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Phase 1
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18+Age Range
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42Locations
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Recruiting
Recruiting
A Study of CC-97540, CD-19-Targeted Nex-T CAR T Cells, in Participants With Severe, Refractory Autoimmune Diseases
The purpose of this study is to establish the tolerability, preliminary efficacy, and pharmacokinetics of CC-97540 in participants with severe, refractory autoimmune diseases.
Inclusion Criteria - Diagnosis of Systemic Lupus Erythematosus (SLE) defined as follows:. i) Fulfilling the 2019 ACR/EULAR classification criteria of SLE. ii) Presence of anti-dsDNA, anti-histone, anti-chromatin, or anti-Sm antibodies. - SLE disease activity. i) 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. A. Insufficient response is defined as lack of response, insufficient response or lack of sustained response to appropriate doses. Intolerance is not considered insufficient response. B. Methotrexate and azathioprine use will count as 1 for the purposes of the number of failed treatments. - Diagnosis of Idiopathic Inflammatory Myopathy (IIM) defined as follows:. i) Fulfilling the 2017 ACR/EULAR classification criteria for probable or definite IIM. A. Definite: total aggregate score of ≥ 7.5 without muscle biopsy and ≥ 8.7 with muscle biopsy. B. Probable: score of 5.5 without biopsies; 6.7 with biopsies. ii) Participant diagnosed with the following IIM subgroups: DM, immune-mediated necrotizing myopathy (IMNM), and anti-synthetase syndrome (ASyS) must also meet the following criteria:. A. DM: history of heliotrope rash or Gottron's papules. B. IMNM: typical muscle biopsy or prior history of either anti-HMGCR or anti-SRP autoAb. C. ASyS: defined as the history of anti-synthetase autoantibody and at least 2 of the following: ILD, inflammatory myositis or inflammatory polyarthritis. iii) Presence of at least 1 myositis specific (MSA), associated antibody (MAA), or ANA at screening or prior to screening. - IIM disease activity. i) Severe muscle AND/OR skin involvement defined as:. A. Manual Muscle Test < 130 (severe) OR. B. Cutaneous Dermatomyositis Disease Area and Severity Index of > 19 for skin AND MMT-8 < 142. ii) Proof of activity as documented by:. A. An active myositis-associated rash (Gottron's papules or heliotrope rash) OR. B. A recent (within 3 months prior to signing informed consent) biopsy, magnetic resonance imaging, or electromyogram demonstrating active disease OR. C. An elevated CK > 3 times the upper limit of normal at screening with no alternate explanation or cause. 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, leflunomide, IVIG, and rituximab. A. Insufficient response is defined as lack of response, insufficient response or lack of sustained response to appropriate doses. Intolerance is not considered insufficient response. - Diagnosis of Systemic Sclerosis (SSc) defined as follows:. i) Fulfilling 2013 ACR and European League Against Rheumatism classification criteria for SSc. ii) Antinuclear Antibody (ANA) positive at screening or prior to screening. - SSc disease activity. i) Participant diagnosed with diffuse SSc meeting the following criteria:. A. Disease duration ≤ 5 years (from onset of first non-Raynaud manifestation) AND. B. mRSS ≥ 15 at screening AND. C. mRSS increase ≥ 3 units or involvement of 1 new body area, or mRSS increase ≥ 2 units in 1 body area over 6 months AND. D. At least one: C-reactive protein ≥ 10·0 mg/L, erythrocyte sedimentation rate ≥ 28 mm/h, OR Health Assessment Questionnaire - Disability Index (HAQ-DI) > 1.0. ii) Participants diagnosed with diffuse or limited cutaneous SSc AND progressive ILD on HRCT and ≤ 5 years duration (from onset of first non-Raynaud manifestation) defined by either (a) or (b). a. Progressive ILD as defined by Raghu et al (≥ 2 of the following):. i) worsening respiratory symptoms ii) physiological evidence of disease progression (≥ 1 of the following):. A. Absolute decline in FVC ≥ 5% predicted within 1 year of follow-up. B. Absolute decline in DLCO (corrected for Hb) ≥ 10% predicted within 1 year of follow-up radiological evidence of disease progression. C. Increased extent or severity of traction bronchiectasis and bronchiolectasis. D. New ground-glass opacity with traction bronchiectasis. E. New fine reticulation. F. Increased extent or increased coarseness of reticular abnormality. G. New or increased honeycombing. H. Increased lobar volume loss. b. FVC < 80% predicted and moderate to severe ILD, as assessed by a radiologist. iii) Inadequate response to at least 1 of the following treatments used for at least 3 months: mycophenolate, cyclophosphamide, rituximab, or tocilizumab. A. Insufficient response is defined as lack of response, insufficient response or lack of sustained response to appropriate doses. Intolerance is not considered insufficient response. 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. - 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. - Other protocol-defined Inclusion/Exclusion criteria apply.
Experimental: Administration of CC-97540