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A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03971422
Recruitment Status : Completed
First Posted : June 3, 2019
Results First Posted : August 21, 2023
Last Update Posted : September 5, 2023
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma SRL )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Generalized Myasthenia Gravis
Interventions Drug: Rozanolixizumab
Other: Placebo
Enrollment 200
Recruitment Details The study started to enroll study participants in Jun 2019 and concluded in Oct 2021.
Pre-assignment Details Participant Flow refers to the Randomized Set. Two participants randomized to RLZ ~7mg/kg, were administered RLZ ~10mg/kg at baseline visit. So, these two participants were included in RLZ ~7 mg/kg group in randomized set, but in RLZ ~10 mg/kg group in safety set.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14). Participants received rozanolixizumab (RLZ) equivalent to approximately 7 milligrams/kilogram (mg/kg), subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14). Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Period Title: Overall Study
Started 67 66 67
Completed 42 43 43
Not Completed 25 23 24
Reason Not Completed
Lost to Follow-up             0             1             0
Lack of Efficacy             5             1             1
Adverse event, not fatal             2             2             5
Worsening of MG Symptoms             1             4             2
Roll over to MG0007 (NCT04650854)             10             6             9
Roll over to MG0004 (NCT04124965)             7             8             6
Due to COVID-19 pandemic             0             1             1
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg Total
Hide Arm/Group Description Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14). Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14). Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14). Total of all reporting groups
Overall Number of Baseline Participants 67 66 67 200
Hide Baseline Analysis Population Description
Baseline Characteristics refers to the Randomized Set (RS) which consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 66 participants 67 participants 200 participants
<=18 years
1
   1.5%
0
   0.0%
0
   0.0%
1
   0.5%
Between 18 and 65 years
50
  74.6%
49
  74.2%
51
  76.1%
150
  75.0%
>=65 years
16
  23.9%
17
  25.8%
16
  23.9%
49
  24.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 67 participants 66 participants 67 participants 200 participants
50.4  (17.7) 53.2  (14.7) 51.9  (16.5) 51.8  (16.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 66 participants 67 participants 200 participants
Female
47
  70.1%
39
  59.1%
35
  52.2%
121
  60.5%
Male
20
  29.9%
27
  40.9%
32
  47.8%
79
  39.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 66 participants 67 participants 200 participants
Asian
5
   7.5%
9
  13.6%
7
  10.4%
21
  10.5%
Black
1
   1.5%
0
   0.0%
4
   6.0%
5
   2.5%
Native Hawaiian or other Pacific Islander
1
   1.5%
0
   0.0%
0
   0.0%
1
   0.5%
White
46
  68.7%
41
  62.1%
49
  73.1%
136
  68.0%
Missing
14
  20.9%
16
  24.2%
7
  10.4%
37
  18.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 66 participants 67 participants 200 participants
Hispanic or Latino
5
   7.5%
5
   7.6%
3
   4.5%
13
   6.5%
Not Hispanic or Latino
48
  71.6%
47
  71.2%
58
  86.6%
153
  76.5%
Missing
14
  20.9%
14
  21.2%
6
   9.0%
34
  17.0%
1.Primary Outcome
Title Change From Baseline to Day 43 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score
Hide Description The Myasthenia Gravis Activities of Daily Living (MG-ADL) is an 8-item patient-reported outcome (PRO) instrument developed on the basis of the Quantitative Myasthenia Gravis (QMG). The MG-ADL targeted symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The total MG-ADL score was obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3), where 0 represents no symptoms or impaired performance and 3 represents the most severe symptoms or impaired performance. The total score ranges from 0 to 24, with a higher score indicating more disability. A positive change in the score indicates worsening and a negative change indicates improvement.
Time Frame Baseline and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description:
Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Overall Number of Participants Analyzed 67 66 67
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.784  (0.488) -3.370  (0.486) -3.403  (0.494)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~7 mg/kg
Comments The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.586
Confidence Interval (2-Sided) 95%
-4.091 to -1.249
Estimation Comments Mixed model repeated measure (MMRM) ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~10 mg/kg
Comments The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.619
Confidence Interval (2-Sided) 95%
-3.994 to -1.163
Estimation Comments MMRM analysis of covariance (ANCOVA) model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
2.Secondary Outcome
Title Percentage of Participants Achieving Myasthenia Gravis-Activities of Daily Living (MG-ADL) Response at Day 43
Hide Description The MG-ADL is an 8-item PRO instrument developed on the basis of the QMG. The MG-ADL targeted symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The total MG-ADL score was obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3), where 0 represents no symptoms or impaired performance and 3 represents the most severe symptoms or impaired performance. The total score ranges from 0 to 24, with a higher score indicating more disability. A positive change in the score indicates worsening and a negative change indicates improvement. Study participants were classified as responders at Day 43 if the value was at least a 2-point improvement (decrease) from Baseline at Day 43.
