Zilucoplan for Myasthenia Gravis

(ziMyG Trial)

Recruiting at 12 trial locations

Overseen By UCB Cares

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: UCB Biopharma SRL

Disqualifiers: Thymectomy, Systemic infection, others

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

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: 4 weeks

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests zilucoplan, a treatment for generalized myasthenia gravis (gMG), a condition that causes muscle weakness. The study aims to understand zilucoplan's behavior in the body and its safety and effectiveness for young people. Suitable participants are those under 18 with a confirmed gMG diagnosis, who struggle with daily activities due to the condition, and have been vaccinated against certain infections. As a Phase 2 trial, this research measures zilucoplan's effectiveness in an initial, smaller group of young patients, offering a chance to contribute to important advancements in gMG treatment.

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.

Is there any evidence suggesting that zilucoplan is likely to be safe for humans?

Research has shown that zilucoplan is generally safe for people with generalized myasthenia gravis (gMG). Studies found that 73% of participants felt better after taking zilucoplan, indicating its effectiveness for many. However, like any medication, it carries some risks. In one study, only one person (1.2%) experienced a serious health issue leading to death, attributed to COVID-19 rather than the treatment. Overall, evidence suggests that zilucoplan is safe for most people with gMG, with improvements often occurring quickly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Zilucoplan is unique because it targets a specific part of the immune system called the complement system, which plays a crucial role in the muscle weakness seen in myasthenia gravis. Unlike other treatments that broadly suppress the immune system, Zilucoplan offers a more targeted approach, potentially reducing side effects associated with generalized immune suppression. Researchers are excited about this treatment because it could offer a safer and more effective alternative to current therapies, such as corticosteroids and immunosuppressants, by directly addressing the underlying cause of the disease.

What evidence suggests that zilucoplan might be an effective treatment for myasthenia gravis?

Research has shown that zilucoplan, the treatment under study in this trial, effectively treats generalized myasthenia gravis (gMG). One study found that 73% of participants experienced symptom improvements after 12 weeks of treatment. Another study reported that zilucoplan enhanced patients' ability to perform daily activities, with more than a 4-point improvement. Additionally, zilucoplan provided quick and significant benefits in specific myasthenia gravis outcomes compared to a placebo. These findings suggest that zilucoplan can greatly help people with gMG. ^{2 3 4 5 6}

Who Is on the Research Team?

UCB Cares

Principal Investigator

001 844 599 2273

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Zilucoplan

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.

How Is the Trial Designed?

Group I: Zilucoplan Arm Experimental Treatment 1 Intervention

Study participants will receive zilucoplan in 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

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK616632/

Clinical Review - Zilucoplan (Zilbrysq) - NCBI Bookshelf - NIH ... Efficacy of Zilucoplan in Subjects with Generalized ... Minimal clinically important difference in myasthenia gravis: outcomes from a randomized trial.

2. zilbrysq.com zilbrysq.com/results

See the Results From the ZILBRYSQ® Clinical Trial 73% of participants receiving ZILBRYSQ experienced improvement in gMG symptoms at Week 12. 73% (63 out of 86 participants) in the 0.3 mg/kg group compared to 46 ...

3. zilbrysqhcp.com zilbrysqhcp.com/clinical-trial

ZILBRYSQ® Clinical Trial Data For gMG In the pivotal Phase 3 RAISE trial, ZILBRYSQ delivered a >4-point improvement in the ability to manage activities of daily living at Week 12 for adults with ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0022510X25001674

Efficacy of zilucoplan in patients with generalised ... Zilucoplan showed clinically meaningful improvements in myasthenia gravis (MG)-specific outcomes versus placebo in the overall population. ... Randomized trial of ...

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000208755

Effect of Zilucoplan on Myasthenia Gravis–Specific ... Zilucoplan demonstrated rapid and clinically meaningful improvements in MG-ADL and QMG total scores vs placebo in adults with acetylcholine receptor ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11025429/

Zilucoplan Safety & Efficacy in Generalized Myasthenia Gravis In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to ...