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

Official title

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

Overview

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.

Interventions

• Genetic BMS-986515
  Specified dose on specified days
• Drug Fludarabine
  Specified dose on specified days
• Drug Cyclophosphamide
  Specified dose on specified days
• Drug Tocilizumab
  Specified dose on specified days

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

\- 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.

Exclusion criteria

\- 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 5 centers

• 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

Poland · 4 centers

• 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

Australia · 3 centers

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

Brazil · 3 centers

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

Spain · 3 centers

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

United States · 2 centers

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

Czechia · 2 centers

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

France · 2 centers

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

Israel · 2 centers

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

Romania · 2 centers

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

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