A Study to Assess the Safety and Clinical Activity of Azer-cel in Participants With B-cell Mediated Autoimmune Disorders

Официальное название

A Phase 1, Open-label Study to Evaluate the Safety and Clinical Activity of Azercabtagene Zapreleucel in Participants With B-cell Mediated Autoimmune Disorders

Обзор

The main objective of the study is to determine the recommended phase 2 dose (RP2D) of Azercabtagene zapreleucel (azer-cel).

Вмешательства

• Препарат Azercabtagene zapreleucel (azer-cel)
  IV infusion

Первичные конечные точки

• Number of Participants with Dose-Limiting Toxicities (DLTs) [Срок оценки: From Day 0 to Day 28]

Вторичные конечные точки (12)

• Number of Participants with Treatment Emergent Adverse Events (TEAEs), Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) [Срок оценки: Up to Day 720]
• Change From Baseline in CAR T-cell Toxicities [Срок оценки: Baseline, up to Day 720]
• Pharmacokinetics (PK) Plasma Concentrations of Azer-cel [Срок оценки: Up to Day 720]
• Pharmacodynamics (PD) Plasma Concentrations of Azer-cel [Срок оценки: Up to Day 720]
• Time to Confirmed Disability Progression (CDP) [Срок оценки: Up to Day 720]
• Time to Confirmed Disability Improvement (CDI) [Срок оценки: Up to Day 720]
• Change From Baseline in Brain MRI Gadolinium Enhancing T1, New or Enlarging Hyperintense T2 [Срок оценки: Baseline, up to Day 720]
• Change From Baseline in Whole Brain Atrophy [Срок оценки: Baseline, up to Day 720]
• Change From Baseline in Modified Rankin Scale (mRS) [Срок оценки: Baseline, up to Day 720]
• Change From Baseline in Visual Acuity on Landolt C Broken Ring Chart (Low Contrast Visual Acuity [LCVA]) and High Contrast Visual Acuity (HCVA) [Срок оценки: Baseline, up to Day 720]
• Change from Baseline in Myasthenia Gravis Activities of Daily Living Profile (MG-ADL) Total Score [Срок оценки: Baseline, up to Day 720]
• Change from Baseline in the Revised 15-Component Myasthenia Gravis Quality of Life (MG-QOL15r) [Срок оценки: Baseline, up to Day 720]

Критерии участия

Критерии включения

PMS and RMS inclusion criteria:

• Age 18 years to ≤60 years (inclusive) at screening.
• Expanded Disability Status Scale (EDSS) score 3.0 - 6.5 (inclusive) at screening.
• Diagnosis of primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (non-active or active), or Relapsing MS (RMS).
• Documented evidence of disability progression independent of relapse (PIRA) at any point over the 12 months prior to the screening visit.

NMOSD inclusion criteria:

• Between age 18 and 65 years, inclusive at the time of signing the informed consent.
• EDSS score between 2.0 and 7.0 at screening, inclusive (for higher EDSS, the Investigator must assess that the participant is reasonably able to participate in the study).
• Diagnosis of anti-aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive at screening (verified by the allocated central laboratory) and Neuromyelitis Optica Spectrum Disorder (NMOSD).
• Must meet the appropriate NMOSD treatment washout criteria prior to receiving lymphodepletion.

MG Inclusion criteria:

• Age ≥18 and ≤70 years of age at the time of signing the informed consent.
• Diagnosed with gMG at least 1 year prior to the date of signing the informed consent.
• Confirmation of MG Diagnosis:

• Positive serologic test for anti-acetylcholine receptor (AChR) antibodies or anti-muscle-specific kinase (MuSK) antibodies confirmed at screening AND
• One of the following (either historical or during screening):

• Abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation.
• Positive anticholinesterase test (e.g., edrophonium chloride test).
• Demonstrated improvement in MG signs on oral cholinesterase inhibitors, as assessed by the treating physician.
• MG activities of daily living (MG-ADL) score ≥6 at screening.

CIDP Inclusion criteria

• Age ≥18 and ≤70 years of age at the time of signing the informed consent.
• Participant must have either typical CIDP, or one of the following two CIDP variants: motor CIDP, multifocal CIDP (also known as Lewis Sumner Syndrome).
• CIDP Disease Activity Status (CDAS): CDAS score ≥3 at screening.
• INCAT Disability Score: INCAT disability score ≥4 to ≤9 score at screening.

General Exclusion Criteria:

• History of malignancy that has not been in remission for at least 2 years.
• Viral Screening

• Evidence of chronic active or history of hepatitis B virus (HBV).
• Seropositive for human immunodeficiency virus (HIV) antibody.
• History of bone marrow/hematopoietic stem cell or solid organ transplantation.
• Prior treatment with adoptive T-cell therapy or any gene therapy product directed at any target (e.g. CAR T-cell therapy).

Note: Other protocol-specified 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

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• TG Therapeutics Investigational Trial Site — La Jolla
• TG Therapeutics Investigational Trial Site — Ann Arbor
• TG Therapeutics Investigational Trial Site — Omaha
• TG Therapeutics Investigational Trial Site — New York
• TG Therapeutics Investigational Trial Site — Rochester
• TG Therapeutics Investigational Trial Site — Cleveland
• TG Therapeutics Investigational Trial Site — Columbus
• TG Therapeutics Investigational Trial Site — Milwaukee

Идентификаторы

NCT: NCT06680037 · TG-Azercel-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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