A Phase 1b Study of C-CAR168 in Participants With Systemic Sclerosis (SSc)

NCT07854483 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ABZT-413
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Systemic Sclerosis (SSc); Systemic Sclerosis; Systemic Sclerosis (Scleroderma); Systemic Sclerosis - 2013 ACR/EULAR Classification Criteria; Systemic Sclerosis Pulmonary; Systemic Sclerosis With Lung Involvement

Keywords

Autoimmune; CAR-T; CAR T-cell Therapy; Systemic Sclerosis; SSc; Autoimmune disease; CD20; BCMA; CAR-T Therapy; Chimeric Antigen Receptor T cell; chimeric antigen receptor T-cell Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Proportion of Participants Achieving Response

  Through Month 24

• Pharmacokinetics of C-CAR168 Utilizing Flow Cytometry

  Through Month 24

• Pharmacokinetics of C-CAR168 measured by quantitative polymerase chain reaction (qPCR)

  Through Month 24

• Proportion of Participants Progressed

  Through Month 24

• Time to First Response

  Through Month 24

Study Arms (1)

C-CAR168

EXPERIMENTAL

Participants will receive: • Leukapheresis • Fludarabine • Cyclophosphamide • Single intravenous infusion of C-CAR168

Biological: C-CAR168

Interventions

C-CAR168 BIOLOGICAL

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).

C-CAR168

Eligibility Criteria

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

You may qualify if:

• Able to sign and date the Informed Consent Form (ICF).
• Female or male, aged 18-70 years (inclusive) with body weight ≥40 kg.
• Have a clinical diagnosis of diffuse cutaneous SSc according to the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification.
• