A Study of CLN-978, a Subcutaneously Administered CD19-directed T Cell Engager, in Subjects With Systemic Lupus Erythematosus

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.