A Study of AZD0120 in Autoimmune Diseases

Официальное название

A Phase 1b, Open-label, Multi-cohort Study of AZD0120, an Autologous CD19/BCMA Targeting Chimeric Antigen Receptor T-cell, in Adults With Autoimmune Diseases

Обзор

This trial is a Phase 1b, open-label, multi-center, clinical study of AZD0120, a BCMA/CD19 dual targeting CAR+ T-cell therapy, to evaluate the safety and tolerability in adult participants with systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), or difficult-to-treat rheumatoid arthritis (D2T RA).

Подробное описание

This is a Phase 1b, open-label, multi-center, multi-cohort clinical study of AZD0120, a CD19/BCMA dual CAR T-cell therapy, to evaluate the safety in adult participants with systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), or difficult-to-treat rheumatoid arthritis (D2T RA) for determination of the recommended phase 2 dose for each disease cohort. Approximately 9-12 participants will be evaluated per disease cohort.

Вмешательства

• Биопрепарат AZD0120
  CD19/BCMA Autologous CAR T-cell therapy product

Первичные конечные точки

• Number of participants and severity of dose limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs) [Срок оценки: 1 year]

Вторичные конечные точки (12)

• Cellular Kinetics - Cmax [Срок оценки: 1 year]
• Cellular Kinetics - Tmax [Срок оценки: 1 year]
• Cellular Kinetics - AUC [Срок оценки: 1 year]
• Cellular Kinetics - t½λz [Срок оценки: 1 year]
• Cellular Kinetics - Clast [Срок оценки: 1 year]
• Cellular Kinetics - Tlast [Срок оценки: 1 year]
• Cellular Kinetics - AUClast [Срок оценки: 1 year]
• Anti-drug antibodies (ADA) developed against AZD0120 from baseline [Срок оценки: 1 year]
• Proportion of participants with detectable replication competent lentivirus (RCL) at pre-specified post infusion timepoints. [Срок оценки: 1 year]
• Change from baseline in the Disease Activity Score (DAS) 28-C-reactive protein (CRP). The DAS28-CRP is a measure from 0-10 with higher scores indicating greater disease activity. [Срок оценки: 1 year]
• Change from baseline in modified Rodnan Skin Score (mRSS). The mRSS is a measure of skin thickness with a range of 0-51 with higher scores indicating more severe disease. [Срок оценки: 1 year]
• Change from baseline in the total improvement score (TIS). The TIS ranges from 0-100 with higher scores indicating greater improvement. [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Capable of giving signed informed consent.
• Adequate physiological function and reserve at screening.
• Able to comply with recommended medication washout period.
• Participants who are suitable for the study as determined by medical evaluation and at the discretion of the investigator.
• Willingness to remain on/start appropriate, highly effective methods of birth control or other acceptable criteria.

Критерии исключения

• BMI at screening < 18 or > 35kg/m2.
• Any prior CAR T exposure.
• Unable or unwilling to remain within proximity (\~2 hours travel time) of the administering investigational site for the first 28 days post study drug administration.
• Received a bone marrow or solid organ transplant at any time or on an active transplant waiting list.
• Received any investigational drug within ≥ 5 half-lives or 4 weeks, whichever is longer, prior to screening.
• Has certain heart conditions that could make it unsafe or unsuitable to take part in the study.
• Requirement for supplemental oxygen at rest (except at night for sleep apnea) or mechanical ventilation.
• Uncontrolled hypertension (> 160/100 mmHg) or symptomatic hypertension.
• Any central nervous system disease that may impact participants safety in the investigator's opinion.
• Other concurrent autoimmune or autoinflammatory disease. Certain autoimmune/autoinflammatory diseases may be included after discussion with the medical monitor.
• Evidence of clinically significant bleeding or active bleeding conditions within 90 days before screening
• History of malignancy or ongoing treatment for prior malignancy. Certain malignancies may be excepted.
• Known genetic inborn error of immunity and/or primary immunodeficiency.
• Active viral, bacterial, or fungal infection, or any ongoing infection that requires systemic antimicrobial therapy in the 4 weeks prior to screening.
• Seropositive for HIV.
• Active viral hepatitis are excluded.
• Active syphilis, positive for Treponema pallidum antibody.
• Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis or lymphodepletion.
• Not up-to-date on vaccinations per local/national health authority or institutional guidelines for immune-compromised individuals.
• Known life threatening allergies, hypersensitivity, or intolerance to AZD0120 or its excipients, including dimethyl sulfoxide.
• Contraindications or hypersensitivity to fludarabine and cyclophosphamide.
• Major surgery, or has surgery planned during the study.
• Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 1 year after receiving study treatment (whichever is later).
• Plans to father a child while enrolled in this study or within 1 year after receiving study treatment (whichever is later).
• Any issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to provide informed consent or any condition in the opinion of the investigator, participation would not be in the best interest of the participant.

Other protocol-defined eligibility 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

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• Research Site — Tucson
• Research Site — Stanford
• Research Site — Chicago
• Research Site — Ann Arbor
• Research Site — St Louis
• Research Site — New York
• Research Site — Chapel Hill
• Research Site — Seattle

Германия · 6 центров

• Research Site — Berlin
• Research Site — Erlangen
• Research Site — Hamburg
• Research Site — Jena
• Research Site — Mainz
• Research Site — Würzburg

Испания · 3 центра

• Research Site — Barcelona
• Research Site — Madrid
• Research Site — Madrid

Австралия · 2 центра

• Research Site — Darlinghurst
• Research Site — Waratah

Великобритания · 2 центра

• Research Site — Edinburgh
• Research Site — London

Швеция · 1 центр

• Research Site — Huddinge

Идентификаторы

NCT: NCT07295847 · D8318C00001 · 29707

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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