Clinical Trial Results:
A Randomized, Open-Label Extension Study to Investigate the Long-Term Safety, Tolerability, and Efficacy of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis
Summary
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EudraCT number |
2019-000969-21 |
Trial protocol |
HU GB DK BE DE ES CZ PL IT |
Global end of trial date |
01 Sep 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Sep 2022
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First version publication date |
14 Sep 2022
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MG0004
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04124965 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
UCB Biopharma SRL
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Sponsor organisation address |
Allée de la Recherche 60, Brussels, Belgium, 1070
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Public contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Scientific contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Oct 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Sep 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Sep 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluate the long-term safety and tolerability of rozanolixizumab in study participants with generalized myasthenia gravis (MG)
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Protection of trial subjects |
During the conduct of the study all participants were closely monitored.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
29 Oct 2019
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
2 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 10
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Country: Number of subjects enrolled |
Czechia: 2
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Country: Number of subjects enrolled |
Denmark: 1
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Country: Number of subjects enrolled |
France: 12
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Country: Number of subjects enrolled |
Germany: 3
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Japan: 6
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Country: Number of subjects enrolled |
Poland: 7
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Country: Number of subjects enrolled |
Russian Federation: 6
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Country: Number of subjects enrolled |
Spain: 3
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Country: Number of subjects enrolled |
Taiwan: 2
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Country: Number of subjects enrolled |
United States: 17
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Worldwide total number of subjects |
71
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EEA total number of subjects |
30
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
55
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From 65 to 84 years |
14
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85 years and over |
2
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Recruitment
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Recruitment details |
The study started to enroll study participants in Oct 2019 and concluded in Sep 2021. | ||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Participant Flow refers to the Randomized Set which consisted of all study participants who were randomized, using the treatment assigned instead of the actual treatment received. | ||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Rozanolixizumab ~7 mg/kg | ||||||||||||||||||||||||||||||||||||
Arm description |
Participants received rozanolixizumab equivalent to approximately 7 milligrams/kilogram (mg/kg), subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Rozanolixizumab
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Investigational medicinal product code |
UCB7665
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received rozanolixizumab equivalent to 7 mg/kg subcutaneously on a weekly basis over a 52-week Treatment Period.
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Arm title
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Rozanolixizumab ~10 mg/kg | ||||||||||||||||||||||||||||||||||||
Arm description |
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Rozanolixizumab
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Investigational medicinal product code |
UCB7665
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received rozanolixizumab equivalent to 10 mg/kg subcutaneously on a weekly basis over a 52-week Treatment Period.
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Baseline characteristics reporting groups
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Reporting group title |
Rozanolixizumab ~7 mg/kg
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Reporting group description |
Participants received rozanolixizumab equivalent to approximately 7 milligrams/kilogram (mg/kg), subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rozanolixizumab ~10 mg/kg
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Reporting group description |
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Rozanolixizumab ~7 mg/kg
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Reporting group description |
Participants received rozanolixizumab equivalent to approximately 7 milligrams/kilogram (mg/kg), subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). | ||
Reporting group title |
Rozanolixizumab ~10 mg/kg
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Reporting group description |
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). | ||
Subject analysis set title |
Rozanolixizumab ~7 mg/kg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). This set included participants that switched to Rozanolixizumab equivalent to approximately 10 mg/kg at least once during the study.
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Subject analysis set title |
Rozanolixizumab ~10 mg/kg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). This set included participants that switched to Rozanolixizumab equivalent to approximately 7 mg/kg at least once during the study.
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End point title |
Percentage of participants with treatment-emergent adverse events (TEAEs) [1] | ||||||||||||
End point description |
A TEAE is defined as an AE starting on or after the time of first administration of investigational medicinal product (IMP) or any unresolved event already present before the first administration of IMP that worsened in intensity following exposure to IMP, up to 8 weeks after the last dose of IMP in study participants who discontinued the study or IMP. The Safety Set (SS) consisted of all randomized study participants who received at least 1 dose of IMP in this study. This endpoint was planned to be analyzed using the SS by most recent dose received i.e. the most recent dose received at or before the AE onset. Participants who switched doses were counted in both rozanolixizumab (RLZ) doses.
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End point type |
Primary
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End point timeframe |
From Baseline until End of Study (up to Week 60)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only. |
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No statistical analyses for this end point |
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End point title |
Percentage of participants with treatment-emergent adverse events (TEAEs) leading to permanent withdrawal of study medication [2] | ||||||||||||
End point description |
A TEAE is defined as an AE starting on or after the time of first administration of IMP or any unresolved event already present before the first administration of IMP that worsened in intensity following exposure to IMP, up to 8 weeks after the last dose of IMP in study participants who discontinued the study or IMP. The Safety Set consisted of all randomized study participants who received at least 1 dose of IMP in this study. This endpoint was planned to be analyzed using the SS by most recent dose received i.e. the most recent dose received at or before the AE onset. Participants who switched doses were counted in both rozanolixizumab doses.
