a study of cln-978, a subcutaneously administered cd19-directed t cell engager, in subjects with systemic lupus erythematosus

Conditions: SLE; SLE (Systemic Lupus)

Summary: phase 1b, open-label study of cln-978 administered subcutaneously in patients with moderate to severe systemic lupus erythematosus (sle).


Eligibility criteria:
inclusion criteria: * diagnosis of sle at least 24 weeks prior to screening and meet 2019 eular / acr classification criteria at screening. * presence of one or more of the following autoantibodies documented during screening: positive anti-nuclear antibody (ana) test (≥1:80); anti dsdna above the upper limit of normal (uln); anti-sm above the uln. * active sle disease, as demonstrated by a sledai total score ≥8 at screening. * inadequate response to at least 2 of the following treatments: oral corticosteroid, antimalarials, conventional immunosuppressants, or biologics. at least one of the failed treatments should be an immunosuppressive or biologic standard-of care agent. * if on corticosteroid and/or antimalarial, the dose must be stable prior to day 1. * laboratory parameters including the following: * absolute lymphocyte count (alc) ≥0.5 x 109/l * peripheral cd19+ b cell count ≥25 cells/µl * absolute neutrophil count (anc) ≥1.0 x 109/l * hemoglobin ≥8 g/dl * platelet count ≥75 x 109/l. * estimated glomerular filtration rate (egfr) (based on ckd-epi formula) ≥30 ml/min/1.73m2 * total bilirubin ≤1.5 × uln, except patients with confirmed gilbert's syndrome * aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤2.5 × uln * serum albumin \>2.8 g/dl * part b only: for patients who were treated in part a and did not experience dose-limiting toxicity (dlt) or discontinue cln-978 treatment due to aes are eligible for retreatment at a higher dose or longer schedule in part b if they otherwise meet eligibility criteria and at least 90 days have passed since the last dose of cln-978. exclusion criteria: * active inflammatory disease other than sle. thyroiditis or secondary sjogren's syndrome is allowed. * considered at high risk for thrombosis. * rapidly progressive glomerulonephritis, and/or urine protein/creatinine \>3 mg/mg (339 mg/mmol). * active severe neuropsychiatric/cns manifestations of sle. * evidence of hepatitis b, hepatitis c (hcv) infection, human immunodeficiency virus (hiv), epstein-barr virus (ebv), or cytomegalovirus (cmv) infection. * history of splenectomy. * prior treatment with the following: * cellular or gene therapy product directed at any target. * investigational therapy within 30 days or 5 drug-elimination half-lives (whichever is longer) prior to day 1. * any anti-cd19 or anti-cd20 therapy less than 3 months prior to day 1. * non-biologic dmard within 14 days prior to day 1. * cyclophosphamide or a biologic immunomodulating therapy during 2 months prior to day 1. * live or attenuated vaccine within 28 days prior to screening or during screening. * active, clinically significant bacterial, viral, fungal, mycobacterial, parasitic, or other infection, including sars-cov-2 infection, within 14 days before day 1. * active or latent tuberculosis (tb) evidenced by a positive or indeterminant interferon gamma release assay (igra), unless the patient has documented previous completion of tb treatment and no current clinical indication of tb. * any condition for which, in the opinion of the investigator and/or sponsor, would not be in the best interest of the patient to participate in the study or that could prevent, limit, or confound any protocol-defined assessment.

Keywords: systemic lupus erythematosus