A Study to Evaluate Subcutaneous Zilucoplan in Pediatric Participants With Generalized Myasthenia Gravis (ziMyG)

• ClinicalTrials.gov Identifier: NCT06055959
• Recruitment Status: Recruiting
• First Posted: September 28, 2023
• Last Update Posted: May 14, 2024
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

Study Description

Brief Summary:

The purpose of this study is to assess the pharmacokinetics, pharmacodynamics, safety, tolerability, immunogenicity and activity of zilucoplan (ZLP) in pediatric study participants with generalized myasthenia gravis (gMG).

Condition or disease	Intervention/treatment	Phase
Generalized Myasthenia Gravis	Drug: Zilucoplan	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Open-Label, Uncontrolled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Activity of Zilucoplan in Pediatric Study Participants From 2 to Less Than 18 Years of Age With Acetylcholine Receptor Antibody Positive Generalized Myasthenia Gravis
• Estimated Study Start Date: June 11, 2024
• Estimated Primary Completion Date: October 26, 2026
• Estimated Study Completion Date: December 4, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Zilucoplan Arm; Study participants will receive zilucoplan in pre-defined dose based on their weight.	Drug: Zilucoplan; Zilucoplan will be administered subcutaneously to pediatric study participants.; Other Name: RA101495

Outcome Measures

Primary Outcome Measures :

1. Plasma concentrations of zilucoplan (ZLP) sampled at Week 4 (Day 29) [ Time Frame: Week 4 (Day 29) ]
   Blood samples will be collected for measurement of plasma concentrations of ZLP on Day 29 predose.
2. Change from Baseline in sheep red blood cell (sRBC) lysis at Week 4 (Day 29) [ Time Frame: Week 4 (Day 29) ]
   Samples for measurement of sRBC lysis will be collected on Day 29 predose.
3. Change from Baseline in complement component 5 (C5) levels at Week 4 (Day 29) [ Time Frame: Week 4 (Day 29) ]
   Samples for measurement of C5 will be collected on Day 29 predose.

Secondary Outcome Measures :

1. Occurence of treatment-emergent adverse events (TEAEs) during the course of the study [ Time Frame: From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15) ]
   An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have 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.
2. Occurrence of treatment-emergent serious adverse events (TESAEs) [ Time Frame: From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15) ]

   A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose:

   Results in death Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent disability/incapacity Is a congenital anomaly/birth defect Important medical events

3. Occurrence of TEAEs leading to permanent withdrawal of investigational medicinal product (IMP) [ Time Frame: From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15) ]
   An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs leading to permanent withdrawal of study medication.
4. Occurrence of treatment-emergent infections [ Time Frame: From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15) ]

   Percentage of participants who experienced treatment-emergent infections as adverse events.

   An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.

5. Occurrence of antidrug antibody (ADA) and anti- polyethylene glycol (PEG) antibodies at Week 4 (Day 29) [ Time Frame: Week 4 (Day 29) ]
   ADA and anti-PEG antibodies will be evaluated in serum samples.
6. Change in MG-activities of daily living (MG-ADL) score from Baseline to Week 4 (Day 29). [ Time Frame: Week 4 (Day 29) ]
   The MG-ADL score is an 8-item patient-reported outcome (PRO) instrument. The MG-ADL targets symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The item responses are scored from 0 to 3, and the total score of MG-ADL is the sum of the 8 items and ranges from 0 to 24, with a higher score indicating more disability.
7. Change in Quantitative MG (QMG) score from Baseline to Week 4 (Day 29) [ Time Frame: Week 4 (Day 29) ]
   QMG score is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The QMG total score is obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity.
8. Myasthenia Gravis Foundation of America Post-Interventional Status (MGFA-PIS) at Week 4 (Day 29) [ Time Frame: Week 4 (Day 29) ]
   The MGFA-PIS is a physician-determined assessment of clinical symptoms of MG after initiation of MG specific therapy. For the purpose of the current study, Minimal Manifestation will be determined at each scheduled time point after treatment initiation (rather than after 1 year). Change in status (improved, unchanged, worse, exacerbation, or died of MG) will also be determined.
9. Change in Pediatric Quality of Life Inventory (PedsQoL), Version 4 domain scores from Baseline to Week 4 (Day 29) [ Time Frame: Week 4 (Day 29) ]
   The PedsQoL generic core scale (Version 4) is a validated instrument that is suitable for use with pediatric populations. PedsQoL generic core scales assess Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. The scale has 23 items with a score range of 0 to 4. Following transformation, the score range of each domain as well as the total score is 0-100 with higher scores indicating higher HRQoL.

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

United States of America (USA) specific inclusion criterion:

- Participant must be 12 to <18 years of age at the time of signing the Informed consent/assent according to local regulation

Rest of world (ROW) specific inclusion criterion:

- Participant must be 2 to <18 years of age at the time of signing the Informed consent/assent according to local regulation

Global inclusion criteria:

• Participant has a diagnosis of generalized myasthenia gravis (gMG) confirmed by a prior positive serologic test result to acetylcholine receptor (AChR) prior to Screening
• Participant meets the criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification II to IV at Screening
• Participants with gMG, including:
• An MG-activities of daily living (MG-ADL) total score of 6 or more in adolescents from 12 years to <18 years of age at Screening
• Documented weakness in at least 1 limb, neck, or bulbar muscle in children from 2 years to <12 years of age at Screening (does not apply to US)
• Documented vaccination against meningococcal infections within 3 years prior to study start. If not fully vaccinated, participants must receive appropriate prophylactic antibiotic treatment until at least 2 weeks after the initial dose of vaccine(s)

Exclusion Criteria:

• Participant has known positive serology for muscle-specific kinase
• 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 had a thymectomy within 6 months prior to Baseline
• Participant has minimal Manifestation Status of MG based on the clinical judgement of the Investigator
• Current or recent systemic infection within 2 weeks prior to Baseline or infection requiring intravenous antibiotics within 4 weeks prior to Baseline

Contacts and Locations

Contacts

Contact: UCB Cares; +18445992273 (USA); ucbcares@ucb.com

Contact: UCB Cares; 001 844 599 2273

Locations

United States, Texas

Mg0014 50574; Recruiting

Denton, Texas, United States, 76208

Italy

Mg0014 40144; Recruiting

Milano, Italy

Korea, Republic of

Mg0014 20104; Recruiting

Seoul, Korea, Republic of

Mg0014 20220; Recruiting

Seoul, Korea, Republic of

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: NCT06055959
• Other Study ID Numbers: MG0014; U1111-1290-3349 ( Other Identifier: WHO universal trial number (UTN) ); 2022-502072-23-00 ( Registry Identifier: EU CT Number )
• First Posted: September 28, 2023
• Last Update Posted: May 14, 2024
• Last Verified: May 2024

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 study 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: http://www.Vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by UCB Pharma ( UCB Biopharma SRL ):

RA101495; gMG; generalized myasthenia gravis; zilucoplan; pediatric; MG0014

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