C-CAR168 CAR T Cell Therapy for Refractory Autoimmune Disease

NCT06935474 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: ABZT-411
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This multi-center, open-label, Phase 1/2 study aims to evaluate the safety, tolerability, and preliminary efficacy of C-CAR168, an autologous anti-CD20/BCMA CAR-T therapy, in patients with autoimmune diseases refractory to standard treatments. The study includes both dose escalation and dose expansion phases, with participants grouped into condition-specific cohorts. The purpose of this study is to:

• Undergo screening to determine eligibility based on entry criteria.
• Taper steroid use before leukapheresis.
• Undergo leukapheresis for the manufacturing of C-CAR168.
• Temporarily discontinue immunosuppressive therapy at least 7 days prior to leukapheresis.
• Receive bridging therapy (steroids) if necessary to maintain disease stability during C-CAR168 manufacturing.
• Undergo lymphodepletion therapy with fludarabine and cyclophosphamide.
• Receive a single intravenous infusion of C-CAR168 at the assigned dose level on Day 0.
• Attend regular safety and efficacy assessments for up to 24 months post-infusion.
• Undergo dose-limiting toxicity evaluation during the first 28 days post-infusion (for those in the dose escalation phase).
• Follow withdrawal procedures if necessary, including a discharge visit within 14 days if their condition deteriorates, unacceptable toxicity occurs, they no longer meet criteria, or they choose to withdraw.

Conditions

Lupus Nephritis (LN)

Keywords

Autoimmune; Lupus Nepritis; Systemic Lupus Erythematosus; CAR-T; CD20; C-CAR168; BCMA

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events or Dose Limiting Toxicities

  The number and severity of Adverse Events (AE) and Serious Adverse Events (SAE), including dose limiting toxicities (DLTs) will be recorded.

  Up to 24 months

Secondary Outcomes (12)

• To evaluate the efficacy of C-CAR168

  Up to 24 months

• To evaluate the efficacy of C-CAR168

  Up to 24 months

• To evaluate the efficacy of C-CAR168

  Up to 24 months

• Renal Related Events

  Up to 24 months

• Time to Response

  Up to 24 months

Study Arms (5)

Arm 2: Dose Level 1 (DL1)

EXPERIMENTAL

Dose: 0.75 × 10⁶ CAR+ cells/kg Starting dose for escalation phase. First 3 subjects must be staggered by 28 days.

Biological: C-CAR168

Arm 3: Dose Level 2 (DL2)

EXPERIMENTAL

Dose: 1.5 × 10⁶ CAR+ cells/kg Second dose level in escalation phase. Subject enrollment staggered by 28 days.

Biological: C-CAR168

Arm 1: Dose Level -1 (DL-1)

EXPERIMENTAL

0.5 × 10⁶ CAR+ cells/kg Optional dose level, administered only upon Safety Review Committee (SRC) recommendation.

Biological: C-CAR168

Arm 4: Dose Level 3 (DL3)

EXPERIMENTAL

Dose: 2.0 × 10⁶ CAR+ cells/kg Optional dose level pending SRC review and approval.

Biological: C-CAR168

Arm 5: Dose Expansion Cohort

EXPERIMENTAL

Dose: To be selected based on MTD/RD identified in escalation phase. 12-24 additional subjects will be treated at the selected dose level. No staggered dosing required.

Biological: C-CAR168

Interventions

C-CAR168 BIOLOGICAL

This is a multi-center, Phase 1/2, open-label, dose-escalation and dose-expansion study evaluating C-CAR168 for the treatment of autoimmune diseases refractory to standard therapy. A traditional 3+3 design is used to identify the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) in disease-specific cohorts.

Arm 1: Dose Level -1 (DL-1); Arm 2: Dose Level 1 (DL1); Arm 3: Dose Level 2 (DL2); Arm 4: Dose Level 3 (DL3); Arm 5: Dose Expansion Cohort

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent: Voluntary signed consent required.
• Age \& Gender: Males and females, 18-70 years old.
• Diagnosis: Clinical diagnosis of SLE per EULAR/ACR criteria for at least 6 months.
• Lupus Nephritis (LN): Biopsy-confirmed active proliferative LN (Class III/IV ± V) within the past 12 months.
• Refractory Disease:
• Treated with at least two immunosuppressants for ≥8 weeks.
• Stable but active disease despite standard therapy (steroids, IS, monoclonal antibodies).
• Steroid dose ≤30 mg/day (if applicable).
• Disease Activity at Screening:
• SLE without LN: SLEDAI-2K ≥8 and 1 BILAG A or 2 BILAG B scores.
• LN Patients: Proteinuria ≥1.0 g/day or UPCR ≥1.0 g/g.
• Autoantibody Status:
• o Positive ANA (≥1:80), anti-dsDNA (≥30 IU/mL), and/or anti-Smith antibody.
• Infection Status: No active infection within 2 weeks before leukapheresis.
• Life Expectancy: Greater than 6 months.

You may not qualify if:

• Any other concomitant diseases requiring long term systemic steroids (oral or intravenously) treatment that may confound the interpretation of study results or have interference with background steroid tapering for the subjects.
• Any of the following:
• Positive for Hepatitis B surface antigen (HBsAg)/core antibody (HBcAb)/e antibody (HBeAb)/e antigen (HBeAg).
• Positive for Hepatitis C Virus (HCV) antibodies.
• Positive for Human Immunodeficiency Virus (HIV) antibodies.
• Positive for syphilis antigen or antibody.
• Have an uncontrolled active infection.
• History of major organ transplantation (such as heart, lung, liver, kidney) or history of bone marrow/hematopoietic stem cell transplantation.
• History of any of stroke, unstable angina, myocardial infarction, congestive heart failure (NYHA Class III or IV), severe cardiomyopathy or ventricular arrhythmia requiring medication or mechanical control within 6 months of screening.
• History of ≥ Grade 2 bleeding within the past 30 days.
• Received a live vaccine within 4 weeks prior to signing the ICF.
• Received any of the following treatments:
• Prednisone treatment of ≥ 100 mg/d or equivalent corticosteroid therapy for ≥14 days within the previous 8 weeks.
• Receive plasma exchange, plasma separation, hemodialysis, or intravenous injection of immunoglobulin (IVIG) within 14 days prior to leukapheresis.
• Use of any other investigational clinical study drug within 28 days prior to leukapheresis. However, if the subject is not responsive to the treatment or have progressed and at least 3 half-lives have passed before the leukapheresis, he/she could be enrolled.

Sponsors & Collaborators

• AbelZeta Inc.: lead

Study Sites (1)

AbelZeta, Inc.

Rockville, Maryland, 20850, United States

Location

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Scott Antonia

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yihong Yao, PhD

CONTACT

301-785-6047; clinicaltrials@abelzeta.com

Nurat Quadri, MS

CONTACT

2405525870; clinicaltrials@abelzeta.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study uses a 3+3 dose escalation design to determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of C-CAR168. Subjects in each dose level will be enrolled sequentially with a minimum 28-day interval between infusions. Upon completion of dose escalation, 12-24 additional subjects may be enrolled in a dose expansion phase, pending Safety Review Committee (SRC) approval. No staggering is required during the expansion phase.

Study Record Dates

• First Submitted: March 26, 2025
• First Posted: April 20, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: February 3, 2026

Record last verified: 2026-02

Locations

US (1)