A Study of Healthy Donor CD19-targeted Allogeneic CAR T Cells in Participants With Severe, Refractory Autoimmune Diseases

Официальное название

A Phase 1, Multicenter, Open-label Study of BMS-986515, Healthy Donor Allogeneic CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, in Participants With Severe, Refractory Autoimmune Diseases

Обзор

The purpose of this study is to determine the safety, tolerability, optimal dose, and preliminary efficacy of BMS-986515, a healthy donor (HD) allogeneic CD19-targeted CART cell product, in participants with severe, refractory autoimmune diseases.

Вмешательства

• Генная терапия BMS-986515
  Specified dose on specified days
• Препарат Fludarabine
  Specified dose on specified days
• Препарат Cyclophosphamide
  Specified dose on specified days
• Препарат Tocilizumab
  Specified dose on specified days

Первичные конечные точки

• Number of participants with treatment-emergent adverse events (TEAEs) [Срок оценки: Up to 24 months post BMS-986515 infusion]
• Number of participants with serious AEs (SAEs) [Срок оценки: Up to 24 months post BMS-986515 infusion]
• Number of participants with AEs of special interest (AESIs) [Срок оценки: Up to 24 months post BMS-986515 infusion]
• Number of participants with laboratory abnormalities [Срок оценки: Up to 24 months post BMS-986515 infusion]
• Number of participants with Dose-Limiting Toxicities (DLTs) [Срок оценки: Up to 24 months post BMS-986515 infusion]
• Number of participants with DLTs that occur during the DLT evaluation period [Срок оценки: 28 days post-BMS-986515 infusion]

Вторичные конечные точки (12)

• Maximum observed concentration (Cmax) [Срок оценки: Up to 2 years]
• Area under the concentration-time curve (AUC) [Срок оценки: Up to 2 years]
• Time of maximum observed concentration (Tmax) [Срок оценки: Up to 2 years]
• Number of participants with interstitial lung disease (ILD) with no worsening of pulmonary function from baseline to Week 24 [Срок оценки: Up to 2 years]
• Number of participants with a humoral immune response (anti-therapeutic antibodies) against BMS-986515 [Срок оценки: Up to 2 years]
• Number of participants who achieve definition of remission in systemic lupus erythematosus (DORIS) remission at Week 24 [Срок оценки: Up to Week 24]
• Number of participants who achieve Lupus Low Disease Activity State (LLDAS) at Week 24 [Срок оценки: Up to Week 24]
• Change in proteinuria measured by urine protein creatinine ratio (UPCR) from baseline to Week 24 [Срок оценки: Up to Week 24]
• Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) from baseline to Week 24 [Срок оценки: Up to Week 24]
• Number of participants who achieve Myositis Response Criteria Total Improvement Score (MRC TIS) at Week 24 [Срок оценки: Up to Week 24]
• Change in International Myositis Outcome Assessment Collaborative Study Group (IMACS) outcome measure set for disease activity at week 24 from baseline [Срок оценки: Up to Week 24]
• Change in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) at week 24 from baseline [Срок оценки: Up to Week 24]

Критерии участия

Критерии включения

\- Systemic lupus erythematosus (SLE) population:.

i) Diagnosis of SLE based on the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR).

ii) Participant must be positive for at least one of the following antibodies at screening: anti-nuclear antibody, anti-dsDNA, anti-histone, anti-chromatin or anti-Sm antibody.

iii) Inadequate response or intolerance to steroids and immunosuppressive therapies.

iv) Participants must have active disease at screening.

\- Inflammatory myopathy (IIM) population:.

i) Participants meeting the 2017 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria.

ii) Participants must meet criteria for with severe, refractory IIM. iii) Participants who had inadequate response to steroids and prior immunosuppressive therapies.

iv) Evidence of active disease.

\- Systemic sclerosis (SSc) population:.

i) Participant must fulfill the 2013 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis.

ii) Inadequate disease response or intolerance to prior therapies. iii) Participants diagnosed with progressive systemic sclerosis including skin disease and/or interstitial lung disease.

\- Rheumatoid arthritis (RA) population:.

i) Participants with difficult to treat RA. ii) Participants with a diagnosis of RA meeting 2010 ACR/EULAR criteria. iii) Rheumatoid arthritis disease activity at screening and baseline visit. iv) Inadequate disease response or intolerance to standard of care therapy.

Критерии исключения

\- All participants:.

i) Any other systemic autoimmune disease. ii) Pregnant or nursing women. iii) Active hepatitis B, C or HIV. iv) Prior history of malignancies. v) Uncontrolled or active infection. vi) History of certain cardiovascular conditions within 6 months prior to screening.

vii) Previous CAR-T cell therapy. viii) Significant lung impairment. ix) Inadequate organ function. x) Active, clinically significant, central nervous system (CNS) disorders.

• SLE population:.

i) Participants who have SLE because of drugs or have other autoimmune diseases along with SLE.

• IIM population:.

i) Participants who have other forms of myopathies other than IIM. ii) Severe muscle damage.

• SSc population:.

i) People who have high blood pressure in the arteries of the lungs caused by SSc, which needs regular treatment to keep it under control.

ii) Rapidly deteriorating SSc, or history of severe kidney disease.

• RA population:.

i) People who have additional autoimmune diseases along with RA.

• Other protocol-defined inclusion/exclusion criteria 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

Германия · 5 центров

• Universitaetsklinikum Duesseldorf — Düsseldorf
• Universitaetsklinikum Schleswig-Holstein Campus Kiel — Kiel
• Charité - Universitaetsmedizin Berlin - Campus Bejnamin Franklin — Berlin
• Universitätsklinikum Carl Gustav Carus an der TU Dresden — Dresden
• Local Institution - 0031 — Hamburg

Польша · 4 центра

• Uniwersyteckie Centrum Kliniczne — Gdansk
• Szpital Specjalistyczny nr 1 w Bytomiu — Bytom
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy w Gli — Gliwice
• Local Institution - 0017 — Lodz

Австралия · 3 центра

• Local Institution - 0007 — Camperdown
• Local Institution - 0008 — Brisbane
• Local Institution - 0013 — Clayton

Бразилия · 3 центра

• Local Institution - 0040 — Salvador
• Local Institution - 0039 — Porto Alegre
• Local Institution - 0038 — São Paulo

Испания · 3 центра

• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital de la Santa Creu i Sant Pau — Barcelona
• Hospital Universitario Ramón y Cajal — Madrid

США · 2 центра

• Brigham And Womens Hospital — Boston
• Duke University — Durham

Чехия · 2 центра

• Local Institution - 0004 — Prague
• Revmatologicky ustav — Prague

Франция · 2 центра

• CHU Strasbourg-Hautepierre — Strasbourg
• Hopital Claude Huriez - CHU de Lille — Lille

Израиль · 2 центра

• Sheba Medical Center — Ramat Gan
• Hadassah Medical Center — Jerusalem

Румыния · 2 центра

• ARENSIA Exploratory Medicine — Cluj-Napoca
• Fundeni Clinical Institute — Bucharest

Идентификаторы

NCT: NCT07115745 · IM060-0001 · 2024-517681-41 · U1111-1308-9273

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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