C-CAR168, an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy, in Participants With Systemic Sclerosis (SSc) Refractory to Standard Therapy

A Multi-center, Phase 1b Clinical Study of an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy (C-CAR168) for the Treatment of Systemic Sclerosis (SSc) Refractory to Standard Therapy

This Phase 1b, 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 Systemic Sclerosis (SSc) who are not responding to standard therapy. Approximately 6-12 participants will undergo leukapheresis, lymphodepletion with fludarabine and cyclophosphamide, and infusion of C-CAR168. Participants will be followed for 24 months (2 years) to evaluate safety, CAR T-cell persistence, pharmacokinetics/pharmacodynamics, biomarkers, and preliminary efficacy results. 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 Sclerosis; Systemic Sclerosis (SSc); Systemic Sclerosis Pulmonary; Systemic Sclerosis With Lung Involvement; Systemic Sclerosis (Scleroderma); Systemic Sclerosis - 2013 ACR/EULAR Classification Criteria
• Intervention / Treatment: Biological: C-CAR168

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kirstin Liechty, Head of Clinical Operations, PhD; Phone Number: 267-566-6081; Email: kirstin.liechty@abelzeta.com
• Study Contact Backup: Name: Yihong Liechty, Head of Clinical Operations, PhD; Phone Number: 267-566-6081; Email: kirstin.liechty@abelzeta.com

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Able to sign and date the Informed Consent Form (ICF).

2. Female or male, aged 18-70 years (inclusive) with body weight ≥40 kg.

3. Have a clinical diagnosis of diffuse cutaneous SSc according to the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification.

4. Disease duration between the onset of the first non-Raynaud's sign/symptom and ICF signing shall be ≤ 6 years.

5. SSc Disease Activity meet all following criteria:

   1. Modified Rodnan Skin Score (mRSS) ≥15.
   2. Chest High Resolution Computed Tomography (HRCT) shows SSc related ground-glass opacities.
   3. Percent predicted forced vital capacity (ppFVC)<70% or precent predicted (diffusing capacity of the lungs for carbon monoxide) ppDLco<70%.

6. Positivity for at least one SSc-specific autoantibodies:

   1. anti-Scl70 antibody.
   2. anti-RNA polymerase III antibody.
   3. anti-centromere antibody.
   4. anti-Th/To antibody.
   5. and anti-U3RNP antibody.

7. Refractory to at least two prior standard-of-care regimens, including immunosuppressives and/or a biologic note: "Refractory" is defined as receiving each listed drug for ≥6 months with either no response, disease progression after transient remission, or persistent disease progression on treatment.

8. Ability to taper steroids to protocol allowed doses

Exclusion Criteria:

1. ppFVC<45% or ppDLco <40%.

2. Severe pulmonary arterial hypertension (PAH) as measured by screening echocardiogram (ECHO), or had documented mean positive airway pressure PAP (mPAP) > 45mmHg on recent right heart catheterization (RHC).

   Note: RHC is not mandatory at screening, however participant with high-risk ECHO findings warrant close clinical vigilance, and participant with mPAP> 45mmHg at baseline shall not proceed with lymphodepletion.

3. Presence of clinically significant abnormalities on chest high-resolution computed tomography (HRCT) that are UNRELATED to SSc.

4. Cutaneous sclerosis that impedes venous access required for leukapheresis, lymphodepletion, C-CAR168 infusion, other study procedures and emergency rescue interventions.

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	Biological: C-CAR168; Autologous anti-CD20/BCMA chimeric antigen receptor T-cell therapy administered as a single intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of treatment-emergent adverse events	Incidence and severity of treatment-emergent adverse events, serious adverse events, dose-limiting toxicities, CRS, ICANS, adverse events of special interest, and treatment- or procedure-related adverse events.	Through Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Achieving Response	Proportion of participants achieving a response per the revised Composite Response Index for Systemic Sclerosis (r-CRISS)	Through Month 24
Pharmacokinetics of C-CAR168 Utilizing Flow Cytometry	Characterize T-cell expansion and persistence utilizing flow cytometry	Through Month 24
Pharmacokinetics of C-CAR168 measured by quantitative polymerase chain reaction (qPCR)	Characterize CAR T-cell expansion and persistence using qPCR	Through Month 24
Proportion of Participants Progressed	Proportion of participants that progress meeting any of the protocol defined progression criteria	Through Month 24
Time to First Response	Time to participant meeting first response as defined in the protocol	Through Month 24
Duration of Response (DOR)	Time of response from first response until progression as defined in the protocol	Through 24 months

Collaborators and Investigators

• Sponsor: AbelZeta Inc.
• Investigators: Study Director: Yihong Yao, PhD, AbelZeta Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: September 27, 2026
• First Submitted That Met QC Criteria: September 27, 2026
• First Posted (Actual): October 2, 2026

Study Record Updates

• Last Update Posted (Actual): October 13, 2026
• Last Update Submitted That Met QC Criteria: October 7, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: CAR-T; Systemic Sclerosis; CD20; Autoimmune disease; BCMA; Autoimmune; CAR-T Therapy; Chimeric Antigen Receptor T cell; SSc; CAR T-cell Therapy; chimeric antigen receptor T-cell Therapy
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: ABZT-413

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