A Study to Evaluate Rozanolixizumab in Study Participants With Generalized Myasthenia Gravis

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and efficacy of additional 6-week treatment cycles with rozanolixizumab in study participants with generalized myasthenia gravis (gMG).

Official Title
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An Open-Label Extension Study to Evaluate Rozanolixizumab in Study Participants With Generalized Myasthenia Gravis

Conditions
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Generalized Myasthenia Gravis

Intervention / Treatment
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* Drug: Rozanolixizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study participant must meet one of the following: completed MG0003 [NCT03971422] required rescue therapy during the Observation Period in MG0003 or completed at least 6 visits in MG0004 [NCT04124965] Body weight ≥35 kg at Baseline (Day 1) Study participants may be male or female Exclusion Criteria: Study participant has a known hypersensitivity to any components of the study medication or other anti-neonatal Fc receptor (FcRn) medications Study participant with a known tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent tuberculosis infection (LTBI), or current/history of nontuberculous mycobacterial infection (NTMBI) Study participant met any mandatory withdrawal or mandatory study drug discontinuation criteria in MG0003, or MG0004, or permanently discontinued study drug in either study Study participant intends to have a live vaccination during the course of the study or within 8 weeks following the final dose of rozanolixizumab Study participant with severe (defined as Grade 3 on the Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale) weakness affecting oropharyngeal or respiratory muscles, or who has myasthenic crisis or impending crisis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rozanolixizumab dosage regimen 1<br>Study participants randomized/assigned to dosage regimen 1 will receive assigned dosage of rozanolixizumab for the initial cycle. The dose regimen may be switched before the start of each subsequent treatment cycle based on investigator discretion. | Drug: Rozanolixizumab<br>* Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.<br>* Other names: UCB7665;|
| Experimental: Rozanolixizumab dosage regimen 2<br>Study participants randomized/assigned to dosage regimen 2 will receive assigned dosage of rozanolixizumab for the initial cycle. The dose regimen may be switched before the start of each subsequent treatment cycle based on investigator discretion. | Drug: Rozanolixizumab<br>* Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.<br>* Other names: UCB7665;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with treatment-emergent adverse events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline (Day 1) to End of Study (average of 20 months) | 
| Percentage of participants with TEAEs leading to withdrawal of investigational medicinal product (IMP) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs leading to permanent withdrawal of study medication. | From Baseline (Day 1) to End of Study (average of 20 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline (Day 1) to Day 43 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score within one treatment cycle | The Outcome Measure is applicable for the first 3 treatment cycles. The total MG-ADL score is obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3). The score ranges from 0 to 24, with a higher score indicating more disability. A positive change indicates worsening and a negative change indicates improvement. | From Baseline (Day 1) to end of treatment cycle (up to 6 weeks) | 
| Change from Baseline (Day 1) to Day 43 in Quantitative Myasthenia Gravis (QMG) score within one treatment cycle | The Outcome Measure is applicable for the first 3 treatment cycles. The total QMG score is obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity. | From Baseline (Day 1) to end of treatment cycle (up to 6 weeks) | 
| Change from Baseline (Day 1) to Day 43 in Myasthenia Gravis-Composite (MG-C) score within one treatment cycle | The Outcome Measure is applicable for the first 3 treatment cycles. The total MG-C score is obtained by summing the responses to each individual item (10 items; Grade:0-9 depending on item). The score ranges from 0 to 50, with lower scores indicating lower disease activity. | From Baseline (Day 1) to end of treatment cycle (up to 6 weeks) | 
| Change from Baseline (Day 1) to Day 43 in Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Muscle Weakness Fatigability' score within one treatment cycle | The Outcome Measure is applicable for the first 3 treatment cycles. The MG symptoms PRO instrument consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). The study participant will be asked to choose the response option that best describes the severity of ocular, bulbar, and respiratory symptoms over the past 7 days using a 4-point Likert scale (none to severe) and how frequently they experience physical fatigue and muscle weakness fatigability over the past 7 days using a 5-point Likert scale (none of the time to all of the time), respectively. | From Baseline (Day 1) to end of treatment cycle (up to 6 weeks) | 
| Change from Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Physical Fatigue' score within one treatment cycle | The Outcome Measure is applicable for the first 3 treatment cycles. The MG symptoms PRO instrument consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). The study participant will be asked to choose the response option that best describes the severity of ocular, bulbar, and respiratory symptoms over the past 7 days using a 4-point Likert scale (none to severe) and how frequently they experience physical fatigue and muscle weakness fatigability over the past 7 days using a 5-point Likert scale (none of the time to all of the time), respectively. | From Baseline (Day 1) to end of treatment cycle (up to 6 weeks) | 
| Change from Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Bulbar symptoms' score within one treatment cycle | The Outcome Measure is applicable for the first 3 treatment cycles. The MG symptoms PRO instrument consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). The study participant will be asked to choose the response option that best describes the severity of ocular, bulbar, and respiratory symptoms over the past 7 days using a 4-point Likert scale (none to severe) and how frequently they experience physical fatigue and muscle weakness fatigability over the past 7 days using a 5-point Likert scale (none of the time to all of the time), respectively. | From Baseline (Day 1) to end of treatment cycle (up to 6 weeks) | 
| MG-ADL responder (≥2.0-point improvement from Baseline [Day 1] to end of Day 43) within one treatment cycle | The Outcome Measure is applicable for the first 3 treatment cycles. A MG-ADL responder is defined as achieving at least 2.0-point improvement in the MG-ADL score from Baseline. | From Baseline (Day 1) to end of treatment cycle (up to 6 weeks) | 
| Time to MG-ADL response (≥2.0-point improvement from Baseline [Day 1]) within one treatment cycle | The Outcome Measure is applicable for the first 3 treatment cycles. Time to achieve MG-ADL response, defined as at least 2.0-point improvement from Baseline. | From Baseline (Day 1) to end of treatment cycle (up to 6 weeks) | 
| Time between consecutive treatment cycles | Time between consecutive treatment cycles: Study participants will be assessed for MG worsening prior to repeated cycles. In case of symptom worsening (eg, an increase of 2.0 points on the MG-ADL or 3.0 points on the QMG scale) between assessments, resulting in a need for additional treatment, study participants will undergo another 6-week treatment cycle followed by an Observation Period, based on the Investigator's discretion. | From end of the 6-week treatment cycle (Day 43) to the next 6-week treatment cycle (Day 1), assessed up to 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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UCB7665, generalized myasthenia gravis, rozanolixizumab, gMG