Idiopathic Inflammatory Myopathy, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Systemic Sclerosis
Conditions
Keywords
CC-97540, BMS-986353
Brief summary
The purpose of this study is to establish the tolerability, preliminary efficacy, and pharmacokinetics of CC-97540 in participants with severe, refractory autoimmune diseases (Breakfree-1).
Interventions
DRUGCC-97540
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
Bristol-Myers Squibb Services Unlimited 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
\- Diagnosis of Systemic Lupus Erythematosus (SLE) defined as follows:. i) Fulfilling the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria of SLE. ii) Presence of anti-dsDNA, anti-histone, anti-chromatin, anti-Ro (anti-SS-A), anti-La (anti-SS-B), or anti-Sm antibodies at screening. \- SLE disease activity:. i) Active disease at screening, with recent ≥ 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. * Diagnosis of Idiopathic Inflammatory Myopathy (IIM) defined as follows:. i) Fulfilling the 2017 EULAR/ACR classification criteria for probable or definite IIM. ii) Participant diagnosed with the following IIM subgroups: dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), and polymyositis (PM). iii) Presence of at least 1 myositis specific antibody (MSA), associated antibody (MAA), or ANA at screening or prior to screening. * IIM disease activity:. i) Severe/moderate muscle AND/OR skin involvement. ii) Proof of activity as documented by:. A. An active myositis-associated rash OR. B. A recent muscle biopsy OR. C. An elevated CK \> 3 times the upper limit of normal OR. D. Participants diagnosed IIM AND progressive Interstitial Lung Disease (ILD) on high-resolution computed tomography (HRCT) iii) Inadequate response to glucocorticoids and at least 2 of the following treatments used for at least 3 months: azathioprine, methotrexate, cyclosporin A, tacrolimus, MMF, cyclophosphamide, IVIG, JAK inhibitors, and rituximab. * Diagnosis of Systemic Sclerosis (SSc) defined as follows:. i) Fulfilling 2013 EULAR/ACR classification criteria for SSc. ii) Antinuclear Antibody (ANA) positive at screening or prior to screening. \- SSc disease activity:. i) Participants diagnosed with diffuse cutaneous SSc OR diffuse or limited cutaneous SSc AND progressive ILD, AND. ii) Inadequate response to at least 1 of the following treatments used for at least 3 months: mycophenolate, cyclophosphamide, rituximab, nintedanib, azathioprine, tocilizumab, or intravenous immunoglobulins (IVIG). \- Rheumatoid Arthritis (RA) disease activity:. i) Minimum of 3 SJC and 3 TJC on a 66/68 joint count (SJC/TJC). ii) OR participants diagnosed with progressive ILD (interstitial lung disease). iii) AND Inadequate disease response or intolerance to at least one conventional synthetic disease-modifying antirheumatic drug (DMARD) and as well as ≥ 2 DMARDs with different mechanisms of action from the categories biologic disease-modifying antirheumatic drug (bDMARDs) or targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) for a minimum of 3 months. A. Participants qualifying on progressive ILD may have exhausted the therapies above OR have demonstrated inadequate disease response or intolerance to at least one of the following treatments used for at least 3 months: mycophenolate, tocilizumab, cyclophosphamide, rituximab, azathioprine, nintedinib, pirfenidone.
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. * Present or recent clinically significant CNS pathology, within 12 months. * IIM disease activity:. i) Other forms of IIM: Inclusion Body Myositis, Amyopathic DM, any form of juvenile myositis. ii) Myositis other than IIM, eg, drug-induced myositis and PM associated with HIV. iii) Participants with severe muscle damage (Physician VAS for muscle damage in Myositis Damage Index \> 7 cm on a 10 cm scale), permanent weakness due to a non-IIM cause (eg, stroke), or myositis with cardiac involvement. \- SSc disease activity:. i) SSc related PAH requiring active treatment. ii) Rapidly progressive SSc related lower GI (small and large intestines) involvement (requiring parenteral nutrition); active gastric antral vascular ectasia. iii) Prior scleroderma renal crisis. \- RA disease activity:. i) Prior history of or current inflammatory joint disease other than RA. ii) Joint damage and/or deformity that may confound the investigator's ability to accurately assess disease activity. \- Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with treatment-emergent adverse events (AEs) in each indication. | Up to 2 years after CC-97540 infusion |
| Number of participants with serious AEs (SAEs) in each indication. | Up to 2 years after CC-97540 infusion |
| Number of participants with AEs of special interest (AESI) in each indication. | Up to 2 years after CC-97540 infusion |
| Number of participants with laboratory abnormalities in each indication. | Up to 2 years after CC-97540 infusion |
| Number of participants with Dose Limiting Toxicities (DLT) in each indication. | Up to 2 years after CC-97540 infusion |
| Recommended Phase 2 Dose (RP2D) of CC-97540 in each indication. | Up to 2 years after CC-97540 infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving definition of remission in SLE (DORIS) remission | At week 24 | SLE Cohort |
| Proportion of participants achieving Lupus Low Disease Activity State (LLDAS) | At week 24 | SLE Cohort |
| Change in proteinuria measured by urine protein creatinine ratio (UPCR) | At week 24 | SLE Cohort |
| Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) | At week 24 | — |
| Proportion of participants achieving Myositis Response Criteria (MRC) Total Improvement Score (TIS) Major Response | At Week 24 | IIM Cohort |
| Change in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) | At Week 24 | Only Dermatomyositis (DM) participants in the IIM Cohort |
| Proportion of participants with ILD with no worsening of pulmonary function including forced expiratory volume (FEV1) (> 10%), forced vital capacity (FVC) (> 10%), and diffusing capacity of the lung for carbon monoxide (DLCO) (> 15%) | At Week 24 | IIM Cohort |
| Proportion of participants achieving a minimal clinically important difference (MCID) of 24% change from baseline of the modified Rodnan Skin Score (mRSS) | At Week 24 | SSc Cohort |
| Participants with an improvement from baseline of the Revised Composite Response Index in Systemic Sclerosis (CRISS) | At Week 24 | SSc Cohort |
| The worsening of pulmonary function including FVC (>10% absolute), DLCO (>15% absolute decline) in participants with interstitial lung disease (ILD) | At Week 24 | SSc Cohort |
| Proportion of participants achieving low Disease Activity Score-28 Joint C-Reactive Protein (DAS28-CRP) | At week 24 | RA cohort |
| Proportion of participants achieving simplified disease activity index (SDAI) remission | At week 24 | RA cohort |
| Proportion of participants with ILD with no worsening of pulmonary function including FVC (> 10%) | At week 24 | RA cohort |
| 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 | — |
Countries
Belgium, France, Germany, Italy, Spain, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed