Generalized Myasthenia Gravis
Conditions
Keywords
gMG
Brief summary
The purpose of the study is to evaluate the safety and tolerability of switching from intravenous (IV) complement component 5 (C5) inhibitors to subcutaneous (SC) Zilucoplan in study participants with generalized myasthenia gravis (gMG)
Interventions
Subcutaneous injection
Sponsors
UCB Biopharma SRL
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Participant has been treated with an intravenous (IV) complement component 5 (C5) inhibitor approved for the treatment of generalized myasthenia gravis (gMG) at the recommended dose regimen for at least 3 months (for eculizumab) or 4 months (for ravulizumab) prior to Screening with a clinically stable disease as per the Investigator's judgment. * Participant is willing to switch from his/her current IV C5 inhibitor to subcutaneous (SC) zilucoplan (ZLP) * Participant has a documented diagnosis of gMG (Myasthenia Gravis Foundation of America; MGFA Class II-IVa) at Screening based on participant history and supported by previous evaluations * Participant has a well-documented record of positive serology for acetylcholine receptor binding autoantibodies prior to Screening * Participant has no more than a 2-point change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Baseline compared with the Screening Visit * Participant has had no change in corticosteroid dose during the Screening Period and no change in corticosteroid dose is anticipated to occur during the 12-week Main Treatment Period * Participant has had no change in immunosuppressive therapy, including dose, during the Screening Period and no change in immunosuppressive therapy is anticipated to occur during the 12-week Main Treatment Period * Participant has a record of vaccination with at least 1 dose of a quadrivalent meningococcal vaccine and meningococcal serotype B vaccine at least 14 days prior to the first dose of ZLP if not vaccinated within 3 years prior to the start of study medication * Male and/or female * A male participant is recommended to agree to use contraception during the study and for at least 40 days (5 half lives) after the last dose of study medication, and refrain from donating sperm during this period. * A female participant is eligible to participate if she is not pregnant; not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) OR * A WOCBP who agrees to follow the contraceptive guidance during the study and for at least 40 days (5 half lives) after the last dose of study medication. * Participant is capable of giving signed informed consent
Exclusion criteria
* Participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the participant's ability to participate in this study * Participant has a known hypersensitivity to any components of the study medication as stated in this protocol * Participant has had a thymectomy within 6 months prior to Baseline or has one scheduled to occur during the 12-week Main Treatment Period * Participant has a history of meningococcal disease * Participant has or has had a current or recent systemic infection within 2 weeks prior to Baseline or an infection requiring IV antibiotics within 4 weeks prior to Baseline * Participant has active malignancy (except curatively resected squamous or basal cell carcinoma of the skin) requiring surgery, chemotherapy, or radiation within the prior 12 months (participants with a history of malignancy who have undergone curative resection or otherwise not requiring treatment for at least 12 months prior to Screening with no detectable recurrence are allowed). * Participant has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has had suicidal ideation with at least some intent to act in the past 6 months as indicated by a positive response (Yes) to either question 4 or question 5 of the Screening/Baseline version of the C-SSRS at Screening. * Participant has alanine transaminase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) \>2.5x upper limit of normal (ULN) * Participant has bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Participant has current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. * QTc interval \>450msec for male participants, QTc \>470msec for female participants, or QTc \>480 msec in participants with bundle branch block * Participant has had recent surgery requiring general anesthesia within 2 weeks prior to Screening or is expected to have surgery requiring general anesthesia during the 12-week Main Treatment Period * Participant has received a treatment with an experimental drug within 30 days or 5 half lives of the experimental drug (whichever is longer) prior to Baseline * Participant has received treatment with rituximab within 6 months prior to Baseline or treatment is planned to occur during the study * Participant has received treatment with intravenous immunoglobulin G (IVIG), SC immunoglobulin, or plasma exchange PLEX 4 weeks prior to Baseline or participant is on chronic IVIG, SC immunoglobulin, or PLEX * Participant has previously participated in this study or participant has previously been assigned to treatment in a study of the medication under investigation in this study * Participant has participated in another study of an investigational study medication (and/or an investigational device) within the previous 30 days or is currently participating in another study of an investigational study medication (and/or an investigational device) * Participant has known positive serology for muscle-specific kinase
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Main Treatment Period | From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks) | An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. A TEAE was defined as an AE starting on or after the time of first administration of investigational medicinal product (IMP) and up to and including 40 days after the final dose (or last contact depending on which occurs first). |
| Percentage of Participants With TEAEs Leading to Withdrawal of Study Medication Over the Main Treatment Period | From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks) | An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. A TEAE was defined as an AE starting on or after the time of first administration of IMP and up to and including 40 days after the final dose (or last contact depending on which occurs first). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | From Baseline to Week 12 | The MG-ADL is a brief 8-item interviewer-administered patient-reported outcome (PRO) designed to evaluate MG symptom severity. The MG-ADL targets symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. Each item is assessed on a 4-point scale, where a score of 0 represents normal function and a score of 3 represents severely decreased ability to perform that function. The total MG-ADL score ranges from 0 to 24, with a higher score indicating more severe impairment. A positive change in score indicates worsening and negative change indicates improvement. |
| Change From Baseline to Week 12 in the Quantitative Myasthenia Gravis (QMG) Score | From Baseline to Week 12 | The QMG is a standardized and validated quantitative strength scoring system that included 13 items in the following categories: ocular and facial involvement, swallowing, speech, limb strength, and forced vital capacity. Scoring for each item ranges from no weakness (0) to severe weakness (3), with an overall score range from 0 to 39. Higher scores represent more severe impairment. A positive change in score indicates worsening and negative change indicates improvement. |
| Percentage of Participants With Serious TEAEs Over the Main Treatment Period | From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks) | Treatment-emergent serious adverse events (serious TEAEs) were any untoward medical incidence in a participant during administered study treatment, whether or not these events were related to study treatment and additionally were emergent untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Required in patient hospitalisation or prolongation of existing hospitalisation * Results in persistent disability/incapacity * Was a congenital anomaly or birth defect * Important medical events |
| Percentage of Participants With Study Withdrawal Over the Main Treatment Period | From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks) | Percentage of participants with study withdrawal based to pre-defined reasons in the protocol were reported. |
Countries
United States
Participant flow
Recruitment details
The study started to enroll participants in October 2022 and concluded in October 2024.
