Generalized Myasthenia Gravis
Conditions
Keywords
UCB7665, generalized myasthenia gravis, rozanolixizumab, gMG
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).
Interventions
DRUGRozanolixizumab
Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Study participant must meet one of the following: 1. completed MG0003 \[NCT03971422\] 2. required rescue therapy during the Observation Period in MG0003 or 3. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
Canada, Czechia, Denmark, France, Georgia, Germany, Italy, Japan, Poland, Russia, Serbia, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORUCB Cares
001 844 599 22733 (UCB)
Participant flow
Recruitment details
The study started to enroll participants in February 2021 and concluded in January 2024. Participant Flow refers to Full Analysis Set (FAS).
Pre-assignment details
Participants who completed MG0003 (NCT03971422) or required rescue therapy during Observation Period (OP) in MG0003 (except for participants who received intravenous immunoglobulin/plasma exchange in MG0003) or completed at least 6 treatment visits in MG0004 (NCT04124965) were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Enrolled, But Not Treated Participants were enrolled but did not receive a treatment cycle of Rozanolixizumab (RLZ) in MG0007 per the Investigator's discretion. | 8 |
| Rozanolixizumab ~7 mg/kg Eligible participants from MG0003 were randomized to receive an initial fixed 6-week treatment cycle of subcutaneous (sc) dose of Rozanolixizumab (RLZ) equivalent to approximately 7 milligrams/kilogram (mg/kg) once weekly (QW), followed by OP that began after last dose of that treatment cycle. Eligible participants from MG0004 who completed at least 6 scheduled visits for RLZ treatment, premature end of treatment (PEOT) Visit and who were in OP could complete End of Study Visit could move directly into OP in MG0007. These participants underwent their first MG0007 treatment with RLZ upon worsening of MG symptoms. Participants continued their last treatment dose from MG0004. Dose adjustments could be applied in further cycles as per Investigator's discretion. If symptom worsens between assessments, resulting in need for additional treatment, participants underwent another 6-week treatment cycle followed by OP, based on Investigator's discretion. | 80 |
| Rozanolixizumab ~10 mg/kg Eligible participants from MG0003 were randomized to receive an initial fixed 6-week treatment cycle of sc dose of RLZ equivalent to approximately 10 mg/kg QW, followed by OP that began after last dose of that treatment cycle. Eligible participants from MG0004 who completed at least 6 scheduled visits for RLZ treatment, PEOT Visit and who were in OP could complete End of Study Visit could move directly into OP in MG0007. These participants underwent their first MG0007 treatment with RLZ upon worsening of MG symptoms. Participants continued their last treatment dose from MG0004. Dose adjustments could be applied in further cycles as per Investigator's discretion. If symptom worsens between assessments, resulting in need for additional treatment, participants underwent another 6-week treatment cycle followed by OP, based on Investigator's discretion. | 77 |
| Total | 165 |
Baseline characteristics
| Characteristic | Enrolled, But Not Treated | Rozanolixizumab ~7 mg/kg | Rozanolixizumab ~10 mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 17.6 | 52.5 years STANDARD_DEVIATION 15.7 | 52.2 years STANDARD_DEVIATION 17 | 52.7 years STANDARD_DEVIATION 16.4 |
| Age, Customized 18 to <65 years | 5 Participants | 61 Participants | 57 Participants | 123 Participants |
| Age, Customized 65 to <85 years | 2 Participants | 19 Participants | 19 Participants | 40 Participants |
| Age, Customized >=85 years | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 8 Participants | 8 Participants | 16 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants | 2 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 17 Participants | 14 Participants | 32 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 3 Participants | 63 Participants | 60 Participants | 126 Participants |
| Race/Ethnicity, Customized Other/mixed | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 54 Participants | 54 Participants | 112 Participants |
| Sex: Female, Male Female | 3 Participants | 45 Participants | 48 Participants | 96 Participants |
| Sex: Female, Male Male | 5 Participants | 35 Participants | 29 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 8 | 1 / 102 | 3 / 102 |
| other Total, other adverse events | 5 / 8 | 67 / 102 | 78 / 102 |
| serious Total, serious adverse events | 3 / 8 | 16 / 102 | 31 / 102 |
Outcome results
Primary
Percentage of Participants With TEAEs Leading to Withdrawal of Investigational Medicinal Product (IMP)
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.
