What side effects are associated with this type of intervention?

Common treatments for Myasthenia Gravis include acetylcholinesterase inhibitors, immunotherapy, and emerging cell therapies like MuSK-CAART. Acetylcholinesterase inhibitors, such as pyridostigmine, can cause gastrointestinal side effects like diarrhea, nausea, and abdominal cramps, as well as muscarinic side effects like increased salivation and sweating. Immunotherapy, including glucocorticoids and nonsteroidal immunosuppressive agents, can lead to side effects such as weight gain, hypertension, diabetes, and increased risk of infections. Cell therapies targeting pathogenic autoantibodies, like MuSK-CAART, are still under investigation, but potential side effects may include infusion reactions, cytokine release syndrome, and increased susceptibility to infections due to immune modulation.

What prior FDA approvals exist?

The FDA has approved several treatments for Myasthenia Gravis, primarily focusing on immunosuppressive therapies and symptomatic treatments. Rituximab, an anti-CD20 monoclonal antibody, has shown efficacy in MuSK-positive MG by targeting B-cells that produce pathogenic antibodies. Eculizumab, a complement inhibitor, is another FDA-approved drug that reduces the activity of the immune system's complement pathway, which is involved in the destruction of the neuromuscular junction in MG. These treatments, while not identical to the cell therapy MuSK-CAART, share the common goal of targeting the underlying autoimmune mechanisms of the disease.

What other types of research exist?

Promising novel alternatives to MuSK-CAART for Myasthenia Gravis patients include: 1) Intravenous immunoglobulin (IVIg), which has shown efficacy in reducing autoantibody levels and improving symptoms. 2) Plasmapheresis, which helps remove pathogenic antibodies from the bloodstream. 3) Emerging treatments like stem cell therapies, which are being explored for their potential to modulate the immune system and promote neuromuscular repair. 4) Newer immunosuppressive agents and biologics targeting specific immune pathways involved in MG.

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CAR T-cell Therapy

MuSK-CAART for Myasthenia Gravis

Phase 1

Recruiting

Research Sponsored by Cabaletta Bio

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Positive anti-MuSK antibody test at screening

Confirmed diagnosis of MuSK-type MG with at least 1 prior positive anti-MuSK antibody test

Must not have

Rituximab in the last 12 months

Prednisone > 0.25mg/kg/day [in Part A]

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 36 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new cell therapy called MuSK-CAART for patients with a severe muscle disease known as MuSK myasthenia gravis. These patients have harmful antibodies that attack their muscles. The therapy uses special cells to find and stop these bad antibodies, potentially leading to long-term relief from the disease. Rituximab has been used to treat MuSK myasthenia gravis, showing some success in patients who are refractory to standard treatments.

Who is the study for?

This trial is for people with MuSK myasthenia gravis, a muscle weakness disease. Participants must have tested positive for anti-MuSK antibodies and negative for anti-AChR antibodies, with an MG severity Class I to IVa. They can't join if they're on high-dose prednisone, had other autoimmune treatments recently, received investigational MG treatments in the last 12 weeks or rituximab in the past year.

What is being tested?

The study tests different doses of MuSK-CAART alone or combined with cyclophosphamide (CY) and fludarabine (FLU). It's an open-label phase 1 trial aiming to see if this cell therapy can cause remission in patients with active MuSK myasthenia gravis.

What are the potential side effects?

Potential side effects may include immune system reactions due to cell therapy, as well as typical chemotherapy-related issues like nausea, fatigue, hair loss from CY and FLU. The exact side effects of MuSK-CAART are being studied.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I tested positive for anti-MuSK antibodies.

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I have been diagnosed with MuSK myasthenia gravis and tested positive for anti-MuSK antibodies.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not received Rituximab in the last 12 months.

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I am taking more than a small dose of prednisone daily.

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I am on immunosuppressive therapy for an autoimmune disorder.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 36 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 36 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 36 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Adverse events

Secondary study objectives

Cells

Body Weight Changes

Percent of CAAR-transduced cells

+1 more

Other study objectives

Measurement of Clinical Symptoms using MG-ADL

Measurement of Clinical Symptoms using MGC

Measurement of Clinical Symptoms using QMG

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: MuSK-CAARTExperimental Treatment1 Intervention

Cohort A: Infusion of MuSK-CAART at various dose levels with or without pre-treatment (6 groups planned). Cohort B: Infusion of MuSK-CAART at the dose regimen selected from Part A.

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Myasthenia Gravis (MG) include acetylcholinesterase inhibitors, immunosuppressants, and plasmapheresis. Acetylcholinesterase inhibitors increase the availability of acetylcholine at the neuromuscular junction, improving muscle contraction. Immunosuppressants reduce the immune system's attack on acetylcholine receptors. Plasmapheresis removes circulating autoantibodies from the blood. MuSK-CAART, a cell therapy under investigation, targets and eliminates pathogenic autoantibodies against the MuSK protein, potentially leading to durable remission. These treatments are crucial as they address the underlying autoimmune response, providing symptom relief and improving quality of life for MG patients.

Immunotherapy in neuromuscular disorders: current and future strategies.Immunotherapy for Management of Thymic Epithelial Tumors: A Double-Edged Sword.Advances in Immunotherapies for Gliomas.