Remibrutinib for Myasthenia Gravis

(RELIEVE Trial)

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Standard-of-care treatment

Must not be taking: IVIg, Rituximab, Eculizumab, others

Disqualifiers: Thymectomy, Pregnancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

180 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you are on a stable dose of your standard-of-care treatment. It's best to discuss with the trial team to understand how your current medications fit with the study requirements.

How does the drug Remibrutinib differ from other treatments for myasthenia gravis?

Remibrutinib is unique because it targets B cells, which are part of the immune system, potentially offering a new approach compared to existing treatments like complement inhibitors and Fc receptor antagonists. This could provide a different mechanism of action for managing myasthenia gravis, which is an autoimmune condition. ^{1 2 3 4 5}

What is the purpose of this trial?

A study to evaluate the efficacy, safety and tolerability of Remibrutinib versus placebo in adult patients with Generalized Myasthenia Gravis who are on stable, standard-of-care (SOC) treatment.

Eligibility Criteria

Adults aged 18-75 with Generalized Myasthenia Gravis (gMG) can join this trial. They must have a confirmed diagnosis, not likely need a respirator during the study, and show certain symptoms. Participants should be on stable standard treatments and able to swallow pills.

Inclusion Criteria

* Confirmed diagnosis of Myasthenia Gravis Foundation of America (MGFA) Class II-IV gMG at screening and likely not in need of a respirator for the duration of the study, as judged by the Investigator * Documented evidence of positive serologic testing for AChR+ antibody or MuSK+ antibody at screening, OR seronegative for both AChR and MuSK antibodies at screening

My MG symptoms are severe, mostly not related to my eyes.

I have been on a stable dose of my current cancer treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either remibrutinib or placebo in a double-blind manner

6 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension

Participants may opt into continuation of treatment with open-label remibrutinib

Up to 60 months

Treatment Details

Interventions

• Remibrutinib

Trial Overview The trial is testing Remibrutinib's effectiveness compared to a placebo in adults with gMG who are already on standard care. Some will get Remibrutinib blindly, others a placebo, and later an open-label option for Remibrutinib is available.

Participant Groups

Group I: Remibrutinib arm Experimental Treatment 2 Interventions

Core Part: Remibrutinib tablet taken orally \[Extension Part: Open-label remibrutinib tablet taken orally\]

Group II: Placebo arm Placebo Group 2 Interventions

Core Part: Placebo tablet taken orally \[Extension Part: Open-label remibrutinib tablet taken orally\]

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

The FDA has recently approved new therapies, including complement and Fc receptor inhibitors, for treating generalized myasthenia gravis, highlighting advancements in treatment options for this condition.

There is ongoing uncertainty regarding which patients will benefit most from these expensive therapies, prompting discussions on the need for better clinical trial readiness and biomarker development to guide future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The best and worst of times in therapy development for myasthenia gravis. Benatar, M., Cutter, G., Kaminski, HJ.[2023]

Recent advancements in targeted therapies for myasthenia gravis (MG) focus on improving patient quality of life by optimizing treatment strategies, particularly for those with refractory forms of the disease.

Innovative treatments targeting B cells, complement inhibitors, and FcRn antagonists have shown positive results in clinical trials, suggesting they may enhance clinical outcomes and reduce disease burden while also considering safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Targeted Agents in Myasthenia Gravis and Future Therapeutic Strategies. Sánchez-Tejerina, D., Sotoca, J., Llaurado, A., et al.[2022]

In a study of 77 patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, rituximab treatment led to a significantly higher rate of favorable outcomes (58%) compared to controls (16%) after a median follow-up of over 3.5 years.

Rituximab-treated patients also required lower doses of prednisone (29% on 4.5 mg/day) compared to controls (74% on 13 mg/day), indicating that rituximab may reduce the need for other immunosuppressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review. Hehir, MK., Hobson-Webb, LD., Benatar, M., et al.[2018]

Ravulizumab is the first long-acting complement inhibitor approved for myasthenia gravis (MG), providing rapid and sustained complement inhibition, which is crucial for improving neuromuscular transmission.

In the CHAMPION MG trial, Ravulizumab significantly improved patients' daily living activities and clinical parameters for up to 26 weeks, with the added benefit of an administration schedule every 8 weeks, likely enhancing patient adherence and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Ravulizumab on Patient Outcomes and Quality of Life in Generalized Myasthenia Gravis. Antozzi, C., Mantegazza, R.[2023]

Efgartigimod, a first-in-class neonatal Fc receptor antagonist, received its first approval in the USA in December 2021 for treating generalized myasthenia gravis in adults who are positive for anti-acetylcholine receptor antibodies.

The drug is also being evaluated for other autoimmune diseases and has been approved in Japan for generalized myasthenia gravis patients regardless of antibody status, indicating its potential broad application in autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efgartigimod: First Approval. Heo, YA.[2022]

References

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

The best and worst of times in therapy development for myasthenia gravis. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

New Targeted Agents in Myasthenia Gravis and Future Therapeutic Strategies. [2022]

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

Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review. [2018]

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

Impact of Ravulizumab on Patient Outcomes and Quality of Life in Generalized Myasthenia Gravis. [2023]

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

Efgartigimod: First Approval. [2022]