C-CAR168 CAR T-Cell Therapy for the Treatment of Lupus Nephritis Refractory to Standard Therapy

Официальное название

Multi-center, Phase 2 Clinical Study of an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T Cell Therapy (C-CAR168) for the Treatment of Lupus Nephritis Refractory to Standard Therapy

Обзор

This Phase 2, multicenter, open-label study will evaluate the safety and efficacy of a single infusion of autologous anti-CD20/BCMA chimeric antigen receptor T cells (C-CAR168) following lymphodepleting chemotherapy in participants with refractory lupus nephritis who are not responding to standard therapy. Approximately 50 participants will undergo leukapheresis, lymphodepletion with fludarabine and cyclophosphamide, and infusion of C-CAR168. Participants will be followed for 104 weeks (approximately 2 years) to evaluate renal response, safety, CAR T-cell persistence, pharmacokinetics/pharmacodynamics, and biomarkers. Long-term safety follow-up for gene therapy-related events will continue for up to 15 years following CAR T-cell infusion.

Подробное описание

This is a global, multicenter, single-arm, open-label Phase 2 study evaluating C-CAR168, an autologous dual-targeted anti-CD20/BCMA CAR T-cell therapy, in participants with biopsy-confirmed refractory lupus nephritis who are not responding to standard therapy.

Participants will undergo screening, leukapheresis, manufacture of autologous C-CAR168, lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide, followed by a single intravenous infusion of C-CAR168.

The study begins with a safety run-in involving the first five participants. Following review by the Safety Monitoring Committee (SMC), enrollment of the remaining participants may proceed if predefined safety criteria are met.

Participants will be followed for 104 weeks after infusion for evaluation of efficacy, safety, pharmacokinetics, pharmacodynamics, immunologic biomarkers, and patient-reported outcomes. Participants will subsequently be invited to enroll in a separate long-term follow-up study for continued safety monitoring consistent with FDA recommendations for gene-modified cellular therapies.

Вмешательства

• Препарат C-CAR168
  Autologous anti-CD20/BCMA chimeric antigen receptor T-cell therapy administered as a single intravenous infusion at a target dose of 1 × 10\^6 CAR-positive T cells/kg (maximum dose 100 × 10\^6 CAR-positive T cells).

Первичные конечные точки

• Complete Renal Response (CRR) [Срок оценки: Week 65 (Month 15)]

Вторичные конечные точки (12)

• Incidence and severity of adverse events (AEs) [Срок оценки: Through Week 104 (Month 24)]
• incidence of serious adverse events (SAEs) [Срок оценки: Through Week 104 (Month 24)]
• Incidence and severity of cytokine release syndrome (CRS) [Срок оценки: Through Week 104 (Month 24)]
• Incidence and severity of immune effector cell-associated neurotoxicity syndrome (ICANS) [Срок оценки: Through Week 104 (Month 24)]
• Duration of Complete Renal Response (CRR) [Срок оценки: Through Week 104 (Month 24)]
• Partial Renal Response (PRR) [Срок оценки: Through Week 104 (Month 24)]
• Primary Efficacy Renal Response (PERR) [Срок оценки: Through Week 104 (Month 24)]
• Reduction in proteinuria [Срок оценки: Through Week 104 (Month 24)]
• Time to renal response [Срок оценки: Through Week 104 (Month 24)]
• Pharmacokinetics of C-CAR168 measuring quantitative polymerase chain reaction (qPCR) [Срок оценки: Through Week 104 (Month 24)]
• Pharmacokinetics of C-CAR168 utilizing flow cytometry [Срок оценки: Through Week 104 (Month 24)]
• Change in patient-reported outcomes (PROs) [Срок оценки: Through Week 104 (Month 24)]

Критерии участия

Критерии включения

• Able to provide informed consent or assent where applicable.
• Male or female aged 14-70 years, weighing at least 40 kg.
• Diagnosis of systemic lupus erythematosus according to the 2019 EULAR/ACR classification criteria.
• Biopsy-confirmed ISN/RPS Class III or IV lupus nephritis, with or without Class V, within 6 months before screening.
• Proteinuria meeting protocol-defined thresholds.
• Refractory to standard therapy.
• Meets corticosteroid taper requirements.
• Positive ANA and/or anti-dsDNA and/or anti-Smith antibody.
• Meets all protocol eligibility requirements.

Критерии исключения

• Active uncontrolled infection
• Active hepatitis B, hepatitis C, or HIV infection
• Active tuberculosis
• Pregnancy or breastfeeding
• Prior gene therapy or CAR T-cell therapy
• Active malignancy
• Severe cardiovascular disease
• Significant pulmonary disease
• CNS disease precluding participation
• Any condition that would interfere with study participation or safety

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07729826 · ABZT-421 · IND 30283 · C-CAR168

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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