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

Официальное название

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

Обзор

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

Вмешательства

• Препарат CLN-978
  Specified dose on specified days

Первичные конечные точки

• Safety and tolerability [Срок оценки: 48 weeks]

Вторичные конечные точки (3)

• Pharmacokinetics [Срок оценки: 48 weeks]
• Immunogenicity [Срок оценки: 48 weeks]
• Pharmacodynamics-related biomarker [Срок оценки: 48 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• AARA Clinical Research — Avondale
• AARA Clinical Research — Tucson
• Omega Research Group — Orlando
• University of Iowa — Iowa City
• Columbia University Medical Center — New York
• University of Rochester Medical Center — Rochester
• Regional One Health — Memphis
• Stryde Research — Plano
• … и ещё 2 центра

Франция · 3 центра

• CHU de Nantes — Nantes
• University Hospital Saint Etienne — Saint-Priest-en-Jarez
• Centre Hospitalier Universitaire de Toulouse — Toulouse

Австралия · 2 центра

• Royal Melbourne Hospital — Parkville
• Osteoporosis Solutions — Victoria Park

Румыния · 2 центра

• ARENSIA Exploratory Medicine S.R.L. — Bucharest
• Arensia Exploratory Medicine — Cluj-Napoca

Болгария · 1 центр

• Multi profile Hospital for Active Treatment Sveta Sofia — Sofia

Грузия · 1 центр

• ARENSIA Exploratory Medicine, LLC — Tbilisi

Moldova · 1 центр

• Timofei Moșneaga Republican Clinical Hospital — Chisinau

Идентификаторы

NCT: NCT06613360 · CLN-978-SL-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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