YTB323: CAR-T cell suspension for intravenous infusion
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
Sex
ALL
Min age
18 Years
Max age
65 Years
Healthy volunteers
No
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
Primary outcome measure(s)
Occurrence, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) — Baseline up to 2 years Incidence of AE's, including Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANs), changes in Vital Signs, Laboratory parameters, ECG, and neurological status qualifying and reported as AEs.
Trial sites (11)
Facility
City
Region
Status
Univ Cali Irvine ALS Neuromuscular
Orange
California
Wake Forest Univ School of Medicine
Winston-Salem
North Carolina
Thomas Jefferson University
Philadelphia
Pennsylvania
Houston Methodist Hospital
Houston
Texas
Novartis Investigative Site
Bordeaux
France
Novartis Investigative Site
Brest
France
Novartis Investigative Site
Lille
France
Novartis Investigative Site
Chiba
Chiba
Novartis Investigative Site
Kyoto
Japan
Novartis Investigative Site
Sheffield
South Yorkshire
Novartis Investigative Site
London
United Kingdom
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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