Time Frame Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description:
Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Overall Number of Participants Analyzed 67 66 67
Measure Type: Number
Unit of Measure: percentage of participants
28.4 68.2 61.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~7 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is nominal. Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.765
Confidence Interval (2-Sided) 95%
2.100 to 14.882
Estimation Comments The OR of responder rates is estimated and tested between treatment groups using logistic regression model with treatment group, Baseline MG-ADL score and stratification factor (MuSK+ or AChR+). An OR > 1 favours rozanolixizumab.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~10 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is nominal. Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.273
Confidence Interval (2-Sided) 95%
1.653 to 11.791
Estimation Comments The OR of responder rates is estimated and tested between treatment groups using logistic regression model with treatment group, Baseline MG-ADL score and stratification factor (MuSK+ or AChR+). An OR > 1 favours rozanolixizumab.
3.Secondary Outcome
Title Change From Baseline to Day 43 in Myasthenia Gravis-Composite (MG-C) Total Score
Hide Description MG-C scale is a validated assessment and scale tests 10 items with individual item being weighted differently. The items included ptosis/upward gaze (range: 0 [>45 second] - 3 [Immediate]), double vision on lateral gaze (range: 0 [>45 second] - 4 [Immediate]), eye closure (range: 0 [Normal] - 2 [severe weakness]), talking (range: 0 [Normal] - 6 [difficult to understand speech]), chewing (range: 0 [Normal] - 6 [gastric tube]), swallowing (range: 0 [Normal] - 6 [gastric tube]), breathing (range: 0 [Normal] - 9 [ventilator dependence]), neck flexion (range: 0 [Normal] - 4 [severe weakness]), shoulder abduction (range: 0 [Normal] - 5 [severe weakness]) and hip flexion (range: 0 [Normal] - 5 [severe weakness]), lower scores= lower disease activity. Total MG-C score was obtained by summing responses to each individual item and score ranges from 0 to 50, with lower scores indicating lower disease activity. A positive change indicates worsening and a negative change indicates improvement.
Time Frame Baseline and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description:
Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Overall Number of Participants Analyzed 67 66 67
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.029  (0.917) -5.930  (0.916) -7.554  (0.934)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~7 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.901
Confidence Interval (2-Sided) 95%
-6.634 to -1.245
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~10 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.525
Confidence Interval (2-Sided) 95%
-8.303 to -2.968
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
4.Secondary Outcome
Title Change From Baseline to Day 43 in Quantitative Myasthenia Gravis (QMG) Total Score
Hide Description The QMG is a validated assessment and the scale tested 13 items, including ocular and facial involvement, swallowing, speech, limb strength, and forced vital capacity. The total QMG score was obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3) and the score ranges from 0 to 39, with lower scores indicating lower disease activity. A positive change in the score indicates worsening and a negative change indicates improvement.
Time Frame Baseline and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description:
Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Overall Number of Participants Analyzed 67 66 67
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.915  (0.682) -5.398  (0.679) -6.672  (0.692)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~7 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.483
Confidence Interval (2-Sided) 95%
-5.614 to -1.584
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~10 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.756
Confidence Interval (2-Sided) 95%
-6.821 to -2.859
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
5.Secondary Outcome
Title Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Muscle Weakness Fatigability' Score
Hide Description MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose response option that how frequently they experienced muscle weakness fatigability (items 34-42) over the past 7 days using a 5-point Likert scale (1="none of the time" to 5="all of the time") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.
Time Frame Baseline and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description:
Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Overall Number of Participants Analyzed 67 66 67
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-10.588  (3.034) -23.029  (3.034) -25.751  (3.095)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~7 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -12.441
Confidence Interval (2-Sided) 95%
-21.804 to -4.089
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~10 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -15.163
Confidence Interval (2-Sided) 95%
-23.596 to -6.450
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
6.Secondary Outcome
Title Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Physical Fatigue' Score
Hide Description The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose the response option that how frequently they experienced physical fatigue (items 19-33) over the past 7 days using a 5-point Likert scale (1="none of the time" to 5="all of the time") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.
