Refractory Autoimmune Diseases
Conditions
Keywords
CAR-T, Cell Therapy, Autoimmune disease, Systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, rheumatoid arthritis, Musculoskeletal Diseases, Myositis, Lupus Erythematosus, Systemic, Scleroderma, Systemic, Scleroderma, Diffuse, Autoimmune Diseases, Sclerosis, Skin Diseases, Connective tissue diseases, BMS-986515, Allogeneic CAR T, CD19 Allogeneic CAR T, AlloCAR T, Cell Therapy, CAR T, SLE, Lupus Nephritis, SSc, IIM, Polymyositis, Dermatomyositis, RA
Brief summary
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
GENETICBMS-986515
Specified dose on specified days
DRUGFludarabine
Specified dose on specified days
DRUGCyclophosphamide
Specified dose on specified days
DRUGTocilizumab
Specified dose on specified days
Sponsors
Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-emergent adverse events (TEAEs) | Up to 24 months post BMS-986515 infusion | All participants |
| Number of participants with serious AEs (SAEs) | Up to 24 months post BMS-986515 infusion | All participants |
| Number of participants with AEs of special interest (AESIs) | Up to 24 months post BMS-986515 infusion | All participants |
| Number of participants with laboratory abnormalities | Up to 24 months post BMS-986515 infusion | All participants |
| Number of participants with Dose-Limiting Toxicities (DLTs) | Up to 24 months post BMS-986515 infusion | All participants |
| Number of participants with DLTs that occur during the DLT evaluation period | 28 days post-BMS-986515 infusion | All participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed concentration (Cmax) | Up to 2 years | All participants |
| Area under the concentration-time curve (AUC) | Up to 2 years | All participants |
| Time of maximum observed concentration (Tmax) | Up to 2 years | All participants |
| Number of participants with interstitial lung disease (ILD) with no worsening of pulmonary function from baseline to Week 24 | Up to 2 years | All participants |
| Number of participants with a humoral immune response (anti-therapeutic antibodies) against BMS-986515 | Up to 2 years | All participants |
| Number of participants who achieve definition of remission in systemic lupus erythematosus (DORIS) remission at Week 24 | Up to Week 24 | Systemic lupus erythematosus (SLE) participants |
| Number of participants who achieve Lupus Low Disease Activity State (LLDAS) at Week 24 | Up to Week 24 | SLE participants |
| Change in proteinuria measured by urine protein creatinine ratio (UPCR) from baseline to Week 24 | Up to Week 24 | SLE participants |
| Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) from baseline to Week 24 | Up to Week 24 | SLE, systemic sclerosis (SSc), and rheumatoid arthritis (RA) participants |
| Number of participants who achieve Myositis Response Criteria Total Improvement Score (MRC TIS) at Week 24 | Up to Week 24 | Inflammatory myopathy (IIM) participants |
| Change in International Myositis Outcome Assessment Collaborative Study Group (IMACS) outcome measure set for disease activity at week 24 from baseline | Up to Week 24 | IIM participants |
| Change in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) at week 24 from baseline | Up to Week 24 | Dermatomyositis (DM) participants only |
| Number of participants who achieve an minimal clinically important differences in SSc (MCID) from baseline of the modified Rodnan Skin Score (mRSS) at Week 24 | Up to Week 24 | SSc participants |
| Change from baseline of the Revised Composite Response Index in Systemic Sclerosis (CRISS) at Week 24 | Up to Week 24 | SSc participants |
| Number of participants with low disease activity at Week 24 from baseline | Up to Week 24 | RA participants |
Countries
Australia, Brazil, Czechia, France, Germany, Israel, Poland, Romania, Spain, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed