a study of cc-97540, cd-19-targeted nex-t car t cells, in participants with severe, refractory autoimmune diseases (breakfree-1)

Conditions: Systemic Lupus Erythematosus; Idiopathic Inflammatory Myopathy; Systemic Sclerosis

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).


Eligibility criteria:
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 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). 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. - other protocol-defined inclusion/exclusion criteria apply.

Keywords: cc-97540 bms-986353