RESET-SLE: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Subjects With Active Systemic Lupus Erythematosus

Официальное название

A Phase 1/2, Open-label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T Cells (CABA-201) in Subjects With Active Systemic Lupus Erythematosus

Обзор

RESET-SLE: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Subjects With Active Systemic Lupus Erythematosus

Подробное описание

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by autoantibody production and abnormal B cell function. SLE presents with fluctuating severity and may cause tissue damage in a variety of organs over time. Lupus nephritis (LN) (renal involvement) is a common severe manifestation of SLE, which can lead to significant morbidity and mortality. This study is being conducted to evaluate the safety and efficacy of an investigational cell therapy, CABA-201, also called resecabtagene autoleucel, or "rese-cel". Rese-cel can be given to patients with either LN or SLE without renal involvement, in two separate parallel cohorts, who have active disease. Initially a single dose of CABA-201 in patients pretreated with a standard regimen including cyclophosphamide (CY) and fludarabine (FLU), will be evaluated. In addition, escalating doses of CABA-201 will be evaluated in patients without CY and FLU pretreatment.

Вмешательства

• Биопрепарат CABA-201
  Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide
• Биопрепарат CABA-201
  Single intravenous infusion of CABA-201 at escalating dose levels without preconditioning

Первичные конечные точки

• To evaluate incidence of adverse events [Срок оценки: Up to 28 days after CABA-201 infusion]

Вторичные конечные точки (7)

• To evaluate adverse events and laboratory abnormalities [Срок оценки: Up to 156 weeks]
• To characterize the pharmacodynamics (PD) [Срок оценки: Up to 156 weeks]
• To characterize the pharmacokinetics (PK) [Срок оценки: Up to 156 weeks]
• To evaluate disease related biomarkers [Срок оценки: Up to 156 weeks]
• To evaluate disease related biomarkers [Срок оценки: Up to 156 Weeks]
• To evaluate efficacy [Срок оценки: Up to 156 Weeks]
• To evaluate efficacy [Срок оценки: Up to 156 weeks]

Критерии участия

Критерии включения

• Age ≥18 and ≤65
• A clinical diagnosis of SLE, based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult SLE.
• Positive antinuclear antibody (ANA) titer or anti-dsDNA antibody at screening.
• For LN subjects only, active, biopsy-proven LN class III or IV, with or without the presence of class V, according to 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
• For non-renal SLE subjects only: Active, moderate to severe SLE

Критерии исключения

• Contraindication to leukapheresis
• History of anaphylactic or severe systemic reaction to fludarabine, cyclophosphamide or any of their metabolites
• Active infection requiring medical intervention at screening
• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric, cardiac, neurological, or cerebral disease, including severe and uncontrolled infections, such as sepsis and opportunistic infections.
• Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study, interfere with the assessment of the effects or safety of the investigational product or with the study procedures
• For LN subjects only: The presence of kidney disease other than active lupus nephritis
• Previous CAR T cell therapy
• Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant.

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 · 21 центр

• University of California Irvine — Orange
• UC Davis Health — Sacramento
• Yale University — New Haven
• University of Florida Health — Gainesville
• Mayo Clinic — Jacksonville
• Emory University — Atlanta
• Northwestern Memorial Hospital — Chicago
• The University of Chicago Medical Center — Chicago
• … и ещё 13 центров

Канада · 1 центр

• Maisonneuve-Rosemont Hospital — Montreal

Испания · 1 центр

• Clinica Universitaria de Navarra — Pamplona

Идентификаторы

NCT: NCT06121297 · CAB-201-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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