A Study of CLN-978, a Subcutaneously Administered CD19-directed T Cell Engager, in Subjects With Systemic Lupus Erythematosus
Purpose
Phase 1b, open-label study of CLN-978 administered subcutaneously in patients with Moderate to Severe Systemic Lupus Erythematosus (SLE).
Conditions
- SLE
- SLE (Systemic Lupus)
Eligibility
- Eligible Ages
- Between 18 Years and 70 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part A Dose Escalation |
Patients with SLE treated with CLN-978 in dose escalation cohorts |
|
|
Experimental Part B Further Dose Evaluation |
Further evaluation of CLN-978 treatment of patients with SLE |
|
Recruiting Locations
Cullinan Investigative Site
Avondale, Arizona 85392
Avondale, Arizona 85392
Cullinan Investigative Site
Tucson, Arizona 85704
Tucson, Arizona 85704
Cullinan Investigative Site
Orlando, Florida 32808
Orlando, Florida 32808
Cullinan Investigative Site
Iowa City, Iowa 52242
Iowa City, Iowa 52242
Cullinan Investigative Site
New York, New York 10032
New York, New York 10032
Cullinan Investigative Site
Rochester, New York 14642
Rochester, New York 14642
Cullinan Investigative Site
Memphis, Tennessee 38163
Memphis, Tennessee 38163
Cullinan Investigative Site
Plano, Texas 75093
Plano, Texas 75093
Cullinan Investigative Site
Webster, Texas 77598
Webster, Texas 77598
Cullinan Investigative Site
Salt Lake City, Utah 84101
Salt Lake City, Utah 84101
More Details
- Status
- Recruiting
- Sponsor
- Cullinan Therapeutics Inc.