Time frame: From Baseline (Day 1) to End of Study (up to 34 months)
Population: Safety Set (SS): All study participants in the FAS who received at least one dose of IMP. Participants who switched doses were counted in both RLZ doses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rozanolixizumab ~7 mg/kg | Percentage of Participants With TEAEs Leading to Withdrawal of Investigational Medicinal Product (IMP) | 9.8 percentage of participants |
| Rozanolixizumab ~10 mg/kg | Percentage of Participants With TEAEs Leading to Withdrawal of Investigational Medicinal Product (IMP) | 16.7 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: From Baseline (Day 1) to End of Study (up to 34 months)
Population: Safety Set (SS): All study participants in the FAS who received at least one dose of IMP. Participants who switched doses were counted in both Rozanolixizumab (RLZ) doses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rozanolixizumab ~7 mg/kg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 78.4 percentage of participants |
| Rozanolixizumab ~10 mg/kg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 94.1 percentage of participants |
Secondary
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)
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.
Time frame: From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3)
Population: Safety Set (SS): All study participants in the FAS who received at least one dose of IMP. Number of Participants Analyzed: participants who were evaluable for the assessment. Number Analyzed included those participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rozanolixizumab ~7 mg/kg | 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) | Cycle 1: Treatment (Day 43) | -13.4 score on a scale | Standard Deviation 19.8 |
| Rozanolixizumab ~7 mg/kg | 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) | Cycle 2: Treatment (Day 43) | -10.4 score on a scale | Standard Deviation 16.2 |
| Rozanolixizumab ~7 mg/kg | 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) | Cycle 3: Treatment (Day 43) | -14.0 score on a scale | Standard Deviation 16.8 |
| Rozanolixizumab ~10 mg/kg | 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) | Cycle 1: Treatment (Day 43) | -11.6 score on a scale | Standard Deviation 16.2 |
| Rozanolixizumab ~10 mg/kg | 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) | Cycle 2: Treatment (Day 43) | -15.5 score on a scale | Standard Deviation 18.1 |
| Rozanolixizumab ~10 mg/kg | 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) | Cycle 3: Treatment (Day 43) | -13.0 score on a scale | Standard Deviation 17.9 |
Secondary
Change From Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Physical Fatigue' Score Within One Treatment Cycle (Cycle 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.
Time frame: From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3)
Population: Safety Set (SS): All study participants in FAS who received at least 1 dose of IMP. Number of Participants Analyzed: participants who were evaluable for the assessment. Number Analyzed: participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rozanolixizumab ~7 mg/kg | Change From Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Physical Fatigue' Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 1: Treatment (Day 43) | -16.5 score on a scale | Standard Deviation 18.6 |
| Rozanolixizumab ~7 mg/kg | Change From Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Physical Fatigue' Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 2: Treatment (Day 43) | -13.6 score on a scale | Standard Deviation 21.6 |
| Rozanolixizumab ~7 mg/kg | Change From Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Physical Fatigue' Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 3: Treatment (Day 43) | -15.3 score on a scale | Standard Deviation 16.9 |
| Rozanolixizumab ~10 mg/kg | Change From Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Physical Fatigue' Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 1: Treatment (Day 43) | -14.8 score on a scale | Standard Deviation 18.5 |
| Rozanolixizumab ~10 mg/kg | Change From Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Physical Fatigue' Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 2: Treatment (Day 43) | -16.0 score on a scale | Standard Deviation 18.2 |
| Rozanolixizumab ~10 mg/kg | Change From Baseline (Day 1) to Day 43 in MG Symptoms PRO 'Physical Fatigue' Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 3: Treatment (Day 43) | -15.0 score on a scale | Standard Deviation 18.4 |
Secondary
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)
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.
Time frame: From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3)
Population: Safety Set (SS): All study participants in the FAS who received at least one dose of IMP. Number of Participants Analyzed included those participants who were evaluable for the assessment. Number Analyzed included those participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rozanolixizumab ~7 mg/kg | 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) | Cycle 1: Treatment (Day 43) | -3.7 score on a scale | Standard Deviation 3.5 |
| Rozanolixizumab ~7 mg/kg | 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) | Cycle 2: Treatment (Day 43) | -2.9 score on a scale | Standard Deviation 3.1 |
| Rozanolixizumab ~7 mg/kg | 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) | Cycle 3: Treatment (Day 43) | -3.3 score on a scale | Standard Deviation 2.7 |
| Rozanolixizumab ~10 mg/kg | 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) | Cycle 1: Treatment (Day 43) | -3.1 score on a scale | Standard Deviation 2.9 |
| Rozanolixizumab ~10 mg/kg | 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) | Cycle 2: Treatment (Day 43) | -3.8 score on a scale | Standard Deviation 3.9 |
| Rozanolixizumab ~10 mg/kg | 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) | Cycle 3: Treatment (Day 43) | -3.2 score on a scale | Standard Deviation 3.3 |
Secondary
Change From Baseline (Day 1) to Day 43 in Myasthenia Gravis-Composite (MG-C) Score Within One Treatment Cycle (Cycle 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.