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End point type |
Primary
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End point timeframe |
From Baseline until End of Study (up to Week 60)
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score at each scheduled assessment during Treatment and Observation Periods | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
MG-ADL is an 8-item patient-reported outcome (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 indicates worsening and a negative change indicates improvement. The Safety Set consisted of all randomized study participants who received at least 1 dose of IMP in this study. Here, number analyzed (n) signifies those who were evaluable at specified time points. 99999 signifies that as pre-specified in the Statistical Analysis Plan, Standard Deviation was only calculated if there were a minimum of 4 participants.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 52 and 60
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Myasthenia Gravis-Composite (MG-C) total score at each scheduled assessment during Treatment and Observation Periods | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
MG-C scale is a validated assessment and scale tests 10 items with individual items being weighted differently. Items: ptosis/upward gaze (range: 0 [>45 second] -3 [Immediate]), double vision on lateral gaze (0 [>45 second] -4 [Immediate]), eye closure (0 [Normal] -2 [severe weakness]), talking (0 [Normal] -6 [difficult to understand speech]), chewing & swallowing (0 [Normal] -6 [gastric tube]), breathing (0 [Normal] -9 [ventilator dependence]), neck flexion (0 [Normal] -4 [severe weakness]), shoulder abduction & hip felxion (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,lower scores=lower disease activity.A positive change=worsening and a negative change=improvement.Analysis population was SS.n= participants evaluable at specified time points.99999=mean and S.D. was calculated if there were a minimum of 3 participants and 4 participants respectively.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 52 and 60
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Quantitative Myasthenia Gravis (QMG) total score at each scheduled assessment during Treatment and Observation Periods | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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 indicates worsening and a negative change indicates improvement. The Safety Set consisted of all randomized study participants who received at least 1 dose of IMP in this study. Here, number analyzed signifies those participants who were evaluable at specified time points. 99999 signifies that as pre-specified in the Statistical Analysis Plan, mean was only calculated if there were a minimum of 3 participants and standard deviation was only calculated if there were a minimum of 4 participants.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 52 and 60
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No statistical analyses for this end point |
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End point title |
Percentage of participants using rescue medication (intravenous infusion of immunoglobulin G (IVIg) or plasma exchange (PEX)) | ||||||||||||
End point description |
Rescue therapy consisted of IVIg or PEX. Study participants who experienced disease worsening (eg, an increase of 2 points on the MG-ADL or 3 points on the QMG scale between 2 consecutive visits) may be considered for rescue therapy at the discretion of the Investigator. The Safety Set consisted of all randomized study participants who received at least 1 dose of IMP in this study.
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End point type |
Secondary
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End point timeframe |
From Baseline until End of Study (up to Week 60)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From Baseline until End of Study (up to Week 60)
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Adverse event reporting additional description |
TEAEs are reported in the safety section. TEAEs were planned to be analyzed using SS by most recent dose received i.e. the most recent dose received at or before the AE onset. Participants who switched doses were counted in both RLZ doses.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Rozanolixizumab ~10 mg/kg
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Reporting group description |
Participants received rozanolixizumab equivalent to approximately 10 mg/kg, subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). This set included participants that switched to Rozanolixizumab equivalent to approximately 7 mg/kg at least once during the study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rozanolixizumab ~7 mg/kg
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Reporting group description |
Participants received rozanolixizumab equivalent to approximately 7 mg/kg, subcutaneously on a weekly basis over a 52-week Treatment Period. After 52-week Treatment Period, participants were followed up for 8 weeks (up to Week 60). This set included participants that switched to Rozanolixizumab equivalent to approximately 10 mg/kg at least once during the study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Nov 2019 |
Protocol Amendment 1 (dated 01 Nov 2019) was a substantial amendment implemented to reference to another lead-in study, MGC003, throughout the protocol; however, MGC003 was not conducted. Other changes included additional wording to allow study participants to enroll into a substudy at selected sites (however, no study participants were included in the substudy), addition of 2 exploratory objective and endpoints (1 to assess the effect of rozanolixizumab on tetanus IgG antibodies, and 1 to capture the reduction steroid use in study participants receiving rozanolixizumab) and changes throughout the Schedule of Assessments. |
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30 Jul 2020 |
Protocol Amendment 2 (dated 30 Jul 2020) was a substantial amendment implemented to introduce the transition of study participants to MG0007 and closure of MG0004, once MG0007 was available as the open-label study to MG0003. Other changes included updates to decrease the complexity of assessments to be performed; to clarify some operational aspects of the study; to incorporate the harmonization of inclusion criteria with studies performed across the rozanolixizumab clinical development program; and to include the management of study participant treatment during the coronavirus disease 2019 (COVID-19) pandemic including
contingency measures. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |