Lupus Nephritis (LN)Phase 2NCT07729826
C-CAR168, an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy, in Participants With Lupus Nephritis Refractory to Standard Therapy
A Phase 2 study testing C-CAR168 in people with Lupus Nephritis (LN) and Systemic Lupus Erythematosus (SLE), run by AbelZeta Inc..
Trial summary
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. Read more about this study
- Who is it for?
- Ages 14 to 70 years
- Conditions the study is for
- Lupus Nephritis (LN), Systemic Lupus Erythematosus (SLE), Autoimmune Diseases
- What is being tested?
- C-CAR168
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2026to 1 Sep 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- Meets corticosteroid taper requirements.
- Positive ANA and/or anti-dsDNA and/or anti-Smith antibody.
- Meets all protocol eligibility requirements.
Who cannot join
- 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
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- Severe cardiovascular disease
- Significant pulmonary disease
- CNS disease precluding participation
- Any condition that would interfere with study participation or safety
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official 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
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.
Read the 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.
- Being tested
- C-CAR168
- Keywords
- Lupus Nephritis, Systemic Lupus Erythematosus, CAR T, CAR-T Cell Therapy, CD20, BCMA, Autoimmune Disease, Cell Therapy, CAR-T, CAR-T Therapy, LN, SLE, CAR T-cell therapy, CAR T-cell, chimeric antigen receptor T-cell therapy, lupus, Lupus Nephritis (LN), adolescent
- Medical subject headings
- Lupus Nephritis, Lupus Erythematosus, Systemic, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
| Study group | Role | What they receive |
|---|---|---|
| C-CAR168 | Experimental | Participants will receive:
* Leukapheresis
* Fludarabine
* Cyclophosphamide
* Single intravenous infusion of C-CAR168 Receives: Drug: C-CAR168 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Renal Response (CRR)
Proportion of participants achieving Complete Renal Response according to protocol-defined criteria.
Measured: Week 65 (Month 15)
Secondary outcomes (17)
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.
Measured: Through Week 104 (Month 24)
incidence of serious adverse events (SAEs)
Evaluate the incidence of serious adverse events following treatment.
Measured: 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.
Measured: Through Week 104 (Month 24)
Incidence and severity of immune effector cell-associated neurotoxicity syndrome (ICANS)
Assess ICANS according to ASTCT consensus grading criteria.
Measured: Through Week 104 (Month 24)
Duration of Complete Renal Response (CRR)
Evaluate the maintenance of complete renal response without relapse, flare, or rescue medication.
Measured: Through Week 104 (Month 24)
Partial Renal Response (PRR)
Evaluate the proportion of participants achieving partial renal response.
Measured: Through Week 104 (Month 24)
Primary Efficacy Renal Response (PERR)
Evaluate the proportion of participants achieving Primary Efficacy Renal Response.
Measured: 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).
Measured: 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.
Measured: Through Week 104 (Month 24)
Pharmacokinetics of C-CAR168 measuring quantitative polymerase chain reaction (qPCR)
Characterize CAR T-cell expansion and persistence using qPCR
Measured: Through Week 104 (Month 24)
Pharmacokinetics of C-CAR168 utilizing flow cytometry
Characterize T-cell expansion and persistence utilizing flow cytometry
Measured: Through Week 104 (Month 24)
Change in patient-reported outcomes (PROs)
Evaluate changes in health-related quality of life using PROs.
Measured: Through Week 104 (Month 24)
DORIS remission
Evaluate the proportion of participants achieving the Definition of Remission in SLE (DORIS).
Measured: 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).
Measured: Through Week 104 (Month 24)
Corticosteroid reduction
Evaluate the proportion of participants receiving less than 5 mg/day prednisone equivalent.
Measured: Through Week 104 (Month 24)
Lupus disease flare
Evaluate the proportion of participants experiencing disease flare according to the SELENA-SLEDAI Flare Index.
Measured: 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.
Measured: Through Week 104 (Month 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2026
- Study start30 Sep 2026 (estimated)
- Primary completion31 Dec 2028 (estimated)
- Study completion1 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lupus Nephritis (LN)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All enrolled participants receive lymphodepleting chemotherapy followed by a single infusion of C-CAR168.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AbelZeta Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott Antonia, MD, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07729826
- Sponsor's protocol ID
- ABZT-421
- Other IDs
- IND 30283, C-CAR168
- Status last verified
- Oct 2026
- First submitted
- 16 Jul 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data collected during this study will not be made available to other researchers.