Remibrutinib for Myasthenia Gravis
(RELIEVE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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)
Prior Safety Data
Breakthrough Therapy
Trial Summary
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.
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.
12345Eligibility 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
I am between 18 and 75 years old with generalized myasthenia gravis.
My MG symptoms are severe, mostly not related to my eyes.
+2 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Remibrutinib armExperimental Treatment2 Interventions
Core Part: Remibrutinib tablet taken orally
\[Extension Part: Open-label remibrutinib tablet taken orally\]
Group II: Placebo armPlacebo Group2 Interventions
Core Part: Placebo tablet taken orally
\[Extension Part: Open-label remibrutinib tablet taken orally\]
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Dent Neurological InstituteBuffalo, NY
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Who Is Running the Clinical Trial?
Novartis PharmaceuticalsLead Sponsor
References
The best and worst of times in therapy development for myasthenia gravis. [2023]Within the last 5 years, the US Food and Drug Administration (FDA) has approved complement and neonatal Fc receptor (FcRN) inhibitors for treatment of generalized myasthenia gravis, and several other therapies are in late-stage clinical trials or under regulatory review. However, questions about which patients are most likely to benefit from which therapies, and the relative effectiveness of these very expensive drugs, has resulted in uncertainty around the place that they should occupy in the existing therapeutic armamentarium. MGNet (a Rare Diseases Clinical Research Consortium funded by the National Institute of Neurological Diseases and Stroke) held two meetings during the 14th International Conference of the Myasthenia Gravis Foundation of America to discuss the most critical needs for clinical trial readiness and biomarker development in the context of therapy development for myasthenia gravis. Herein we provide a summary of these discussions, but not a consensus opinion, and offer a series of recommendations to guide focused research in the most critical areas. We welcome ongoing discussion through comments on this work.
New Targeted Agents in Myasthenia Gravis and Future Therapeutic Strategies. [2022]Myasthenia gravis (MG) is a chronic autoimmune disease for which multiple immunomodulatory therapies are available. Nevertheless, MG has a significant impact on patient quality of life. In recent years, experts' main efforts have focused on optimizing treatment strategies, since disease burden is considerably affected by their safety and tolerability profiles, especially in patients with refractory phenotypes. This article aims to offer neurologists caring for MG patients an overview of the most innovative targeted drugs specifically designed for this disease and summarizes the recent literature and more recent evidence on agents targeting B cells and plasmablasts, complement inhibitors, and neonatal fragment crystallizable receptor (FcRn) antagonists. Positive clinical trial results have been reported, and other studies are ongoing. Finally, we briefly discuss how the introduction of these novel targeted immunological therapies in a changing management paradigm would affect not only clinical outcomes, disease burden, safety, and tolerability, but also health spending in a condition that is increasingly managed based on a patient-centred model.
Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review. [2018]To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG).
Impact of Ravulizumab on Patient Outcomes and Quality of Life in Generalized Myasthenia Gravis. [2023]Myasthenia gravis (MG) is an autoimmune ion channel disorder in which antibodies to different end-plate antigens impair neuromuscular transmission, ultimately leading to muscle weakness and fatigability. In about 85% of patients with MG, autoantibodies against the acetylcholine receptor (AChR) activate the complement cascade, causing damage to the neuromuscular junction. MG is a chronic disorder for which standard therapies with corticosteroids, immunosuppressive drugs, and immunomodulation with plasma exchange or intravenous immunoglobulins modify the course of the disease, but the residual burden of physical, psychological, and social disability highlights several unmet needs, among these the need for specific, targeted, and well tolerated therapies able to improve the patients' quality of life. Complement inhibition paved the way to precision medicine in MG since, for the first time, a specific therapy targeting a crucial pathogenetic step has been designed, tested, and proven to be effective in a controlled fashion. Ravulizumab represents the first long-acting complement inhibitor approved for treatment of patients with generalized MG, able to provide rapid, complete, and sustained complement inhibition. Ravulizumab improved the MG Activity of Daily Living scale and other clinical parameters up to 26 weeks as shown by the CHAMPION MG trial, and by its open label extension, with the added value of being administered every 8 weeks. The schedule of administration is likely to improve patients' adherence and hence their quality of life. The introduction of complement inhibition will considerably change the traditional therapeutic strategy for MG.
Efgartigimod: First Approval. [2022]Efgartigimod (efgartigimod alfa-fcab, Vyvgart™) is a first-in-class neonatal Fc receptor antagonist being developed by argenx for the treatment of autoimmune diseases including myasthenia gravis. In December 2021, intravenous efgartigimod received its first approval in the USA for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive. Intravenous efgartigimod has also been evaluated for generalized myasthenia gravis in various other countries, with the agent subsequently approved in Japan in January 2022 for generalized myasthenia gravis patients regardless of antibody status and in preregistration stage in the EU. Several clinical studies of intravenous and subcutaneous formulation of efgartigimod are also being investigated for other autoimmune diseases including bullous pemphigoid, chronic inflammatory demyelinating polyradiculoneuropathy, immune thrombocytopenia, autoimmune myositis and pemphigus. This article summarizes the milestones in the development of efgartigimod leading to this first approval for generalized myasthenia gravis.