Zilucoplan for Myasthenia Gravis

(RAISE-XT Trial)

Not currently recruiting at 152 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: UCB Biopharma SRL

Must be taking: Zilucoplan

Disqualifiers: Other clinical trials, 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: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests zilucoplan, a medication for treating generalized Myasthenia Gravis (gMG), a condition that causes muscle weakness. The goal is to determine if zilucoplan is safe and effective over a longer period. Individuals who participated in and completed an earlier zilucoplan study may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new 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 only mentions that you must have completed a previous zilucoplan study to participate.

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 identified the most common side effects as reactions at the injection site and upper respiratory tract issues. In a long-term study with 200 participants, 32% contracted COVID-19, 29% experienced worsening of their myasthenia gravis, and 20% reported headaches. These figures provide insight into potential side effects. The treatment has been tested for over a year and a half in some cases, demonstrating its safety over a longer period. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myasthenia gravis?

Zilucoplan is unique because it targets the complement system, a part of the immune system involved in the development of myasthenia gravis. Unlike standard treatments like acetylcholinesterase inhibitors, corticosteroids, or immunosuppressants, which generally suppress the immune system or boost nerve signals, Zilucoplan specifically inhibits complement activation. This precise mechanism may reduce symptoms more effectively and with fewer side effects. Researchers are excited about its potential to offer a more targeted, efficient treatment option for patients with myasthenia gravis.

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

Research has shown that zilucoplan can help treat generalized myasthenia gravis (gMG). In one study, 73% of participants taking zilucoplan felt better within 12 weeks. Another study found that zilucoplan helped adults with gMG perform daily activities more easily. Long-term research also demonstrated significant improvements in patients' conditions. These findings suggest that zilucoplan can reduce symptoms and enhance the quality of life for people with gMG. ^{3 4 6 7 8}

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 individuals with generalized Myasthenia Gravis (gMG) who have already completed a qualifying study involving zilucoplan. They should not be part of any other clinical trials testing new treatments, although observational studies are okay.

Inclusion Criteria

You have participated in a previous study involving zilucoplan.

Exclusion Criteria

With the exception of a prior zilucoplan trial, participation in another concurrent clinical trial involving an experimental therapeutic intervention (participation in observational studies and/or registry studies is permitted)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zilucoplan and are monitored for efficacy, safety, and tolerability

12 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 36 months

Safety Follow-Up Visit

Open-label extension

Participants continue to receive zilucoplan to evaluate long-term efficacy, safety, and tolerability

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Zilucoplan

Trial Overview The RAISE-XT study is testing the long-term effects of zilucoplan on people with gMG. It's an open-label extension, meaning everyone knows they're getting zilucoplan and there's no placebo comparison.

How Is the Trial Designed?

Group I: 0.3 mg/kg zilucoplan (RA101495) Experimental Treatment 1 Intervention

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

Ra Pharmaceuticals

Lead Sponsor

Trials

8

Recruited

660+

Ra Pharmaceuticals, Inc.

Lead Sponsor

Trials

3

Recruited

390+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

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

Clinical Review - Zilucoplan (Zilbrysq) - NCBI Bookshelf - NIH In the overall gMG population, the 1 patient (1.2%) in the zilucoplan group who died experienced an SAE leading to death due to COVID-19 and COVID-19 pneumonia, ...

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

Long-term safety and efficacy of zilucoplan in patients with ... Secondary outcomes were change from baseline to Week 24 in MG-ADL, QMG, Myasthenia Gravis Composite (MGC), and the revised 15-item Myasthenia ...

6. zilbrysq.com zilbrysq.com/safety

ZILBRYSQ® Safety and Side Effects Long-term safety with ZILBRYSQ ; Side effect. All ZILBRYSQ. (200 participants) ; Side effect ; COVID-19. 32% ; Worsening myasthenia gravis. 29% ; Headache. 20%.

7. zilbrysqhcp.com zilbrysqhcp.com/safety

ZILBRYSQ® For gMG Safety And Tolerability The most common adverse reactions (reported in at least 10% of patients treated with ZILBRYSQ) were injection site reactions, upper respiratory tract ...

8. neurology.org neurology.org/doi/10.1212/WNL.0000000000204989

Long-term Safety and Efficacy of Zilucoplan in Myasthenia ... In total, 200 patients enrolled in RAISE-XT. At data cut-off (May 11, 2023), median (range) exposure to zilucoplan was 1.8 (0.11–5.1) years.