19.61%) 
Platelet count decreased † 1  5/46 (10.87%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  1/3 (33.33%)  0/2 (0.00%)  3/84 (3.57%)  2/13 (15.38%)  0/3 (0.00%)  1/51 (1.96%) 
SARS-CoV-2 test positive † 1  0/46 (0.00%)  1/9 (11.11%)  1/8 (12.50%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Sputum abnormal † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Transaminases increased † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Weight decreased † 1  3/46 (6.52%)  0/9 (0.00%)  3/8 (37.50%)  6/75 (8.00%)  0/3 (0.00%)  1/2 (50.00%)  4/84 (4.76%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Weight increased † 1  3/46 (6.52%)  1/9 (11.11%)  1/8 (12.50%)  7/75 (9.33%)  0/3 (0.00%)  1/2 (50.00%)  8/84 (9.52%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
White blood cell count decreased † 1  3/46 (6.52%)  0/9 (0.00%)  1/8 (12.50%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  9/51 (17.65%) 
Metabolism and nutrition disorders                     
Decreased appetite † 1  5/46 (10.87%)  3/9 (33.33%)  2/8 (25.00%)  11/75 (14.67%)  0/3 (0.00%)  1/2 (50.00%)  7/84 (8.33%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Dehydration † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  1/3 (33.33%)  1/51 (1.96%) 
Hyperglycaemia † 1  3/46 (6.52%)  0/9 (0.00%)  0/8 (0.00%)  8/75 (10.67%)  0/3 (0.00%)  0/2 (0.00%)  7/84 (8.33%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Hypokalaemia † 1  3/46 (6.52%)  0/9 (0.00%)  0/8 (0.00%)  6/75 (8.00%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Hypomagnesaemia † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  5/75 (6.67%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  1/13 (7.69%)  0/3 (0.00%)  2/51 (3.92%) 
Hyponatraemia † 1  2/46 (4.35%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  6/84 (7.14%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Vitamin B12 deficiency † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Arthralgia † 1  9/46 (19.57%)  4/9 (44.44%)  2/8 (25.00%)  27/75 (36.00%)  1/3 (33.33%)  1/2 (50.00%)  15/84 (17.86%)  1/13 (7.69%)  1/3 (33.33%)  11/51 (21.57%) 
Back pain † 1  8/46 (17.39%)  1/9 (11.11%)  2/8 (25.00%)  17/75 (22.67%)  1/3 (33.33%)  1/2 (50.00%)  12/84 (14.29%)  0/13 (0.00%)  0/3 (0.00%)  8/51 (15.69%) 
Bone pain † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  1/3 (33.33%)  8/51 (15.69%) 
Flank pain † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Groin pain † 1  1/46 (2.17%)  2/9 (22.22%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Joint effusion † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  1/3 (33.33%)  1/2 (50.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Joint swelling † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  4/75 (5.33%)  1/3 (33.33%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  1/51 (1.96%) 
Muscle contracture † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Muscle spasms † 1  3/46 (6.52%)  0/9 (0.00%)  1/8 (12.50%)  11/75 (14.67%)  0/3 (0.00%)  0/2 (0.00%)  5/84 (5.95%)  1/13 (7.69%)  0/3 (0.00%)  1/51 (1.96%) 
Muscle swelling † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Musculoskeletal chest pain † 1  2/46 (4.35%)  1/9 (11.11%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  4/84 (4.76%)  0/13 (0.00%)  0/3 (0.00%)  2/51 (3.92%) 
Myalgia † 1  7/46 (15.22%)  1/9 (11.11%)  2/8 (25.00%)  11/75 (14.67%)  1/3 (33.33%)  1/2 (50.00%)  9/84 (10.71%)  0/13 (0.00%)  0/3 (0.00%)  7/51 (13.73%) 
Neck pain † 1  1/46 (2.17%)  0/9 (0.00%)  1/8 (12.50%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Osteoporosis † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Pain in extremity † 1  3/46 (6.52%)  1/9 (11.11%)  0/8 (0.00%)  6/75 (8.00%)  0/3 (0.00%)  0/2 (0.00%)  7/84 (8.33%)  1/13 (7.69%)  0/3 (0.00%)  3/51 (5.88%) 
Periarthritis † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Plantar fasciitis † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Spinal pain † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                     
Skin papilloma † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Tumour pain † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  1/75 (1.33%)  0/3 (0.00%)  1/2 (50.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Nervous system disorders                     
Cerebrospinal fluid leakage † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  1/3 (33.33%)  0/51 (0.00%) 
Convulsions local † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Dizziness † 1  6/46 (13.04%)  0/9 (0.00%)  1/8 (12.50%)  10/75 (13.33%)  1/3 (33.33%)  0/2 (0.00%)  7/84 (8.33%)  0/13 (0.00%)  0/3 (0.00%)  8/51 (15.69%) 
Dysaesthesia † 1  1/46 (2.17%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  1/13 (7.69%)  0/3 (0.00%)  0/51 (0.00%) 
Headache † 1  14/46 (30.43%)  3/9 (33.33%)  2/8 (25.00%)  15/75 (20.00%)  0/3 (0.00%)  0/2 (0.00%)  13/84 (15.48%)  3/13 (23.08%)  2/3 (66.67%)  7/51 (13.73%) 
Hypoaesthesia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  5/75 (6.67%)  0/3 (0.00%)  0/2 (0.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Lethargy † 1  1/46 (2.17%)  0/9 (0.00%)  1/8 (12.50%)  1/75 (1.33%)  0/3 (0.00%)  0/2 (0.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Memory impairment † 1  2/46 (4.35%)  0/9 (0.00%)  0/8 (0.00%)  2/75 (2.67%)  0/3 (0.00%)  0/2 (0.00%)  3/84 (3.57%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Migraine † 1  1/46 (2.17%)  1/9 (11.11%)  1/8 (12.50%)  3/75 (4.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Migraine with aura † 1  0/46 (0.00%)  1/9 (11.11%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%) 
Neuropathy peripheral † 1  3/46 (6.52%)  1/9 (11.11%)  0/8 (0.00%)  9/75 (12.00%)  0/3 (0.00%)  1/2 (50.00%)  3/84 (3.57%)  1/13 (7.69%)  0/3 (0.00%)  5/51 (9.80%) 
Peripheral sensory neuropathy † 1  0/46 (0.00%)  0/9 (0.00%)  1/8 (12.50%)  3/75 (4.00%)  0/3 (0.00%)  1/2 (50.00%)  2/84 (2.38%)  0/13 (0.00%)  0/3 (0.00%)  4/51 (7.84%) 
Polyneuropathy † 1  2/46 (4.35%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  0/2 (0.00%)  0/84 (0.00%)  0/13 (0.00%)  0/3 (0.00%)  3/51 (5.88%) 
Post herpetic neuralgia † 1  0/46 (0.00%)  0/9 (0.00%)  0/8 (0.00%)  0/75 (0.00%)  0/3 (0.00%)  1/2 (50.00%)  1/84 (1.19%)  0/13 (0.00%)  0/3 (0.00%)  0/51 (0.00%)