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

NCT06704269 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CYTB323O12101
• Study Type: interventional
• Target: 15
• Locations: 4 countries
• Sites: 10

Brief 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.

Conditions

Generalized Myasthenia Gravis

Keywords

myasthenia gravis; generalized myasthenia gravis; YTB323; CAR-T

Outcome Measures

Primary Outcomes (1)

• Occurrence, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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.

  Baseline up to 2 years

Secondary Outcomes (13)

• Plasma Pharmacokinetics (PK) of YTB323 - CMAX

  Pre-dose Day 1 up to 2 years

• Plasma Pharmacokinetics (PK) of YTB323 - AUC

  Pre-dose Day 1 up to 2 years

• Plasma Pharmacokinetics (PK) of YTB323 - Tmax

  Pre-dose Day 1 up to 2 years

• Plasma Pharmacokinetics (PK) of YTB323 - Clast

  Pre-dose Day 1 up to 2 years

• Plasma Pharmacokinetics (PK) of YTB323 - Tlast

  Pre-dose Day 1 up to 2 years

Study Arms (1)

YTB323

EXPERIMENTAL

YTB323 single intravenous (i.v.) infusion

Genetic: YTB323

Interventions

YTB323 GENETIC

CAR-T cell suspension for intravenous infusion

YTB323

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• MGFA Class III-IVa (gMG) at screening
• 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.
• 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
• If treated with cholinesterase inhibitors, patients must be on a stable dose for at least two weeks prior to screening

You may not qualify if:

• Exclusively ocular myasthenia gravis (MGFA I), mild symptoms (MGFA II), or severe bulbar disease or MG crisis, MGFA Class IVb or V at screening
• History of bone marrow/hematopoietic stem cell or solid organ transplantation.
• 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
• Other uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids, at screening
• Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody, at screening
• Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Univ Cali Irvine ALS Neuromuscular

Orange, California, 92868, United States

RECRUITING

Wake Forest Univ School of Medicine

Winston-Salem, North Carolina, 27157-1052, United States

RECRUITING

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Novartis Investigative Site

Bordeaux, 33076, France

RECRUITING

Novartis Investigative Site

Brest, 29200, France

RECRUITING

Novartis Investigative Site

Lille, 59037, France

RECRUITING

Novartis Investigative Site

Chiba, 260 8677, Japan

RECRUITING

Novartis Investigative Site

Kyoto, 6068507, Japan

RECRUITING

Novartis Investigative Site

Sheffield, South Yorkshire, S10 2JF, United Kingdom

RECRUITING

Novartis Investigative Site

London, SE5 9RS, United Kingdom

RECRUITING

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2024
• First Posted: November 26, 2024
• Study Start: April 22, 2025
• Primary Completion (Estimated): October 26, 2029
• Study Completion (Estimated): October 26, 2029
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

JP (2); US (3); FR (3); GB (2)