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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Lupus Erythematosus (SLE); Lupus Nephritis (LN)
• Intervention / Treatment: Drug: C-CAR168

Detailed Description

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
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kirstin Liechty; Phone Number: 240-552-5870; Email: kirstin.liechty@abelzeta.com
• Study Contact Backup: Name: Nurat Quadri; Phone Number: 240-552-5870; Email: clinicaltrials@abelzeta.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C-CAR168; Participants will receive: Leukapheresis; Fludarabine; Cyclophosphamide; Single intravenous infusion of C-CAR168	Drug: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Renal Response (CRR)	Proportion of participants achieving Complete Renal Response according to protocol-defined criteria.	Week 65 (Month 15)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Through Week 104 (Month 24)
incidence of serious adverse events (SAEs)	Evaluate the incidence of serious adverse events following treatment.	Through Week 104 (Month 24)
Incidence and severity of cytokine release syndrome (CRS)	Assess CRS according to American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.	Through Week 104 (Month 24)
Incidence and severity of immune effector cell-associated neurotoxicity syndrome (ICANS)	Assess ICANS according to ASTCT consensus grading criteria.	Through Week 104 (Month 24)
Duration of Complete Renal Response (CRR)	Evaluate the maintenance of complete renal response without relapse, flare, or rescue medication.	Through Week 104 (Month 24)
Partial Renal Response (PRR)	Evaluate the proportion of participants achieving partial renal response.	Through Week 104 (Month 24)
Primary Efficacy Renal Response (PERR)	Evaluate the proportion of participants achieving Primary Efficacy Renal Response.	Through Week 104 (Month 24)
Reduction in proteinuria	Evaluate the proportion of participants achieving at least a 75% reduction in urine protein-to-creatinine ratio (uPCR).	Through Week 104 (Month 24)
Time to renal response	Evaluate the time to achievement of Complete Renal Response, Partial Renal Response, and Primary Efficacy Renal Response.	Through Week 104 (Month 24)
Pharmacokinetics of C-CAR168 measuring quantitative polymerase chain reaction (qPCR)	Characterize CAR T-cell expansion and persistence using qPCR	Through Week 104 (Month 24)
Pharmacokinetics of C-CAR168 utilizing flow cytometry	Characterize T-cell expansion and persistence utilizing flow cytometry	Through Week 104 (Month 24)
Change in patient-reported outcomes (PROs)	Evaluate changes in health-related quality of life using PROs.	Through Week 104 (Month 24)
DORIS remission	Evaluate the proportion of participants achieving the Definition of Remission in SLE (DORIS).	Though Week 104 (Month 24)
Progressive renal failure	Evaluate the proportion of participants experiencing progressive renal failure as measured by estimated glomerular filtration rate (eGFR).	Through Week 104 (Month 24)
Corticosteroid reduction	Evaluate the proportion of participants receiving less than 5 mg/day prednisone equivalent.	Through Week 104 (Month 24)
Lupus disease flare	Evaluate the proportion of participants experiencing disease flare according to the SELENA-SLEDAI Flare Index.	Through Week 104 (Month 24)
Immunologic response	Evaluate changes in anti-double stranded DNA antibodies, circulating B cells, plasma cells, and complement C3/C4 levels.	Through Week 104 (Month 24)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Biomarker Assessments	Evaluate exploratory biomarkers associated with treatment with C-CAR168 and their relationship to efficacy and safety. Biomarkers include C-CAR168-related and disease-related markers in blood, urine, and optional tissue specimens, including immune cell populations, gene expression, cytokines, and urinary biomarkers.	Through Week 104 (Month 24)

Collaborators and Investigators

• Sponsor: AbelZeta Inc.
• Investigators: Principal Investigator: Scott Antonia, MD, PhD, Duke University

Publications and helpful links

Helpful Links

• AbelZeta Presents New Data on C-CAR168 for the Treatment of Autoimmune Diseases at LUPUS 2025

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: July 16, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 28, 2026

Study Record Updates

• Last Update Posted (Actual): July 28, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Systemic Lupus Erythematosus; CAR T; CD20; Autoimmune Disease; BCMA; Lupus Nephritis; CAR-T Cell Therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Autoimmune Diseases
• Other Study ID Numbers: ABZT-421; IND 30283 (Other Identifier: FDA); C-CAR168 (Other Identifier: AbelZeta Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data collected during this study will not be made available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No