Ravulizumab for Myasthenia Gravis

Recruiting at 23 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion

Must be taking: Eculizumab

Disqualifiers: Thymic malignancy, HIV, 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: 1

Duration: 122 weeks

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants be on a stable dosing regimen of their current medications before and during the screening period, so you will not need to stop taking them.

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

Ravulizumab has shown significant improvements in daily living activities and overall symptoms in patients with generalized myasthenia gravis, as demonstrated in the phase III CHAMPION MG trial. These improvements were sustained over 26 weeks, and the drug was generally well tolerated, making it a promising treatment option for this condition. ^{1 2 3 4 5}

What is the purpose of this trial?

The primary purpose of this study is to characterize the pharmacokinetics and pharmacodynamics of treatment with ravulizumab intravenous infusion in pediatric participants with gMG.

Eligibility Criteria

This trial is for children with generalized Myasthenia Gravis (gMG) who are classified as Class II to IV. They must be on a stable treatment regimen, vaccinated against meningococcal infection, and if previously treated with eculizumab, they should have been on it for at least 6 months. Those with HIV, recent thymic surgery or untreated thymic malignancy cannot participate.

Inclusion Criteria

My current medication dose has been stable before and during the screening.

I have been treated with eculizumab for at least 6 months and on a stable dose for 2 months.

My myasthenia gravis is moderate to severe.

Exclusion Criteria

I have an untreated cancer in my thymus.

I have had infections that doctors couldn't explain.

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a weight-based loading dose of ravulizumab IV on Day 1, followed by maintenance doses every 8 weeks or 4 weeks based on weight, for a total of 122 weeks

122 weeks

Initial visit on Day 1, followed by visits every 4 or 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ravulizumab

Trial Overview The study tests Ravulizumab given through an IV in pediatric patients with gMG. It aims to understand how the drug moves and acts within the body (pharmacokinetics/pharmacodynamics), its effectiveness, safety profile, and potential immune response it may cause.

Participant Groups

Group I: Ravulizumab Intravenous (IV) Infusion Experimental Treatment 1 Intervention

All participants will receive a weight-based loading dose of ravulizumab IV on Day 1, followed by weight-based maintenance dose of ravulizumab on Day 15 and once every 8 weeks (q8w) thereafter for participants weighing ≥ 20 kg, or once every 4 weeks (q4w) for participants weighing \< 20 kg, for a total of 122 weeks of treatment.

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

Approved in United States as Ultomiris for:

• Paroxysmal nocturnal hemoglobinuria (PNH)
• Atypical hemolytic uremic syndrome (aHUS)

Approved in European Union as Ultomiris for:

• Paroxysmal nocturnal haemoglobinuria (PNH)

Who Is Running the Clinical Trial?

Alexion

Lead Sponsor

Trials

247

Recruited

38,600+

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Alexion Pharmaceuticals

Lead Sponsor

Trials

231

Recruited

36,700+

Marc Dunoyer

Alexion Pharmaceuticals

Chief Executive Officer since 2021

B.A. in Psychology from the University of New Hampshire

Christophe Hotermans

Alexion Pharmaceuticals

Chief Medical Officer since 2023

MD

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Findings from Research

Ravulizumab, an anti-C5 monoclonal antibody, has shown a good safety and efficacy profile in treating generalized myasthenia gravis (MG) in the phase III CHAMPION study, which suggests it could be a promising alternative to conventional immunosuppressants.

Unlike traditional treatments that require frequent dosing, ravulizumab can be administered every 8 weeks, providing a more convenient option for patients while maintaining a rapid and long-term clinical response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab for the treatment of myasthenia gravis. Vanoli, F., Mantegazza, R.[2023]

In a 26-week phase 3 study, eculizumab significantly improved symptoms in patients with refractory generalized myasthenia gravis (gMG), with 21.4% of treated patients achieving 'minimal symptom expression' compared to only 1.7% in the placebo group.

The benefits of eculizumab were sustained over a 130-week open-label extension, showing that patients who initially received placebo also achieved similar symptom relief after starting eculizumab, indicating its long-term efficacy and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'Minimal symptom expression' in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab. Vissing, J., Jacob, S., Fujita, KP., et al.[2021]

Ravulizumab is the first long-acting complement C5 inhibitor approved for adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor antibody-positive, showing significant improvements in daily living activities and muscle strength compared to placebo in the phase III CHAMPION MG trial.

The treatment was generally well tolerated, with common side effects including headache, diarrhea, and nausea, and its efficacy was sustained over 26 weeks, making it a convenient option for managing gMG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: A Review in Generalised Myasthenia Gravis. Kang, C.[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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ravulizumab for the treatment of myasthenia gravis. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

'Minimal symptom expression' in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab. [2021]

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

Ravulizumab: A Review in Generalised Myasthenia Gravis. [2023]

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

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

5. 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]