A Study to Evaluate Rozanolixizumab in Study Participants With Generalized Myasthenia Gravis
- Registration Number
- NCT04650854
- Lead Sponsor
- UCB Biopharma SRL
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 165
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rozanolixizumab dosage regimen 1 Rozanolixizumab 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. Rozanolixizumab dosage regimen 2 Rozanolixizumab 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline (Day 1) to End of Study (up to 34 months) An adverse event (AE) was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which did not necessarily had 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. TEAE was defined as any event that was not present prior to first dose of investigational medicinal product (IMP), or any unresolved event already present that worsened in intensity following treatment, up to 8 weeks after end of Treatment Period or after last dose of IMP in participants who discontinued study or IMP.
Percentage of Participants With TEAEs Leading to Withdrawal of Investigational Medicinal Product (IMP) From Baseline (Day 1) to End of Study (up to 34 months) An adverse event (AE) was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs leading to permanent withdrawal of study medication.
- Secondary Outcome Measures
Name Time Method Change From Baseline (Day 1) to Day 43 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score Within One Treatment Cycle (Cycle 1, 2, and 3) From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3) The MG-ADL is an 8-item PRO instrument developed on basis of QMG. The MG-ADL targeted symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The total MG-ADL score was obtained by summing responses to each individual item (8 items; Grades: 0, 1, 2, 3), where 0= no symptoms or impaired performance and 3= most severe symptoms or impaired performance. The total score ranges from 0 to 24, with higher score indicating more disability. A positive change in score indicates worsening and negative change indicates improvement. For analyses done by study cycle, Baseline values were last available values prior to or on the same date of first administration of IMP at each cycle (Baseline \[Day 1\]) value for that cycle.
Change From Baseline (Day 1) to Day 43 in Quantitative Myasthenia Gravis (QMG) Score Within One Treatment Cycle (Cycle 1, 2, and 3) From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3) 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. For the analyses done by study cycle, Baseline values were the last available values prior to or on the same date (and same time if time was collected for the individual assessment) of first administration of IMP at each cycle (ie, Baseline \[Day 1\]) value for that cycle.
Change From Baseline (Day 1) to Day 43 in Myasthenia Gravis-Composite (MG-C) Score Within One Treatment Cycle (Cycle 1, 2, and 3) From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3) MG-C scale consists of 10 items which included ptosis (score range=0 to 3), double vision on lateral gaze left/right/both (score range=0 to 4), eye closure (score range=0 to 2), talking (score range=0 to 6), chewing (score range=0 to 6), swallowing (score range=0 to 6), breathing (score range=0 to 9), neck flexion or extension (score range=0 to 4), shoulder abduction (score range=0 to 5) and hip flexion (score range= 0 to 5), lower scores= lower disease activity. Total MG-C score obtained by summing responses to each individual item and score ranges from 0 - 50, (lower scores indicating lower disease activity). Positive change = worsening, and negative change = improvement. For analyses done by study cycle, Baseline values were last available values prior to or on the same date of first administration of IMP at each cycle (Baseline \[Day 1\]) value for that cycle.
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 (Cycle 1, 2, and 3) From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3) The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular symptoms (1-5); bulbar muscle weakness (6-15); respiratory muscle weakness (16-18); physical fatigue (19-33) and muscle weakness fatigability (34-42). Study participants had to choose response option that best described severity of ocular, bulbar, and respiratory symptoms over past 7 days using a 4-point Likert scale ("none" to "severe") and frequency of experiencing physical fatigue and muscle weakness fatigability over past 7 days using a 5-point Likert scale (1="none of the time" - 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, higher scores indicates more severe symptoms. For analyses done by study cycle, Baseline values were last available values prior to or on the same date of first administration of IMP at each cycle (Baseline \[Day 1\]) value for that cycle.
Change From Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Physical Fatigue' Score Within One Treatment Cycle (Cycle 1, 2, and 3) From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3) The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (1-5); bulbar muscle weakness (6-15); respiratory muscle weakness (16-18); physical fatigue (19-33) and muscle weakness fatigability (34-42). Study participants had to choose response option based on frequency of experiencing physical fatigue (19-33) over past 7 days using a 5-point Likert scale (1="none of time" - 5="all of time") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100, higher scores indicated severe symptoms.
Change From Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Bulbar Muscle Weakness' Score Within One Treatment Cycle (Cycle 1, 2, and 3) From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3) The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (1-5); bulbar muscle weakness (6-15); respiratory muscle weakness (16-18); physical fatigue (19-33) and muscle weakness fatigability (34-42). Bulbar symptoms are now recognised as bulbar muscle weakness. Study participants were asked to choose response option that best described severity of bulbar muscle weakness (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, higher scores indicated severe symptoms.
MG-ADL Responder Rate (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3 [Day 43]) Day 43 of Cycle 1, 2, and 3 The MG-ADL is an 8-item 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 MG-ADL responder was defined as achieving at least 2.0-point improvement (decrease) in the MG-ADL score from Baseline.
Time to MG-ADL Response (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3) From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3) Time to achieve MG-ADL response, defined as at least 2.0-point improvement from Baseline. Time to first MG-ADL response (in days) by study cycle was defined as date of first MG-ADL Response within study cycle - date of MG-ADL Baseline within study cycle + 1.
