SLE, SLE (Systemic Lupus)
Conditions
Keywords
Systemic Lupus Erythematosus
Brief summary
Phase 1b, open-label study of CLN-978 administered subcutaneously in patients with Moderate to Severe Systemic Lupus Erythematosus (SLE).
Interventions
DRUGCLN-978
Specified dose on specified days
Sponsors
Cullinan Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | 48 weeks | Incidence and severity of adverse events (AEs)/adverse events of special interest (AESIs)/serious adverse events (SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics | 48 weeks | Serum concentrations of CLN-978 |
| Immunogenicity | 48 weeks | Level of anti-drug antibodies |
| Pharmacodynamics-related biomarker | 48 weeks | Levels of total B lymphocytes in the peripheral blood |
Countries
Australia, Bulgaria, France, Georgia, Moldova, Romania, United States
Contacts
CONTACTMeagan Sardinha
Outcome results
None listed