A Study of CC-97540 in Participants With Severe, Refractory Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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The purpose of this study is to establish the tolerability, preliminary efficacy, and pharmacokinetics of CC-97540 in participants with severe, refractory Systemic Lupus Erythematosus (SLE).

Official Title
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A Phase 1, Multicenter, Open-Label Study Of CC-97540 (BMS-986353), CD19-Targeted Nex-T Chimeric Antigen Receptor (CAR) T Cells, in Participants With Severe, Refractory Systemic Lupus Erythematosus (SLE)

Conditions
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Lupus Erythematosus, Systemic

Intervention / Treatment
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* Drug: CC-97540
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of SLE defined as follows: Fulfilling the 2019 ACR/EULAR classification criteria of SLE Presence of anti-dsDNA, anti-histone, anti-chromatin, or anti-Sm antibodies SLE disease activity Active disease at screening, defined as ≥ 1 major organ system with a BILAG A score (excluding musculoskeletal, mucocutaneous, and/or constitutional organ system) ii) Inadequate response to glucocorticoids and to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, obinutuzumab, cyclosporin, tacrolimus or voclosporin. i) Insufficient response is defined as lack of response, insufficient response or lack of sustained response to appropriate doses. Intolerance is not considered insufficient response ii) Methotrexate and azathioprine use will count as 1 for the purposes of the number of failed treatments. Exclusion Criteria: Diagnosis of drug-induced SLE rather than idiopathic SLE Other systemic autoimmune diseases (eg, multiple sclerosis, psoriasis, inflammatory bowel disease, etc) are excluded. Participants with type I autoimmune diabetes mellitus, thyroid autoimmune disease, Celiac disease, or secondary Sjögren's syndrome are not excluded SLE overlap syndromes including, but not limited to, rheumatoid arthritis, scleroderma, and mixed connective tissue disease, are excluded Recent or present clinically significant CNS pathology Other protocol-defined Inclusion/Exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of CC-97540<br> | Drug: CC-97540<br>* Specified dose on specified days<br>* Other names: BMS-986353;Drug: Fludarabine<br>* Specified dose on specified days<br>Drug: Cyclophosphamide<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (AEs) |  | Up to 2 years after CC-97540 infusion | 
| Number of participants with serious AEs (SAEs) |  | Up to 2 years after CC-97540 infusion | 
| Number of participants with AEs of special interest (AESI) |  | Up to 2 years after CC-97540 infusion | 
| Number of participants with laboratory abnormalities |  | Up to 2 years after CC-97540 infusion | 
| Number of participants with Dose Limiting Toxicities (DLT) |  | Up to 2 years after CC-97540 infusion | 
| Recommend Phase 2 Dose (RP2D) of CC-97540 |  | Up to 2 years after CC-97540 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving definition of remission in SLE (DORIS) remission |  | At week 24 | 
| Proportion of participants achieving Lupus Low Disease Activity State (LLDAS) |  | At week 24 | 
| Change in proteinuria measured by urine protein creatinine ratio (UPCR) |  | At week 24 | 
| Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) |  | At week 24 | 
| Proportion of participants achieving DORIS remission over time |  | Up to 2 years | 
| Proportion of participants achieving LLDAS over time |  | Up to 2 years | 
| Change in Systemic Lupus Erythematosus Disease Activity- 2000 (SLEDAI-2K) over time |  | Up to 2 years | 
| Change in proteinuria measured by UPCR over time |  | Up to 2 years | 
| Time to the first documentation of DORIS remission |  | Up to 2 years | 
| Time to the first documentation of LLDAS |  | Up to 2 years | 
| Time from CC-97540 infusion to first disease flare, any flare monitoring by Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI (SELENA-SLEDAI) |  | Up to 2 years | 
| Maximum observed blood concentration (Cmax) |  | Up to 2 years | 
| Time of maximum observed blood concentration (Tmax) |  | Up to 2 years | 
| Area under the blood concentration-time curve from time zero to 28 days after dosing (AUC(0-28D)) |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-97540, BMS-986353