Time frame: From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3)
Population: Safety Set (SS): All study participants in FAS who received at least 1 dose of IMP. Number of Participants Analyzed included participants who were evaluable for the assessment. Number Analyzed included participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rozanolixizumab ~7 mg/kg | Change From Baseline (Day 1) to Day 43 in Myasthenia Gravis-Composite (MG-C) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 1: Treatment (Day 43) | -7.6 score on a scale | Standard Deviation 7.3 |
| Rozanolixizumab ~7 mg/kg | Change From Baseline (Day 1) to Day 43 in Myasthenia Gravis-Composite (MG-C) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 2: Treatment (Day 43) | -5.7 score on a scale | Standard Deviation 5.4 |
| Rozanolixizumab ~7 mg/kg | Change From Baseline (Day 1) to Day 43 in Myasthenia Gravis-Composite (MG-C) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 3: Treatment (Day 43) | -6.8 score on a scale | Standard Deviation 5.9 |
| Rozanolixizumab ~10 mg/kg | Change From Baseline (Day 1) to Day 43 in Myasthenia Gravis-Composite (MG-C) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 1: Treatment (Day 43) | -4.7 score on a scale | Standard Deviation 5.7 |
| Rozanolixizumab ~10 mg/kg | Change From Baseline (Day 1) to Day 43 in Myasthenia Gravis-Composite (MG-C) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 2: Treatment (Day 43) | -7.5 score on a scale | Standard Deviation 7 |
| Rozanolixizumab ~10 mg/kg | Change From Baseline (Day 1) to Day 43 in Myasthenia Gravis-Composite (MG-C) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 3: Treatment (Day 43) | -6.1 score on a scale | Standard Deviation 7.2 |
Secondary
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)
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.
Time frame: From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3)
Population: Safety Set (SS): All study participants in FAS who received at least 1 dose of IMP. Number of Participants Analyzed: participants who were evaluable for the assessment. Number Analyzed: participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rozanolixizumab ~7 mg/kg | 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) | Cycle 1: Treatment (Day 43) | -17.6 score on a scale | Standard Deviation 21 |
| Rozanolixizumab ~7 mg/kg | 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) | Cycle 2: Treatment (Day 43) | -13.2 score on a scale | Standard Deviation 19.2 |
| Rozanolixizumab ~7 mg/kg | 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) | Cycle 3: Treatment (Day 43) | -12.8 score on a scale | Standard Deviation 14.4 |
| Rozanolixizumab ~10 mg/kg | 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) | Cycle 1: Treatment (Day 43) | -14.6 score on a scale | Standard Deviation 17.2 |
| Rozanolixizumab ~10 mg/kg | 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) | Cycle 2: Treatment (Day 43) | -19.2 score on a scale | Standard Deviation 21.6 |
| Rozanolixizumab ~10 mg/kg | 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) | Cycle 3: Treatment (Day 43) | -15.4 score on a scale | Standard Deviation 17.7 |
Secondary
Change From Baseline (Day 1) to Day 43 in Quantitative Myasthenia Gravis (QMG) Score Within One Treatment Cycle (Cycle 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.
Time frame: From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3)
Population: Safety Set (SS): All study participants in the FAS who received at least one dose of IMP. Number of Participants Analyzed included those participants who were evaluable for the assessment. Number Analyzed included those participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rozanolixizumab ~7 mg/kg | Change From Baseline (Day 1) to Day 43 in Quantitative Myasthenia Gravis (QMG) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 1: Treatment (Day 43) | -4.5 score on a scale | Standard Deviation 5 |
| Rozanolixizumab ~7 mg/kg | Change From Baseline (Day 1) to Day 43 in Quantitative Myasthenia Gravis (QMG) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 2: Treatment (Day 43) | -3.9 score on a scale | Standard Deviation 4.1 |
| Rozanolixizumab ~7 mg/kg | Change From Baseline (Day 1) to Day 43 in Quantitative Myasthenia Gravis (QMG) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 3: Treatment (Day 43) | -5.1 score on a scale | Standard Deviation 4.8 |
| Rozanolixizumab ~10 mg/kg | Change From Baseline (Day 1) to Day 43 in Quantitative Myasthenia Gravis (QMG) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 1: Treatment (Day 43) | -4.1 score on a scale | Standard Deviation 4.2 |
| Rozanolixizumab ~10 mg/kg | Change From Baseline (Day 1) to Day 43 in Quantitative Myasthenia Gravis (QMG) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 2: Treatment (Day 43) | -4.9 score on a scale | Standard Deviation 5.5 |
| Rozanolixizumab ~10 mg/kg | Change From Baseline (Day 1) to Day 43 in Quantitative Myasthenia Gravis (QMG) Score Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 3: Treatment (Day 43) | -4.2 score on a scale | Standard Deviation 4.4 |
Secondary
MG-ADL Responder Rate (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3 [Day 43])
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 frame: Day 43 of Cycle 1, 2, and 3
Population: Safety Set (SS): All study participants in the FAS who received at least one dose of IMP. Number of Participants Analyzed included those participants who were evaluable for the assessment. Number Analyzed: participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rozanolixizumab ~7 mg/kg | MG-ADL Responder Rate (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3 [Day 43]) | Cycle 1: Treatment (Day 43) | 74.3 percentage of participants |
| Rozanolixizumab ~7 mg/kg | MG-ADL Responder Rate (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3 [Day 43]) | Cycle 2: Treatment (Day 43) | 62.5 percentage of participants |
| Rozanolixizumab ~7 mg/kg | MG-ADL Responder Rate (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3 [Day 43]) | Cycle 3: Treatment (Day 43) | 73.2 percentage of participants |
| Rozanolixizumab ~10 mg/kg | MG-ADL Responder Rate (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3 [Day 43]) | Cycle 1: Treatment (Day 43) | 63.6 percentage of participants |
| Rozanolixizumab ~10 mg/kg | MG-ADL Responder Rate (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3 [Day 43]) | Cycle 2: Treatment (Day 43) | 67.7 percentage of participants |
| Rozanolixizumab ~10 mg/kg | MG-ADL Responder Rate (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3 [Day 43]) | Cycle 3: Treatment (Day 43) | 67.2 percentage of participants |
Secondary
Time Between Consecutive Treatment Cycles
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).
Time frame: 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
Population: Safety Set (SS): All study participants in FAS who received at least 1 dose of IMP. Number Analyzed: participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 17 and Cycle 18 | 8.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 1 and Cycle 2 | 64.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 2 and Cycle 3 | 58.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 3 and Cycle 4 | 42.5 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 4 and Cycle 5 | 43.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 5 and Cycle 6 | 44.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 6 and Cycle 7 | 36.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 7 and Cycle 8 | 37.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 8 and Cycle 9 | 36.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 9 and Cycle 10 | 29.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 10 and Cycle 11 | 29.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 11 and Cycle 12 | 23.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 12 and Cycle 13 | 22.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 13 and Cycle 14 | 29.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 14 and Cycle 15 | 29.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 15 and Cycle 16 | 23.0 days |
| Rozanolixizumab ~7 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 16 and Cycle 17 | 29.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 1 and Cycle 2 | 51.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 9 and Cycle 10 | 29.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 2 and Cycle 3 | 50.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 13 and Cycle 14 | 16.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 3 and Cycle 4 | 43.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 10 and Cycle 11 | 29.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 4 and Cycle 5 | 43.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 15 and Cycle 16 | 26.5 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 5 and Cycle 6 | 43.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 11 and Cycle 12 | 22.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 14 and Cycle 15 | 9.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 7 and Cycle 8 | 37.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 12 and Cycle 13 | 22.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 8 and Cycle 9 | 36.0 days |
| Rozanolixizumab ~10 mg/kg | Time Between Consecutive Treatment Cycles | Between Cycle 6 and Cycle 7 | 43.0 days |
Secondary
Time to MG-ADL Response (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 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 frame: From Baseline (Day 1) to Day 43 of each cycle (Cycles 1, 2, and 3)
Population: Safety Set (SS): All study participants in the FAS who received at least one dose of IMP. Number Analyzed: participants who were evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rozanolixizumab ~7 mg/kg | Time to MG-ADL Response (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 1 | 9.00 days |
| Rozanolixizumab ~7 mg/kg | Time to MG-ADL Response (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 2 | 15.00 days |
| Rozanolixizumab ~7 mg/kg | Time to MG-ADL Response (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 3 | 15.00 days |
| Rozanolixizumab ~10 mg/kg | Time to MG-ADL Response (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 1 | 22.00 days |
| Rozanolixizumab ~10 mg/kg | Time to MG-ADL Response (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 2 | 15.00 days |
| Rozanolixizumab ~10 mg/kg | Time to MG-ADL Response (>=2.0-point Improvement From Baseline [Day 1]) Within One Treatment Cycle (Cycle 1, 2, and 3) | Cycle 3 | 15.00 days |