An Open-label Study to Evaluate the Safety, Tolerability, and Efficacy of Subcutaneous Zilucoplan in Participants With Generalized Myasthenia Gravis Who Were Previously Receiving Intravenous Complement Component 5 Inhibitors

• ClinicalTrials.gov Identifier: NCT05514873
• Recruitment Status: Recruiting
• First Posted: August 25, 2022
• Last Update Posted: March 17, 2023
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Generalized Myasthenia Gravis	Drug: zilucoplan (RA101495)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, Multicenter, Open-Label, Single-Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Zilucoplan in Participants With Generalized Myasthenia Gravis Switching From Intravenous Complement Component 5 Inhibitors to Subcutaneous Zilucoplan
• Actual Study Start Date: October 31, 2022
• Estimated Primary Completion Date: January 15, 2024
• Estimated Study Completion Date: January 15, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: 0.3 mg/kg zilucoplan (RA101495); Study participants will be treated with subcutaneous zilucoplan (0.3mg/kg/day)	Drug: zilucoplan (RA101495); Subcutaneous injection

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment-emergent adverse events (TEAEs) over the Main Treatment Period [ Time Frame: From Baseline (Day 1) to Safety Follow-Up Visit of Main Treatment Period (up to Week 18) ]
   Treatment-emergent adverse events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment.
2. Incidence of treatment-emergent adverse events (TEAEs) leading to withdrawal of study medication over the Main Treatment Period [ Time Frame: From Baseline (Day 1) to Safety Follow-Up Visit of Main Treatment Period (up to Week 18) ]
   Treatment-emergent adverse events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment.

Secondary Outcome Measures :

1. Change from Baseline to Week 12 in MG ADL score [ Time Frame: From Baseline to Week 12 ]
   The Myasthenia Gravis-Activities of Daily Living (MG-ADL) profile provides an assessment of myasthenia gravis (MG) symptom severity and measures 8 items on a 0-3 scale, with 0 being the least severe. The total sum of the 8 items represents the MG-ADL score. The MG-ADL score can range from 0 (least severe) to 24 (most severe).
2. Change from Baseline to Week 12 in the QMG score [ Time Frame: From Baseline to Week 12 ]
   The Quantitative Myasthenia Gravis (QMG) is a standardized and validated quantitative strength scoring system and measures 13 items on a 0-3 scale, with 0 being the least severe. The total sum of the 13 items represents the QMG score. The QMG score can range from 0 (least severe) to 39 (most severe)
3. Incidence of serious treatment-emergent adverse events (serious TEAEs) over the Main Treatment Period [ Time Frame: From Baseline (Day 1) to Safety Follow-Up Visit of Main Treatment Period (up to Week 18) ]

   Treatment-emergent serious adverse events (serious TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment and additionally are emergent untoward medical occurrence that at any dose:

   • Results in death
   • Is life-threatening
   • Requires in patient hospitalisation or prolongation of existing hospitalisation
   • Results in persistent disability/incapacity
   • Is a congenital anomaly or birth defect
   • Important medical events
4. Incidence of study withdrawal over the Main Treatment Period [ Time Frame: From Baseline (Day 1) to End of Treatment Period (up to 12 weeks) ]
   Incidence of study withdrawals based to pre-defined reasons in the Protocol.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: UCB Cares; 001-844-599-2273 (USA); ucbcares@ucb.com

Contact: UCB Cares; 001 844 599 2273

Locations

United States, Florida

Mg0017 50558; Recruiting

Miami, Florida, United States, 33144

United States, Georgia

Mg0017 50075; Recruiting

Augusta, Georgia, United States, 30912

United States, Illinois

Mg0017 50557; Recruiting

O'Fallon, Illinois, United States, 62269

United States, Ohio

Mg0017 50076; Recruiting

Columbus, Ohio, United States, 43221

United States, Texas

Mg0017 50555; Completed

Austin, Texas, United States, 78759

Sponsors and Collaborators

UCB Biopharma SRL

Investigators

• Study Director: UCB Cares; 001 844 599 2273

More Information

• Responsible Party: UCB Biopharma SRL
• ClinicalTrials.gov Identifier: NCT05514873
• Other Study ID Numbers: MG0017
• First Posted: August 25, 2022
• Last Update Posted: March 17, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed.All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• URL: https://www.Vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by UCB Pharma ( UCB Biopharma SRL ):

gMG

Additional relevant MeSH terms:

Myasthenia Gravis; Muscle Weakness; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases