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

A Phase 1b, Open-label, Pilot Study of CLN-978 for the Treatment of Moderate to Severe Systemic Lupus Erythematosus (SLE)

Phase 1b, open-label study of CLN-978 administered subcutaneously in patients with Moderate to Severe Systemic Lupus Erythematosus (SLE).

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 or in the previous 12 months before 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 ≥6 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 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

• 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 within 1 month 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.