Zilucoplan for Myasthenia Gravis

(ziMyG Trial)

Recruiting in Palo Alto (17 mi)

+8 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: UCB Biopharma SRL

Disqualifiers: Thymectomy, Systemic infection, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Zilucoplan for treating myasthenia gravis?

Zilucoplan has been approved in Japan, the USA, and the EU for treating generalized myasthenia gravis in adults who are positive for anti-acetylcholine receptor antibodies and do not respond well to other treatments. A study showed that Zilucoplan is effective and well-tolerated in these patients, providing a new option for those with this challenging condition. ^{1 2 3 4 5}

Is Zilucoplan safe for humans?

Zilucoplan has been studied for safety in patients with generalized myasthenia gravis, and it is generally considered safe for use in humans, as it has been approved in several countries for this condition. ^{1 2 6 7 8}

How is the drug Zilucoplan different from other treatments for myasthenia gravis?

Zilucoplan is unique because it is a self-administered injection that specifically targets and inhibits complement component 5 (C5), a part of the immune system involved in the disease process, making it different from traditional treatments like steroids or immunosuppressants. ^{1 2 9 10 11}

Research Team

UCB Cares

Principal Investigator

001 844 599 2273

Eligibility Criteria

This trial is for children and teenagers aged 2 to less than 18 with generalized myasthenia gravis (gMG), a condition causing muscle weakness. They must have confirmed gMG through a specific blood test, show documented muscle weakness, and meet certain criteria on the MGFA Clinical Classification scale. Participants also need an up-to-date meningococcal vaccine or agree to take antibiotics until properly vaccinated.

Inclusion Criteria

My child has muscle weakness in a limb, neck, or face and is between 2 and 12 years old.

I am between 12 and 17 years old and can sign the consent form.

I am between 2 and 17 years old and can sign the consent form.

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 minimal Manifestation Status of MG based on the clinical judgement of the Investigator

I had my thymus gland removed within the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zilucoplan based on their weight to assess pharmacokinetics, pharmacodynamics, safety, tolerability, and activity

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

11 weeks

Safety-Follow-Up Visit

Treatment Details

Interventions

• Zilucoplan (Monoclonal Antibodies)

Trial Overview The study tests Zilucoplan, administered subcutaneously, to evaluate its effects on pediatric patients with gMG. It aims to understand how the drug works in young bodies (pharmacokinetics/dynamics), its safety, tolerability, potential immune response it may cause (immunogenicity), and overall effectiveness in improving symptoms.

Participant Groups

Group I: Zilucoplan Arm Experimental Treatment 1 Intervention

Study participants will receive zilucoplan in pre-defined dose based on their weight.

Who Is Running the Clinical Trial?

UCB Biopharma SRL

Lead Sponsor

Trials

118

Recruited

23,200+

Jean-Christophe Tellier

UCB Biopharma SRL

Chief Executive Officer since 2015

MD from University of Reims Champagne-Ardenne, Rheumatology specialization from University of Paris V, Executive business programs at Harvard and INSEAD

Dr. Iris Loew-Friedrich

UCB Biopharma SRL

Chief Medical Officer since 2014

MD from University of Leuven, PhD in Medical Sciences from University of Leuven

Findings from Research

In a phase 3 trial involving 174 patients with AChR-positive generalized myasthenia gravis, zilucoplan demonstrated a significant reduction in the myasthenia gravis activities of daily living (MG-ADL) score compared to placebo, indicating its efficacy as a treatment option.

Zilucoplan was generally well tolerated, with a safety profile similar to placebo, and the most common side effect was injection-site bruising, suggesting it may be a safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Howard, JF., Bresch, S., Genge, A., et al.[2023]

In a phase III trial involving 176 patients with myasthenia gravis, mycophenolate mofetil (MMF) did not show superior efficacy compared to placebo in achieving minimal manifestations or pharmacologic remission while tapering corticosteroids over 36 weeks.

Both MMF and placebo groups experienced similar rates of adverse events, indicating that MMF is well tolerated, but it did not provide additional benefits in disease control compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Sanders, DB., Hart, IK., Mantegazza, R., et al.[2022]

A new sum score has been developed to define treatment-refractory generalized myasthenia gravis (TRgMG), which includes criteria such as disease severity and inefficacy of previous therapies, making it easier for clinicians to make treatment decisions.

This scoring system, created through a consensus of 12 experts and based on a thorough literature review, aims to clarify when eculizumab should be used and can also serve as a basis for inclusion criteria in future clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Sum Score to Define Therapy-Refractory Myasthenia Gravis: A German Consensus. Schroeter, M., Berger, B., Blaes, F., et al.[2022]

In a study of 156 myasthenia gravis patients in crisis, the combination of middle-dose cyclophosphamide and methylprednisolone led to a significantly higher rate of patients being off-ventilation within 3 days (69.2%) compared to those receiving only methylprednisolone (46.2%).

The cyclophosphamide group also showed a marked reduction in pulmonary infections (21.8%) compared to the control group (67.9%), indicating that this treatment is not only effective but also safer in terms of infection risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Randomized controlled clinical trial of middle-dose cyclophosphamide plus methylprednisolone for myasthenia gravis patients in crisis]. Feng, HY., Liu, WB., Qiu, L., et al.[2013]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Zilucoplan: First Approval. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Long-term effects of combined immunosuppressive treatment on myasthenic crisis. [2015]

6. Germany pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: results from the phase 3 CHAMPION MG open-label extension. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

A Sum Score to Define Therapy-Refractory Myasthenia Gravis: A German Consensus. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Measuring treatment adverse event burden in myasthenia gravis: Single-center prospective evaluation utilizing the Adverse Event Unit (AEU). [2023]

9. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of low-dose cyclophosphamide plus corticosteroids for type I/II myasthenia gravis]. [2013]

10. China pubmed.ncbi.nlm.nih.gov

[Randomized controlled clinical trial of middle-dose cyclophosphamide plus methylprednisolone for myasthenia gravis patients in crisis]. [2013]

11. Poland pubmed.ncbi.nlm.nih.gov

[Actual aspects of myasthenia gravis treatment]. [2006]