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

Phase 3

Completed

• Conditions: Generalized Myasthenia Gravis
• Interventions: Other: Placebo; Drug: Rozanolixizumab

• Registration Number: NCT03971422
• Lead Sponsor: UCB Biopharma SRL

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-29
• Study First Submitted QC: 2019-05-29
• Study Start: 2019-06-03
• Study First Posted: 2019-06-03
• Primary Completion: 2021-08-31
• Study Completion: 2021-10-26
• Disposition First Submitted: 2022-08-30
• Disposition First Submitted QC: 2022-08-30
• Disposition First Posted: 2022-08-31
• Results First Submitted: 2023-07-27
• Results First Submitted QC: 2023-07-27
• Results First Posted: 2023-08-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-08
• Last Update Posted: 2024-10-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Study participants randomized to this arm will receive placebo.
Dosage Regimen 1	Rozanolixizumab	Study participants randomized to dosage regimen 1 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period.
Dosage Regimen 2	Rozanolixizumab	Study participants randomized to dosage regimen 2 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Day 43 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score	Baseline and Day 43	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.

Secondary Outcome Measures

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

Trial Locations

Locations (112)

Mg0003 50092; 🇺🇸 Orange, California, United States

Mg0003 50105; 🇺🇸 Saint Louis, Missouri, United States

Mg0003 40149; 🇮🇹 Lazio, Italy

Mg0003 40130; 🇫🇷 Marseille, France

Mg0003 50109; 🇺🇸 Chicago, Illinois, United States

Mg0003 50075; 🇺🇸 Augusta, Georgia, United States

Mg0003 50073; 🇺🇸 Tampa, Florida, United States

Mg0003 50110; 🇺🇸 Ann Arbor, Michigan, United States

Mg0003 50117; 🇺🇸 Charlotte, North Carolina, United States

Mg0003 40135; 🇩🇪 Gummersbach, Germany

Mg0003 50121; 🇺🇸 Lexington, Kentucky, United States

Mg0003 20160; 🇬🇪 Tbilisi, Georgia

Mg0003 40510; 🇫🇷 Le Kremlin-Bicêtre, France

Mg0003 40017; 🇫🇷 Nantes, France

Mg0003 40160; 🇪🇸 Barcelona, Spain

Mg0003 40350; 🇪🇸 Murcia, Spain

Mg0003 20068; 🇯🇵 Chiba-Shi, Japan

Mg0003 20079; 🇯🇵 Hiroshima, Japan

Mg0003 40078; 🇩🇪 Leipzig, Germany

Mg0003 40267; 🇪🇸 Barcelona, Spain

Mg0003 40307; 🇮🇹 Napoli, Italy

Mg0003 40129; 🇫🇷 Bordeaux, France

Mg0003 40426; 🇫🇷 Lyon, France

Mg0003 40070; 🇫🇷 Clermont-Ferrand, France

Mg0003 40168; 🇬🇧 Nottingham, United Kingdom

Mg0003 40512; 🇫🇷 Garches, France

Mg0003 40360; 🇫🇷 Limoges, France

Mg0003 40131; 🇫🇷 Strasbourg, France

Mg0003 40175; 🇬🇧 London, United Kingdom

Mg0003 40162; 🇪🇸 Madrid, Spain

Mg0003 40134; 🇩🇪 Essen, Germany

Mg0003 40139; 🇩🇪 Jena, Germany

Mg0003 40177; 🇩🇪 Münster, Germany

Mg0003 40082; 🇭🇺 Kistarcsa, Hungary

Mg0003 40283; 🇮🇹 Bologna, Italy

Mg0003 40144; 🇮🇹 Milano, Italy

Mg0003 40157; 🇪🇸 Hospitalet de Llobregat, Spain

Mg0003 40140; 🇩🇪 Göttingen, Germany

Mg0003 40161; 🇪🇸 Madrid, Spain

Mg0003 20070; 🇯🇵 Shinjuku-Ku, Japan

Mg0003 40159; 🇪🇸 Barcelona, Spain

