Remibrutinib for Myasthenia Gravis

(RELIEVE Trial)

Recruiting at 68 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Remibrutinib for individuals with Generalized Myasthenia Gravis (gMG), a condition that causes muscle weakness. The researchers aim to determine if Remibrutinib is safe, effective, and better tolerated than a placebo (an inactive pill) in patients already on a stable dose of standard treatment. Suitable participants have been living with gMG, experience symptoms beyond just eye problems, and have had the condition confirmed by specific tests. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

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.

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

Research has shown that Remibrutinib has been safe in past studies for autoimmune disorders. Most participants did not experience serious side effects, even with up to 52 weeks of use.

In various trials, Remibrutinib was safe and well-tolerated at different doses. This includes studies on conditions like Chronic Spontaneous Urticaria (CSU) and Multiple Sclerosis (MS). These findings suggest that the treatment is generally safe for people.

Although Remibrutinib is not yet approved for Myasthenia Gravis, its safety in other conditions supports ongoing trials to test its use. Since this trial is in a later phase, earlier studies have already assessed its safety, providing further reassurance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Myasthenia Gravis?

Remibrutinib is unique because it targets the Bruton's tyrosine kinase (BTK) pathway, which is a different mechanism of action compared to current treatments for myasthenia gravis that typically involve immunosuppressants or acetylcholinesterase inhibitors. Most current treatments aim to broadly suppress the immune system or enhance nerve-muscle communication, but remibrutinib specifically interferes with the signaling processes that lead to the immune attack on muscles. This targeted approach could potentially lead to fewer side effects and more effective symptom management. Researchers are excited about remibrutinib because it might offer a more precise treatment option with faster onset of action and improved patient outcomes.

What evidence suggests that Remibrutinib might be an effective treatment for Myasthenia Gravis?

Research has shown that Remibrutinib, which participants in this trial may receive, delivers promising results for some autoimmune conditions. In individuals with chronic spontaneous urticaria (CSU), Remibrutinib acted quickly and effectively for a full year. Although CSU differs from myasthenia gravis, these results suggest it might alleviate autoimmune symptoms. The treatment has consistently demonstrated safety, making it a promising candidate for further study in generalized myasthenia gravis. These findings support the potential of Remibrutinib to manage symptoms in myasthenia gravis by targeting similar immune pathways. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06744920

NCT06744920 | A Study to Investigate the Efficacy, Safety ... A study to evaluate the efficacy, safety and tolerability of Remibrutinib versus placebo in adult patients with Generalized Myasthenia Gravis who are on stable, ...

2. neurologylive.com neurologylive.com/view/new-phase-3-study-evaluate-remibrutinib-generalized-myasthenia-gravis-treatment

New Phase 3 Study to Evaluate Remibrutinib in ... A phase 3 study evaluates remibrutinib's safety and efficacy for generalized myasthenia gravis, promising new treatment options for patients.

3. novartis.com novartis.com/clinicaltrials/study/nct06744920

A Study to Investigate the Efficacy, Safety and Tolerability ... A study to evaluate the efficacy, safety and tolerability of Remibrutinib versus placebo in adult patients with Generalized Myasthenia Gravis

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37866460/

Remibrutinib demonstrates favorable safety profile and ... Remibrutinib demonstrated a consistent favorable safety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU.

5. ucihealth.org ucihealth.org/clinical-trials/ccr-23-99

Phase III study to evaluate remibrutinib in patients ... c. Patient has demonstrated improvement in MG signs on oral acetylcholinesterase inhibitors as assessed by the treating physician. other ...

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000202933

Remibrutinib: A Novel BTKi in Development for MS With ... Conclusions: Remibrutinib demonstrated a favorable safety profile and was well tolerated at all doses studied in Phase 2 trials and the OLE (up to 100 mg b.i.d.) ...