Time Frame Baseline and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description:
Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Overall Number of Participants Analyzed 67 66 67
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-10.637  (3.051) -19.287  (3.046) -25.459  (3.107)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~7 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -8.650
Confidence Interval (2-Sided) 95%
-18.058 to -0.134
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~10 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -14.822
Confidence Interval (2-Sided) 95%
-23.759 to -5.936
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
7.Secondary Outcome
Title Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Bulbar Symptoms' Score
Hide Description The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose response option that best described severity of bulbar muscle weakness (items 6-15) symptoms over past 7 days using a 4-point Likert scale (1="none" to 4="severe") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.
Time Frame Baseline and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
The Randomized Set consisted of all study participants who were randomized and analyzed according to the treatment assigned instead of the actual treatment received.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description:
Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Overall Number of Participants Analyzed 67 66 67
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.519  (2.397) -14.839  (2.406) -14.224  (2.464)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~7 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -11.320
Confidence Interval (2-Sided) 95%
-18.958 to -4.998
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Rozanolixizumab ~10 mg/kg
Comments A sequential testing procedure was used. The parallel gatekeeping testing procedure with a truncated Hochberg test was used to control the familywise type I error rate at a 2-sided alpha level of 0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Confidence intervals and p-values are based on stage-wise inverse normal combination using the Lehmacher and Wassmer method.
Method Lehmacher and Wassmer method
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -10.705
Confidence Interval (2-Sided) 95%
-17.787 to -3.998
Estimation Comments MMRM ANCOVA model included treatment group, Baseline score, region, stratification factor (MuSK+ or AChR+) and treatment group by day (interaction term) as fixed factors and participant as a random effect.
8.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Hide Description A TEAE is defined as an AE starting on or after the time of first administration of investigational medicinal product (IMP) up to and including 8 weeks after the last dose.
Time Frame From Baseline until End of Study Visit (up to Week 14)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all randomized study participants who received at least one dose of IMP and were analyzed according to the actual treatment the participants received. Two participants randomized to RLZ ~7mg/kg, were administered RLZ ~10mg/kg at baseline visit. So, these two participants were included in RLZ ~7 mg/kg group in randomized set, but in RLZ ~10 mg/kg group in safety set.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description:
Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Overall Number of Participants Analyzed 67 64 69
Measure Type: Count of Participants
Unit of Measure: Participants
45
  67.2%
52
  81.3%
57
  82.6%
9.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal of Investigational Medicinal Product (IMP)
Hide Description A TEAE is defined as an AE starting on or after the time of first administration of IMP up to and including 8 weeks after the last dose.
Time Frame From Baseline until End of Study Visit (up to Week 14)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all randomized study participants who received at least one dose of IMP and were analyzed according to the actual treatment the participants received. Two participants randomized to RLZ ~7mg/kg, were administered RLZ ~10mg/kg at baseline visit. So, these two participants were included in RLZ ~7 mg/kg group in randomized set, but in RLZ ~10 mg/kg group in safety set.
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description:
Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
Overall Number of Participants Analyzed 67 64 69
Measure Type: Count of Participants
Unit of Measure: Participants
2
   3.0%
2
   3.1%
4
   5.8%
Time Frame From Baseline until End of Study Visit (up to Week 14)
Adverse Event Reporting Description Safety Set was analyzed for TEAEs. Two participants randomized to RLZ ~7mg/kg, were administered RLZ ~10mg/kg at baseline visit. So, these two participants were included in RLZ ~7 mg/kg group in randomized set, but in RLZ ~10 mg/kg group in safety set.
 
Arm/Group Title Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Hide Arm/Group Description Participants received placebo subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14). Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14). Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 6-week Treatment Period. After 6-week Treatment Period, participants were followed for up to 8 weeks (up to Week 14).
