About this trial

The purpose of this clinical trial is to evaluate the safety and efficacy of CRC01, an investigational autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, in people with lupus nephritis (LN), a serious kidney complication of systemic lupus erythematosus (SLE).

The main objectives of the study are:

1. To determine whether CRC01 infusion can improve kidney outcomes and reduce disease activity in participants with lupus nephritis. 2. To assess the safety profile, including potential risks such as cytokine release syndrome (CRS) and neurotoxicity.

Study Design This is a single-arm, open-label, multi-center, Phase 1/2 study. All enrolled participants will receive CRC01 after screening and baseline assessments.

Study Procedures

Participants will:

* Undergo eligibility screening, including blood tests, urine tests, and disease activity assessments. * Provide autologous T lymphocytes through a procedure called leukapheresis. * Receive a lymphodepleting pre-conditioning regimen (short course of chemotherapy). * Receive a single intravenous infusion of CRC01 cells. * Be hospitalized for close monitoring to detect and manage early adverse events such as CRS or neurotoxicity. * Return for scheduled follow-up assessments through Week 52 (12 months) post-infusion to evaluate safety and treatment response.

Key Outcomes

Researchers will measure:

* Changes in proteinuria and kidney function. * Changes in disease activity scores. * Incidence and severity of adverse events.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 19 years or older, voluntarily provides written informed consent.

Diagnosis of systemic lupus erythematosus (SLE) according to the 2019 EULAR/ACR classification criteria.

Positive antinuclear antibody (ANA) at screening (titer ≥1:80).

Diagnosis of lupus nephritis Class III or IV (with or without concurrent Class V), confirmed by kidney biopsy within 1 year prior to screening based on ISN/RPS 2018 criteria.

Disqualifiers

Current or anticipated requirement for renal dialysis during the study.

History of kidney transplantation or planned transplantation during the study.

History of severe CNS lupus or currently active severe CNS lupus.

Prior CAR-T cell therapy.

Trial design

Design model

Single group

Treatments tested in this trial

CRC01
Biological/Vaccine
Autologous T lymphocytes genetically modified to express anti-CD19 chimeric antigen receptor (CAR). Administered as a single intravenous infusion.

Treatment groups

39 Participants

are divided into 1 treatment group

Group A: CRC01Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Phase 1 Study: To evaluate the tolerability of CRC01 in patients with severe refractory autoimmune disease (systemic lupus erythematosus), and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)

Safety and tolerability will be assessed by: 1\. Number of participants with dose-limiting toxicities (DLTs) within 28 days after CRC01 infusion, as assessed by CTCAE v5.0 and ASTCT consensus criteria.

Time frame

28 day

2

Phase 1 Study: To evaluate the tolerability of CRC01 in patients with severe refractory autoimmune disease (systemic lupus erythematosus), and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)

Safety and tolerability will be assessed by: 2\. Determination of the maximum tolerated dose (MTD) defined as the highest dose level at which ≤1 of 6 participants experience a DLT.

Time frame

28 day

3

Phase 1 Study: To evaluate the tolerability of CRC01 in patients with severe refractory autoimmune disease (systemic lupus erythematosus), and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)

Safety and tolerability will be assessed by: 3\. Determination of the recommended Phase 2 dose (RP2D) based on incidence of DLTs, safety profile, and investigator/sponsor assessment.

Time frame

28 day

4

Phase 2 Study: To evaluate the efficacy of CRC01 by assessing Complete Renal Response (CRR)

Complete Renal Response (CRR): Defined as meeting all of the following criteria: 1\. 24-hour urine protein ≤0.5 g, or urine protein-to-creatinine ratio (UPCR) ≤0.5. If a 24-hour urine collection is available and meets adequacy criteria, 24-hour urine protein assessment takes precedence. If the 24-hour urine collection is inadequate or not performed, UPCR will be used for evaluation.

Time frame

24 weeks

Secondary outcomes

1

Complete Renal Response (CRR) or Partial Renal Response (PRR) at each assessment Visit

PRR is defined as ≥50% reduction in UPCR compared with baseline.

Time frame

Up to Week 52

2

Change From Baseline in Urine Protein-to-Creatinine Ratio (UPCR)

Change from baseline in UPCR measured in urine (mg/mg)

Time frame

up to Week 52

3

Change From Baseline in Serum Creatinine

Change from baseline in serum creatinine. Unit of measure (mg/dL)

Time frame

up to Week 52

4

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)

Change from baseline in eGFR. Unit of measure: mL/min/1.73 m²

Time frame

up to Week 52

Locations

This trial has no locations.

Efficacy and Safety of CRC01 in Participants With Severe, Refractory Systemic Lupus Erythematosus

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Locations

Sponsors and contacts