Zilucoplan for Myasthenia Gravis

(ziMyG+ Trial)

Recruiting at 8 trial locations

Overseen By UCB Cares

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: UCB Biopharma SRL

Disqualifiers: Positive serology, Hypersensitivity, Meningococcal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

8 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the long-term safety and tolerability of an additional 52 weeks of Zilucoplan treatment administered by subcutaneous injection once daily in pediatric study participants

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 trial 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, indicating its effectiveness. A study also assessed its safety, efficacy, and tolerability in patients with this condition, supporting its use as a treatment option. ^{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, having been approved in Japan, the USA, and the EU 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, offering a new option for patients who do not respond well to traditional treatments like steroids or other immunosuppressants. ^{1 2 9 10 11}

Research Team

UCB Cares

Principal Investigator

001 844 599 2273 (UCB)

Eligibility Criteria

This trial is for pediatric patients with generalized Myasthenia Gravis who are at least 2 years old and have completed the MG0014 study. They must be willing to get booster shots against meningococcal infections if needed.

Inclusion Criteria

I am 12 years old or older and can legally consent.

I am at least 2 years old and can legally consent.

I have finished the MG0014 study and, in my doctor's view, should keep taking zilucoplan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Zilucoplan treatment administered by subcutaneous injection once daily for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Zilucoplan

Trial Overview The trial is testing Zilucoplan, a medication given by daily injection under the skin, over an additional year to see how safe and tolerable it is for long-term use in children with muscle weakness due to Myasthenia Gravis.

Participant Groups

Group I: Zilucoplan Arm Experimental Treatment 1 Intervention

Study participants will receive Zilucoplan at a pre-defined dose based on their weight.

Zilucoplan is already approved in United States, European Union for the following indications:

Approved in United States as Zilbrysq for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive

Approved in European Union as Zilbrysq for:

• Generalized myasthenia gravis in adults whose immune system produces antibodies against the acetylcholine receptor

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

Zilucoplan, a C5 inhibitor, has been approved in Japan, the USA, and the EU for treating generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive and have not responded adequately to other treatments.

This medication represents a significant advancement in gMG treatment options, particularly for patients who do not respond well to steroids or immunosuppressants, and is currently under review in Australia and Canada.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zilucoplan: First Approval. Shirley, M.[2023]

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]

About 10% of myasthenia gravis (MG) patients do not respond well to current treatments and are considered treatment refractory, with certain factors like being anti-MuSK positive or having a history of thymoma increasing this risk.

New therapies, including monoclonal antibodies like rituximab, eculizumab, and belimumab, are being proposed for patients who do not respond to standard treatments, aiming to improve outcomes for those with treatment-refractory MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies. Mantegazza, R., Antozzi, C.[2022]

In a study of 69 myasthenia gravis patients, long-term treatment with prednisolone-azathioprine (PR-AZA) significantly reduced the recurrence of myasthenic crises (MCs) from 74% in untreated patients to only 19% in treated patients over a median follow-up of 64 months.

The PR-AZA treatment also led to fewer ICU admissions and mechanical ventilation episodes, demonstrating its effectiveness in crisis prevention and improving patient outcomes after 6 months of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of combined immunosuppressive treatment on myasthenic crisis. Rózsa, C., Mikor, A., Kasa, K., et al.[2015]

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]

Ravulizumab demonstrated sustained efficacy in treating generalized myasthenia gravis over 60 weeks, with significant improvements in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores for patients who continued treatment from the randomized controlled period.

The treatment was well tolerated with no reported cases of meningococcal infections, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

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. Meisel, A., Annane, D., Vu, T., et al.[2023]

The Adverse Event Unit (AEU) was successfully implemented in a study of 54 myasthenia gravis patients, demonstrating feasibility in measuring adverse event burden, with a completion rate that met the study's primary endpoint.

Side effects were reported in 75% of patient visits, indicating a significant prevalence of adverse events, and the AEU showed a weak correlation with quality of life measures, suggesting it may be a useful tool for future comparisons of medication safety in myasthenia gravis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring treatment adverse event burden in myasthenia gravis: Single-center prospective evaluation utilizing the Adverse Event Unit (AEU). Hehir, MK., Conaway, M., St Sauveur, AB., et al.[2023]

In a study of 160 patients with steroid-insensitive myasthenia gravis, the combination of low-dose cyclophosphamide and corticosteroids was found to be effective, with 69.9% of type I patients and 64.8% of type II patients achieving significant clinical improvement after 30 weeks.

The treatment was generally safe, with only minor side effects reported, and the sensitivity to cyclophosphamide varied between types, showing higher effectiveness in type I patients compared to type II.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of low-dose cyclophosphamide plus corticosteroids for type I/II myasthenia gravis]. Feng, HY., Liu, WB., Huang, X., et al.[2013]

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]

Acetylcholinesterase inhibitors remain the first-line treatment for myasthenia gravis (MG), but their effectiveness can diminish over time, leading to the need for additional therapies.

Immunosuppressive treatments, particularly steroids and adjunctive therapies like azathioprine and mycophenolate mofetil, are crucial for managing MG symptoms, though they come with potential side effects such as renal toxicity and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Actual aspects of myasthenia gravis treatment]. Czapliński, A., Radziwiłł, AJ., Steck, AJ.[2006]

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

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

7. 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]

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]