Mg0003 40341; 🇪🇸 Málaga, Spain

Mg0003 50096; 🇺🇸 Philadelphia, Pennsylvania, United States

Mg0003 50072; 🇺🇸 Los Angeles, California, United States

Mg0003 50101; 🇺🇸 Aurora, Colorado, United States

Mg0003 50102; 🇺🇸 Detroit, Michigan, United States

Mg0003 50104; 🇺🇸 Rochester, Minnesota, United States

Mg0003 50077; 🇺🇸 New York, New York, United States

Mg0003 50086; 🇺🇸 Charlotte, North Carolina, United States

Mg0003 50090; 🇺🇸 Winston-Salem, North Carolina, United States

Mg0003 50076; 🇺🇸 Columbus, Ohio, United States

Mg0003 50089; 🇺🇸 Philadelphia, Pennsylvania, United States

Mg0003 50084; 🇺🇸 Charleston, South Carolina, United States

Mg0003 50067; 🇨🇦 Calgary, Canada

Mg0003 50066; 🇨🇦 Montréal, Canada

Mg0003 50070; 🇨🇦 Québec, Canada

Mg0003 50069; 🇨🇦 Toronto, Canada

Mg0003 40125; 🇨🇿 Ostrava, Czechia

Mg0003 40124; 🇨🇿 Praha 2, Czechia

Mg0003 50323; 🇺🇸 Honolulu, Hawaii, United States

Mg0003 50074; 🇺🇸 Fairway, Kansas, United States

Mg0003 50097; 🇺🇸 San Francisco, California, United States

Mg0003 50099; 🇺🇸 San Francisco, California, United States

Mg0003 50122; 🇺🇸 Miami, Florida, United States

Mg0003 50120; 🇺🇸 Miami, Florida, United States

Mg0003 50114; 🇺🇸 Indianapolis, Indiana, United States

Mg0003 50113; 🇺🇸 Houston, Texas, United States

Mg0003 40128; 🇩🇰 Aalborg, Denmark

Mg0003 40127; 🇩🇰 Aarhus n, Denmark

Mg0003 40489; 🇩🇰 Odense, Denmark

Mg0003 40126; 🇩🇰 Copenhagen, Denmark

Mg0003 50082; 🇺🇸 Scottsdale, Arizona, United States

Mg0003 40121; 🇧🇪 Bruxelles, Belgium

Mg0003 20035; 🇯🇵 Bunkyō-Ku, Japan

Mg0003 40153; 🇵🇱 Poznań, Poland

Mg0003 20067; 🇯🇵 Sapporo, Japan

Mg0003 20076; 🇯🇵 Shinjuku-Ku, Japan

Mg0003 20169; 🇷🇺 Novosibirsk, Russian Federation

Mg0003 40468; 🇷🇸 Belgrade, Serbia

Mg0003 40467; 🇷🇸 Niš, Serbia

Mg0003 20086; 🇨🇳 Taipei, Taiwan

Mg0003 20081; 🇨🇳 Taipei, Taiwan

Mg0003 50088; 🇺🇸 Washington, District of Columbia, United States

Mg0003 20165; 🇬🇪 Tbilisi, Georgia

Mg0003 20071; 🇯🇵 Nagasaki, Japan

Mg0003 20077; 🇯🇵 Sendai, Japan

Mg0003 20028; 🇷🇺 Saint Petersburg, Russian Federation

Mg0003 50081; 🇺🇸 Phoenix, Arizona, United States

Mg0003 20161; 🇬🇪 Tbilisi, Georgia

Mg0003 20163; 🇬🇪 Tbilisi, Georgia

Mg0003 20078; 🇯🇵 Hanamaki-Shi, Japan

Mg0003 20074; 🇯🇵 Ōsaka-sayama, Japan

Mg0003 40155; 🇵🇱 Gdańsk, Poland

Mg0003 40151; 🇵🇱 Lublin, Poland

Mg0003 40154; 🇵🇱 Łódź, Poland

Mg0003 40178; 🇭🇺 Nyiregyhaza, Hungary

Mg0003 20075; 🇯🇵 Kobe, Japan

Mg0003 20032; 🇯🇵 Suita, Japan

Mg0003 20029; 🇷🇺 Saint Petersburg, Russian Federation

Mg0003 20027; 🇷🇺 Moscow, Russian Federation

Mg0003 20168; 🇷🇺 Krasnoyarsk, Russian Federation

Mg0003 20001; 🇷🇺 Saint Petersburg, Russian Federation

Mg0003 20055; 🇷🇺 Saint Petersburg, Russian Federation

Mg0003 20080; 🇨🇳 Taichung, Taiwan

Mg0003 20082; 🇨🇳 Taoyuan, Taiwan

Mg0003 20197; 🇷🇺 Samara, Russian Federation

Mg0003 40132; 🇫🇷 Nice Cedex 1, France

Mg0003 40146; 🇮🇹 Pavia, Italy

Mg0003 40148; 🇮🇹 Roma, Italy

Mg0003 40150; 🇮🇹 Roma, Italy

Mg0003 40308; 🇪🇸 San Sebastián De Los Reyes, Spain

Mg0003 40133; 🇫🇷 Paris, France