Assessing YTB323 for treatment-resistant generalized myasthenia gravis

An Open-label, Multi-center, Phase I/II Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Participants With Treatment-resistant Generalized Myasthenia Gravis

This study is testing a new CAR-T cell therapy called YTB323 to see if it can help people with treatment-resistant generalized myasthenia gravis who haven't found relief with other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Drugs / interventions: CAR-T
• Locations: 10 sites (Orange, California and 9 other locations)
• Trial ID: NCT06704269 on ClinicalTrials.gov

What this trial studies

This phase I/II study evaluates the safety, efficacy, and cellular kinetics of YTB323, a CAR-T cell therapy, in patients with treatment-resistant generalized myasthenia gravis (gMG). The open-label, multi-center trial aims to enroll approximately 15 participants, starting with a sentinel cohort of 3 patients followed by an expansion cohort of 12. Participants will be monitored for up to 15 years post-treatment to assess long-term outcomes and safety. The study focuses on patients who have not responded adequately to existing treatments.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with treatment-resistant generalized myasthenia gravis who have a significant MG-ADL score despite previous treatments.

Not a fit: Patients with mild or non-treatment-resistant forms of generalized myasthenia gravis may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with treatment-resistant generalized myasthenia gravis.

How similar studies have performed: While CAR-T therapies have shown promise in other conditions, this specific application in generalized myasthenia gravis is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Confirmed gMG diagnosis supported by the following:

   * Documented report of positive serology testing for either AChR antibodies or MuSK antibodies at screening AND at least one of the following:
   * History of abnormal neuromuscular transmission test demonstrated by repetitive nerve stimulation or single-fiber electromyography
   * History of positive acetylcholinesterase inhibitor test
   * Improvement in MG signs on an oral acetylcholinesterase inhibitor as assessed by the treating physician
2. MGFA Class III-IVa (gMG) at screening
3. Treatment-resistant gMG as defined by: MG-ADL score ≥ 6 (≥50% non-ocular) at screening despite adequate treatment trials with at least two different non-steroidal immunosuppressive drugs given at adequate doses and duration of therapy.
4. If on chronic corticosteroids, must be on a stable dose of corticosteroids for ≥1 month prior to screening and have the ability and willingness to taper to a maximum dose of 10 mg prednisolone daily or equivalent at least one week before leukapheresis
5. If treated with cholinesterase inhibitors, patients must be on a stable dose for at least two weeks prior to screening

Exclusion Criteria:

1. Exclusively ocular myasthenia gravis (MGFA I), mild symptoms (MGFA II), or severe bulbar disease or MG crisis, MGFA Class IVb or V at screening
2. History of bone marrow/hematopoietic stem cell or solid organ transplantation.
3. Clinically significant active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C) confirmed by clinical evidence, imaging, or positive laboratory tests one month prior to leukapheresis
4. Other uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids, at screening
5. Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody, at screening
6. Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy).

Other protocol-defined inclusion/exclusion criteria may apply

Where this trial is running

Orange, California and 9 other locations

• Univ Cali Irvine ALS Neuromuscular — Orange, California, United States (Recruiting)
• Wake Forest Univ School of Medicine — Winston-Salem, North Carolina, United States (Recruiting)
• Houston Methodist Hospital — Houston, Texas, United States (Recruiting)
• Novartis Investigative Site — Bordeaux, France (Recruiting)
• Novartis Investigative Site — Brest, France (Recruiting)
• Novartis Investigative Site — Lille, France (Recruiting)
• Novartis Investigative Site — Chiba, Japan (Recruiting)
• Novartis Investigative Site — Kyoto, Japan (Recruiting)
• Novartis Investigative Site — Sheffield, South Yorkshire, United Kingdom (Recruiting)
• Novartis Investigative Site — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Generalized Myasthenia Gravis; myasthenia gravis; generalized myasthenia gravis; YTB323; CAR-T