Ravulizumab for Myasthenia Gravis

Recruiting in Palo Alto (17 mi)

+25 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Alexion

Must be taking: Eculizumab

Disqualifiers: Thymic malignancy, HIV, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

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.

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.

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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.

Trial 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

Participant Groups

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.

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Research Site Boston, MA

Research Site Denton, TX

Research Site Chicago, IL

Research Site Philadelphia, PA

More Trial Locations

Who Is Running the Clinical Trial?

Alexion Lead Sponsor

Alexion Pharmaceuticals Lead Sponsor

Alexion Pharmaceuticals, Inc. Lead Sponsor

References

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

Ravulizumab for the treatment of myasthenia gravis. [2023] Myasthenia gravis (MG) is a neurological B-cell mediated autoimmune disorder affecting the neuromuscular junction. MG therapeutics have always relied on nonselective immunosuppression with oral steroids and non-steroidal immunosuppressants, mainly with good clinical response. However, clinical stabilization is often reached at the cost of many troublesome side effects and up to 15% of MG patients are deemed as refractory to conventional immunosuppression. This highlights the need of a more targeted and efficacious therapeutic approach. Results from the randomized-controlled period of the CHAMPION study demonstrate a good safety, tolerability, and efficacy profile of ravulizumab compared to placebo. Like eculizumab, ravulizumab is an anti-C5 monoclonal antibody, but with an enhanced pharmacokinetic profile, that allows dosing every 8 weeks.

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] The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension.

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

Ravulizumab: A Review in Generalised Myasthenia Gravis. [2023] Ravulizumab (ULTOMIRIS&#174;) is the first long-acting complement C5 inhibitor (administered intravenously every 8 weeks) to be approved in several countries globally, for adults with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor antibody-positive (AChR Ab+). In the phase III CHAMPION MG trial, intravenous ravulizumab was associated with statistically significant improvements in the MG-Activities of Daily Living scale at week 26 of treatment compared with placebo in adults with AChR Ab+ gMG. Improvements in the Quantitative MG scale total score were also statistically significantly higher in ravulizumab than placebo recipients. These improvements were sustained to week 26 of treatment. Ravulizumab was generally well tolerated; the most common treatment-emergent adverse events were headache, diarrhoea and nausea. Efficacy and tolerability data for up to 1 year from the ongoing open-label extension phase are consistent with those from the randomized, placebo-controlled phase; further results are awaited with interest. Thus, ravulizumab is an efficacious, generally well tolerated and convenient treatment option in adults with AChR Ab+ gMG, expanding the options available for gMG management.

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

A Sum Score to Define Therapy-Refractory Myasthenia Gravis: A German Consensus. [2022] In 2017, eculizumab has been approved for treatment-refractory generalised myasthenia gravis (TRgMG). The German Myasthenia Foundation has published a consensus statement on the use of eculizumab, with a recent update. However, a treatment-refractory state is still ill-defined and the term warrants further clarification. We aimed at developing a sum score to operationalise the definition of a TRgMG status, which is easy- to-handle in clinical decision making.

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] Ravulizumab demonstrated efficacy and an acceptable safety profile versus placebo in the randomized controlled period (RCP) of the phase 3 CHAMPION MG trial in patients with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. We report an interim analysis of the ongoing open-label extension (OLE) designed to evaluate long-term treatment effects.