All-Cause Mortality
Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)      0/64 (0.00%)      0/69 (0.00%)    
Hide Serious Adverse Events
Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/67 (8.96%)      5/64 (7.81%)      7/69 (10.14%)    
Gastrointestinal disorders       
Gastritis * 1  0/67 (0.00%)  0 1/64 (1.56%)  1 0/69 (0.00%)  0
Vomiting * 1  0/67 (0.00%)  0 1/64 (1.56%)  1 0/69 (0.00%)  0
General disorders       
Chest pain * 1  0/67 (0.00%)  0 0/64 (0.00%)  0 1/69 (1.45%)  1
Infections and infestations       
COVID-19 pneumonia * 1  1/67 (1.49%)  1 0/64 (0.00%)  0 0/69 (0.00%)  0
Injury, poisoning and procedural complications       
Thoracic vertebral fracture * 1  1/67 (1.49%)  1 0/64 (0.00%)  0 0/69 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  0/67 (0.00%)  0 1/64 (1.56%)  2 0/69 (0.00%)  0
Muscular weakness * 1  1/67 (1.49%)  1 0/64 (0.00%)  0 0/69 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastatic squamous cell carcinoma * 1  0/67 (0.00%)  0 0/64 (0.00%)  0 1/69 (1.45%)  1
Nervous system disorders       
Headache * 1  0/67 (0.00%)  0 0/64 (0.00%)  0 1/69 (1.45%)  1
Myasthenia gravis * 1  1/67 (1.49%)  1 1/64 (1.56%)  1 2/69 (2.90%)  2
Myasthenia gravis crisis * 1  2/67 (2.99%)  2 0/64 (0.00%)  0 0/69 (0.00%)  0
Seizure * 1  0/67 (0.00%)  0 1/64 (1.56%)  1 0/69 (0.00%)  0
Product Issues       
Device dislocation * 1  0/67 (0.00%)  0 0/64 (0.00%)  0 1/69 (1.45%)  1
Renal and urinary disorders       
Nephrolithiasis * 1  0/67 (0.00%)  0 0/64 (0.00%)  0 1/69 (1.45%)  1
Reproductive system and breast disorders       
Cervical dysplasia * 1  0/67 (0.00%)  0 1/64 (1.56%)  1 0/69 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure * 1  0/67 (0.00%)  0 0/64 (0.00%)  0 1/69 (1.45%)  1
1
Term from vocabulary, MedDRA v24.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Rozanolixizumab ~7 mg/kg Rozanolixizumab ~10 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/67 (38.81%)      40/64 (62.50%)      42/69 (60.87%)    
Gastrointestinal disorders       
Diarrhoea * 1  9/67 (13.43%)  14 16/64 (25.00%)  18 11/69 (15.94%)  18
Nausea * 1  5/67 (7.46%)  12 5/64 (7.81%)  7 8/69 (11.59%)  8
Vomiting * 1  1/67 (1.49%)  4 1/64 (1.56%)  3 4/69 (5.80%)  4
General disorders       
Pyrexia * 1  1/67 (1.49%)  1 8/64 (12.50%)  10 14/69 (20.29%)  25
Infections and infestations       
Nasopharyngitis * 1  3/67 (4.48%)  4 1/64 (1.56%)  1 5/69 (7.25%)  5
Urinary tract infection * 1  4/67 (5.97%)  4 2/64 (3.13%)  2 2/69 (2.90%)  2
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  2/67 (2.99%)  2 3/64 (4.69%)  4 5/69 (7.25%)  5
Myalgia * 1  1/67 (1.49%)  1 2/64 (3.13%)  9 4/69 (5.80%)  4
Nervous system disorders       
Headache * 1  13/67 (19.40%)  31 29/64 (45.31%)  54 26/69 (37.68%)  51
Vascular disorders       
Hypertension * 1  0/67 (0.00%)  0 5/64 (7.81%)  5 0/69 (0.00%)  0
1
Term from vocabulary, MedDRA v24.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB
Organization: Cares
Phone: 001 844 599 2273
EMail: UCBCares@ucb.com
Publications of Results:
Bril V, Druzdz A, Grosskreutz J, Habib AA, Mantegazza R, Sacconi S, Utsugisawa K, Vissing J, Vu T, Boehnlein M, Bozorg A, Gayfieva M, Greve B, Woltering F, Kaminski HJ; MG0003 study team. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023 May;22(5):383-394. doi: 10.1016/S1474-4422(23)00077-7. Erratum In: Lancet Neurol. 2023 Oct;22(10):e11.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB Biopharma SRL )
ClinicalTrials.gov Identifier: NCT03971422    
Other Study ID Numbers: MG0003
2019-000968-18 ( EudraCT Number )
First Submitted: May 29, 2019
First Posted: June 3, 2019
Results First Submitted: July 27, 2023
Results First Posted: August 21, 2023
Last Update Posted: September 5, 2023