Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Generalized Myasthenia Gravis

Last updated: March 14, 2025
Sponsor: Novartis Pharmaceuticals
Overall Status: Active - Recruiting

Phase

1/2

Condition

Neuropathy

Polymyositis (Inflammatory Muscle Disease)

Sarcopenia

Treatment

YTB323

Clinical Study ID

NCT06704269
CYTB323O12101
  • Ages 18-65
  • All Genders

Study Summary

This is a phase I/II study to assess safety, efficacy, and cellular kinetics of YTB323 in participants with treatment-resistant generalized myasthenia gravis. YTB323 is a Biological CAR-T cell therapy.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Confirmed gMG diagnosis supported by the following:
  • Documented report of positive serology testing for either AChR antibodies orMuSK antibodies at screening AND at least one of the following:

  • History of abnormal neuromuscular transmission test demonstrated by repetitivenerve stimulation or single-fiber electromyography

  • History of positive acetylcholinesterase inhibitor test

  • Improvement in MG signs on an oral acetylcholinesterase inhibitor as assessedby the treating physician

  1. MGFA Class III-IVa (gMG) at screening

  2. Treatment-resistant gMG as defined by: MG-ADL score ≥ 6 at screening despiteadequate treatment trials with at least two different non-steroidalimmunosuppressive drugs given at adequate doses and duration of therapy.

  3. If on chronic corticosteroids, the ability and willingness to taper to a maximumdose of 10 mg prednisolone daily or equivalent at least one week beforeleukapheresis

  4. If treated with cholinesterase inhibitors, patients must be on a stable dose for atleast two weeks prior to screening

Exclusion

Exclusion Criteria:

  1. Exclusively ocular myasthenia gravis (MGFA I), mild symptoms (MGFA II), or severebulbar 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, atscreening

  5. Participants with a known immunodeficiency syndrome (AIDS, hereditary immunedeficiency, drug induced immune deficiency), or tested positive for HIV antibody, atscreening

  6. Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior genetherapy product (e.g. CAR-T cell therapy).

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Total Participants: 15
Treatment Group(s): 1
Primary Treatment: YTB323
Phase: 1/2
Study Start date:
March 31, 2025
Estimated Completion Date:
August 02, 2029

Study Description

This is an open-label, multi-center, non-confirmatory study intended to assess safety, efficacy, and cellular kinetics of YTB323 treatment in participants with treatment-resistant generalized myasthenia gravis in order to enable a benefit to risk assessment for further development in generalized myasthenia gravis (gMS). The study plans to enroll approximately 15 participants with treatment-resistant gMG. The study utilizes a single dose design across 2 cohorts, consisting of a sentinel cohort of 3 patients followed by an expansion cohort of an additional 12 patients.

All participants dosed with YTB323 will be followed until 15 years after YTB323 administration in the Long-Term Follow-up (LTFU).

Connect with a study center

  • Novartis Investigative Site

    Chiba, 2608677
    Japan

    Active - Recruiting

  • Novartis Investigative Site

    Kyoto, 606 8507
    Japan

    Active - Recruiting

  • Univ Cali Irvine ALS Neuromuscular

    Orange, California 92868
    United States

    Active - Recruiting

  • Houston Methodist Hospital

    Houston, Texas 77030
    United States

    Active - Recruiting

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