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NCT Number: NCT07729826

C-CAR168 CAR T-Cell Therapy 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.

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Key information

Conditions

Lupus Nephritis (LN) Autoimmune Diseases Connective Tissue Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glomerulonephritis Immune System Diseases Kidney Diseases Lupus Erythematosus, Systemic Lupus Nephritis Male Urogenital Diseases Nephritis Skin and Connective Tissue Diseases Systemic Lupus Erythematosus (SLE) Urogenital Diseases Urologic Diseases

Age range

14 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

C-CAR168

Drug

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).

Primary outcomes

  1. Complete Renal Response (CRR)

    Time frame: Week 65 (Month 15)

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

Secondary outcomes

  1. Incidence and severity of adverse events (AEs)

    Time frame: Through Week 104 (Month 24)

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

  2. incidence of serious adverse events (SAEs)

    Time frame: Through Week 104 (Month 24)

    Evaluate the incidence of serious adverse events following treatment.

  3. Incidence and severity of cytokine release syndrome (CRS)

    Time frame: Through Week 104 (Month 24)

    Assess CRS according to American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.

  4. Incidence and severity of immune effector cell-associated neurotoxicity syndrome (ICANS)

    Time frame: Through Week 104 (Month 24)

    Assess ICANS according to ASTCT consensus grading criteria.

  5. Duration of Complete Renal Response (CRR)

    Time frame: Through Week 104 (Month 24)

    Evaluate the maintenance of complete renal response without relapse, flare, or rescue medication.

  6. Partial Renal Response (PRR)

    Time frame: Through Week 104 (Month 24)

    Evaluate the proportion of participants achieving partial renal response.

  7. Primary Efficacy Renal Response (PERR)

    Time frame: Through Week 104 (Month 24)

    Evaluate the proportion of participants achieving Primary Efficacy Renal Response.

  8. Reduction in proteinuria

    Time frame: Through Week 104 (Month 24)

    Evaluate the proportion of participants achieving at least a 75% reduction in urine protein-to-creatinine ratio (uPCR).

  9. Time to renal response

    Time frame: Through Week 104 (Month 24)

    Evaluate the time to achievement of Complete Renal Response, Partial Renal Response, and Primary Efficacy Renal Response.

  10. Pharmacokinetics of C-CAR168 measuring quantitative polymerase chain reaction (qPCR)

    Time frame: Through Week 104 (Month 24)

    Characterize CAR T-cell expansion and persistence using qPCR

  11. Pharmacokinetics of C-CAR168 utilizing flow cytometry

    Time frame: Through Week 104 (Month 24)

    Characterize T-cell expansion and persistence utilizing flow cytometry

  12. Change in patient-reported outcomes (PROs)

    Time frame: Through Week 104 (Month 24)

    Evaluate changes in health-related quality of life using PROs.

  13. DORIS remission

    Time frame: Though Week 104 (Month 24)

    Evaluate the proportion of participants achieving the Definition of Remission in SLE (DORIS).

  14. Progressive renal failure

    Time frame: Through Week 104 (Month 24)

    Evaluate the proportion of participants experiencing progressive renal failure as measured by estimated glomerular filtration rate (eGFR).

  15. Corticosteroid reduction

    Time frame: Through Week 104 (Month 24)

    Evaluate the proportion of participants receiving less than 5 mg/day prednisone equivalent.

  16. Lupus disease flare

    Time frame: Through Week 104 (Month 24)

    Evaluate the proportion of participants experiencing disease flare according to the SELENA-SLEDAI Flare Index.

  17. Immunologic response

    Time frame: Through Week 104 (Month 24)

    Evaluate changes in anti-double stranded DNA antibodies, circulating B cells, plasma cells, and complement C3/C4 levels.

Other outcomes

  1. Exploratory Biomarker Assessments

    Time frame: Through Week 104 (Month 24)

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Kirstin Liechty

CONTACT

[email protected]

240-552-5870

Nurat Quadri

CONTACT

[email protected]

240-552-5870

Sponsors and collaborators

Lead sponsor

AbelZeta Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Jul 28, 2026
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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