Pre-assignment details
Participant Flow refers to the modified Intention to Treat Population (mITT).
Participants by arm
| Arm | Count |
|---|---|
| Zilucoplan 0.3 mg/kg Participants were administered zilucoplan (ZLP) 0.3 milligrams per kilogram per day (mg/kg/day) subcutaneously (SC) once daily (QD) for 12 weeks in Main Treatment Period. Participants who completed the 12-week Main Treatment Period without discontinuing study medication, continued to receive ZLP 0.3 mg/kg/day, SC, once daily in the Extension Treatment Period (up to approximately 84 weeks) until ZLP was commercially available or until further notice from the Sponsor. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Treatment Period | Lost to Follow-up | 3 |
| Main Treatment Period | Adverse Event | 2 |
| Main Treatment Period | Subject's lack of compliance with study procedures | 1 |
Baseline characteristics
| Characteristic | Zilucoplan 0.3 mg/kg |
|---|---|
| Age, Continuous | 59.9 years STANDARD_DEVIATION 15.9 |
| Age, Customized 18 - <65 years | 12 Participants |
| Age, Customized 65 - <85 years | 14 Participants |
| Age, Customized >=85 years | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 22 Participants |
| Race/Ethnicity, Customized Other or Mixed | 2 Participants |
| Race/Ethnicity, Customized White | 19 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 24 / 26 |
| serious Total, serious adverse events | 5 / 26 |
Outcome results
Primary
Percentage of Participants With TEAEs Leading to Withdrawal of Study Medication Over the Main Treatment Period
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. A TEAE was defined as an AE starting on or after the time of first administration of IMP and up to and including 40 days after the final dose (or last contact depending on which occurs first).
Time frame: From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks)
Population: The SS included all study participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilucoplan 0.3 mg/kg | Percentage of Participants With TEAEs Leading to Withdrawal of Study Medication Over the Main Treatment Period | 7.7 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Main Treatment Period
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. A TEAE was defined as an AE starting on or after the time of first administration of investigational medicinal product (IMP) and up to and including 40 days after the final dose (or last contact depending on which occurs first).
Time frame: From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks)
Population: The Safety Set (SS) included all study participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilucoplan 0.3 mg/kg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Main Treatment Period | 73.1 percentage of participants |
Secondary
Change From Baseline to Week 12 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score
The MG-ADL is a brief 8-item interviewer-administered patient-reported outcome (PRO) designed to evaluate MG symptom severity. The MG-ADL targets symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. Each item is assessed on a 4-point scale, where a score of 0 represents normal function and a score of 3 represents severely decreased ability to perform that function. The total MG-ADL score ranges from 0 to 24, with a higher score indicating more severe impairment. A positive change in score indicates worsening and negative change indicates improvement.
Time frame: From Baseline to Week 12
Population: The modified ITT Population (mITT) population included all eligible study participants who received at least 1 post-Baseline dose of study medication and had at least 1 post-Baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zilucoplan 0.3 mg/kg | Change From Baseline to Week 12 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score | -1.15 score on a scale |
p-value: <0.001Mixed Model for Repeated Measures (MMRM)
Secondary
Change From Baseline to Week 12 in the Quantitative Myasthenia Gravis (QMG) Score
The QMG is a standardized and validated quantitative strength scoring system that included 13 items in the following categories: ocular and facial involvement, swallowing, speech, limb strength, and forced vital capacity. Scoring for each item ranges from no weakness (0) to severe weakness (3), with an overall score range from 0 to 39. Higher scores represent more severe impairment. A positive change in score indicates worsening and negative change indicates improvement.
Time frame: From Baseline to Week 12
Population: The mITT population included all eligible study participants who received at least 1 post-Baseline dose of study medication and had at least 1 post-Baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zilucoplan 0.3 mg/kg | Change From Baseline to Week 12 in the Quantitative Myasthenia Gravis (QMG) Score | -1.24 score on a scale |
Secondary
Percentage of Participants With Serious TEAEs Over the Main Treatment Period
Treatment-emergent serious adverse events (serious TEAEs) were any untoward medical incidence in a participant during administered study treatment, whether or not these events were related to study treatment and additionally were emergent untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Required in patient hospitalisation or prolongation of existing hospitalisation * Results in persistent disability/incapacity * Was a congenital anomaly or birth defect * Important medical events
Time frame: From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks)
Population: The SS included all study participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilucoplan 0.3 mg/kg | Percentage of Participants With Serious TEAEs Over the Main Treatment Period | 3.8 percentage of participants |
Secondary
Percentage of Participants With Study Withdrawal Over the Main Treatment Period
Percentage of participants with study withdrawal based to pre-defined reasons in the protocol were reported.
Time frame: From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks)
Population: The mITT population included all eligible study participants who received at least 1 post-Baseline dose of study medication and had at least 1 post-Baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilucoplan 0.3 mg/kg | Percentage of Participants With Study Withdrawal Over the Main Treatment Period | 11.5 percentage of participants |