Time Between Consecutive Treatment Cycles 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 Time between consecutive treatment cycles: Study participants were assessed for MG worsening prior to repeated cycles. In case of symptom worsening (eg, an increase of 2.0 points on MG-ADL or 3.0 points on QMG scale) between assessments, resulted additional treatment, study participants undergone another 6-week treatment cycle followed by an Observation Period, based on Investigator's discretion. Time between treatment cycles was calculated as: date of first sc infusion in consecutive cycle - date of last sc infusion before new cycle + 1 (or date of censoring - date of last sc infusion before potential new cycle + 1).
Trial Locations
- Locations (69)
Mg0007 20086
🇨🇳Taipei City, Taiwan
Mg0007 50073
🇺🇸Tampa, Florida, United States
Mg0007 50122
🇺🇸Miami, Florida, United States
Mg0007 50092
🇺🇸Orange, California, United States
Mg0007 50077
🇺🇸New York, New York, United States
Mg0007 50323
🇺🇸Honolulu, Hawaii, United States
Mg0007 50070
🇨🇦Quebec, Canada
Mg0007 50113
🇺🇸Houston, Texas, United States
Mg0007 40127
🇩🇰Aarhus, Denmark
Mg0007 50124
🇨🇦Montreal, Canada
Mg0007 40128
🇩🇰Aalborg, Denmark
Mg0007 40132
🇫🇷Nice Cedex 1, France
Mg0007 40360
🇫🇷Limoges, France
Mg0007 40139
🇩🇪Jena, Germany
Mg0007 40177
🇩🇪Münster, Germany
Mg0007 40144
🇮🇹Milano, Italy
Mg0007 40134
🇩🇪Essen, Germany
Mg0007 40140
🇩🇪Göttingen, Germany
Mg0007 40126
🇩🇰Copenhagen, Denmark
Mg0007 20078
🇯🇵Hanamaki-shi, Japan
Mg0007 20075
🇯🇵Kobe, Japan
Mg0007 20071
🇯🇵Nagasaki-shi, Japan
Mg0007 20169
🇷🇺Novosibirsk, Russian Federation
Mg0007 20077
🇯🇵Sendai, Japan
Mg0007 40155
🇵🇱Gdansk, Poland
Mg0007 40154
🇵🇱Lodz, Poland
Mg0007 40467
🇷🇸NIS, Serbia
Mg0007 20055
🇷🇺Saint-petersburg, Russian Federation
Mg0007 40160
🇪🇸Barcelona, Spain
Mg0007 20028
🇷🇺Saint-petersburg, Russian Federation
Mg0007 40350
🇪🇸Murcia, Spain
Mg0007 40146
🇮🇹Pavia, Italy
Mg0007 40148
🇮🇹Roma, Italy
Mg0007 40150
🇮🇹Roma, Italy
Mg0007 20070
🇯🇵Shinjuku-ku, Japan
Mg0007 20035
🇯🇵Bunkyo-ku, Japan
Mg0007 20068
🇯🇵Chiba-shi, Japan
Mg0007 50099
🇺🇸San Francisco, California, United States
Mg0007 50120
🇺🇸Miami, Florida, United States
Mg0007 50114
🇺🇸Indianapolis, Indiana, United States
Mg0007 50121
🇺🇸Lexington, Kentucky, United States
Mg0007 50075
🇺🇸Augusta, Georgia, United States
Mg0007 50096
🇺🇸Philadelphia, Pennsylvania, United States
Mg0007 50090
🇺🇸Winston-Salem, North Carolina, United States
Mg0007 50071
🇨🇦Edmonton, Canada
Mg0007 50066
🇨🇦Montreal, Canada
Mg0007 40124
🇨🇿Praha 2, Czechia
Mg0007 50069
🇨🇦Toronto, Canada
Mg0007 40125
🇨🇿Ostrava - Poruba, Czechia
Mg0007 40129
🇫🇷Bordeaux, France
Mg0007 20160
🇬🇪Tbilisi, Georgia
Mg0007 20161
🇬🇪Tbilisi, Georgia
Mg0007 40131
🇫🇷Strasbourg, France
Mg0007 40133
🇫🇷Paris, France
Mg0007 20163
🇬🇪Tbilisi, Georgia
Mg0007 20164
🇬🇪Tbilisi, Georgia
Mg0007 20165
🇬🇪Tbilisi, Georgia
Mg0007 40283
🇮🇹Bologna, Italy
Mg0007 40307
🇮🇹Napoli, Italy
Mg0007 40078
🇩🇪Leipzig, Germany
Mg0007 20032
🇯🇵Suita, Japan
Mg0007 20076
🇯🇵Shinjuku-ku, Japan
Mg0007 40151
🇵🇱Lublin, Poland
Mg0007 40153
🇵🇱Poznan, Poland
Mg0007 20001
🇷🇺Saint-petersburg, Russian Federation
Mg0007 40157
🇪🇸Hospitalet de Llobregat, Spain
Mg0007 20081
🇨🇳Taipei City, Taiwan
Mg0007 40308
🇪🇸San Sebastián de Los Reyes, Spain
Mg0007 20079
🇯🇵Hiroshima, Japan