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

Study Overview
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Brief Summary
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The purpose of the MycarinGstudy is to demonstrate the clinical efficacy and to assess safety and tolerability of rozanolixizumab in patients with generalized myasthenia gravis (MG).

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

Conditions
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Generalized Myasthenia Gravis

Intervention / Treatment
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* Drug: Rozanolixizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study participant must be ≥18 years of age, at the time of signing the informed consent Study participant has documented diagnosis of generalized myasthenia gravis (gMG) at Visit 1, based on study participant's history and supported by previous evaluations Study participant has a confirmed positive record of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) at Screening (Visit 1).The presence of autoantibodies may be confirmed with repeat testing at Visit 1 Study participant has Myasthenia Gravis Foundation of America (MGFA) Class II to IVa at Visit 1 Study participant with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of at least 3 (with ≥3 points from non-ocular symptom) AND a quantitative myasthenia gravis (QMG) score of at least 11 at Visit 1 and at Baseline (Visit 2) Study participant is considered for additional treatment such as intravenous immunoglobulin g (IVIg) or plasma exchange (PEX) by the Investigator Exclusion Criteria: Study participant has a known history of hyperprolinemia Study participant has a clinically relevant active infection (eg, sepsis, pneumonia, or abscess) in the opinion of the Investigator, or had a serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to the first dose of investigational medicinal product (IMP) 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) will be excluded Study participant has experienced hypersensitivity reaction after exposure to other anti-neonatal Fc receptor (FcRn) drugs 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 at Visit 1 or Visit 2 Study participant has a history of a solid organ transplant or hematopoietic stem cell/marrow transplant

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dosage Regimen 1<br>Study participants randomized to dosage regimen 1 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period. | Drug: Rozanolixizumab<br>* Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.<br>* Other names: UCB7665;|
| Experimental: Dosage Regimen 2<br>Study participants randomized to dosage regimen 2 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period. | Drug: Rozanolixizumab<br>* Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.<br>* Other names: UCB7665;|
| Placebo Comparator: Placebo<br>Study participants randomized to this arm will receive placebo. | Other: Placebo<br>* Subjects will receive placebo at pre-specified time points.<br>* Other names: PBO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Day 43 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | 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. | Baseline and Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Myasthenia Gravis-Activities of Daily Living (MG-ADL) Response at Day 43 | 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. | Day 43 | 
| Change From Baseline to Day 43 in Myasthenia Gravis-Composite (MG-C) Total Score | 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. | Baseline and Day 43 | 
| Change From Baseline to Day 43 in Quantitative Myasthenia Gravis (QMG) Total Score | 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. | Baseline and Day 43 | 
| Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Muscle Weakness Fatigability' Score | 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. | Baseline and Day 43 | 
| Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Physical Fatigue' Score | 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. | Baseline and Day 43 | 
| Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Bulbar Symptoms' Score | 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. | Baseline and Day 43 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. | From Baseline until End of Study Visit (up to Week 14) | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal of Investigational Medicinal Product (IMP) | 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. | From Baseline until End of Study Visit (up to Week 14) | 

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