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

Phase 2Not Yet RecruitingNCT07729826

AbelZeta Inc.50 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

C-CAR168DRUG

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).

Eligibility

Sex: ALLMin age: 14 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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

Outcomes

Primary Outcomes

Complete Renal Response (CRR)

Proportion of participants achieving Complete Renal Response according to protocol-defined criteria.

Time frame: Week 65 (Month 15)

Secondary Outcomes

Incidence and severity of adverse events (AEs)

Evaluate the incidence, severity, and relationship of adverse events following C-CAR168 infusion, graded according to NCI CTCAE Version 6.0.