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

Официальное название

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

Обзор

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.

Подробное описание

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 (gMG). 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).

Вмешательства

• Генная терапия YTB323
  CAR-T cell suspension for intravenous infusion

Первичные конечные точки

• Occurrence, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Baseline up to 2 years]

Вторичные конечные точки (12)

• Plasma Pharmacokinetics (PK) of YTB323 - CMAX [Срок оценки: Pre-dose Day 1 up to 2 years]
• Plasma Pharmacokinetics (PK) of YTB323 - AUC [Срок оценки: Pre-dose Day 1 up to 2 years]
• Plasma Pharmacokinetics (PK) of YTB323 - Tmax [Срок оценки: Pre-dose Day 1 up to 2 years]
• Plasma Pharmacokinetics (PK) of YTB323 - Clast [Срок оценки: Pre-dose Day 1 up to 2 years]
• Plasma Pharmacokinetics (PK) of YTB323 - Tlast [Срок оценки: Pre-dose Day 1 up to 2 years]
• Cellular immunogenicity of YTB323 [Срок оценки: Pre-dose lymphodepletion up to 2 years]
• Humoral immunogenicity of YTB323 [Срок оценки: Pre-dose lymphodepletion up to 2 years]
• Neutralizing immunogenicity of YTB323 [Срок оценки: Pre-dose lymphodepletion up to 2 years]
• Change from Baseline of MG-ADL score [Срок оценки: Baseline up to 2 years]
• Change from Baseline of QMG total score [Срок оценки: Baseline up to 2 years]
• Proportion of patients with a ≥3-point reduction of QMG total score sustained for 6 months post Baseline [Срок оценки: Baseline up to 2 years]
• Proportion of patients with a ≥2-point reduction of MG-ADL score sustained for 6 months post Baseline [Срок оценки: Baseline up to 2 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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).

Other protocol-defined inclusion/exclusion criteria may apply

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Univ Cali Irvine ALS Neuromuscular — Orange
• Wake Forest Univ School of Medicine — Winston-Salem
• Thomas Jefferson University — Philadelphia
• Houston Methodist Hospital — Houston

Франция · 3 центра

• Novartis Investigative Site — Bordeaux
• Novartis Investigative Site — Brest
• Novartis Investigative Site — Lille

Япония · 2 центра

• Novartis Investigative Site — Chiba
• Novartis Investigative Site — Kyoto

Великобритания · 2 центра

• Novartis Investigative Site — Sheffield
• Novartis Investigative Site — London

Идентификаторы

NCT: NCT06704269 · CYTB323O12101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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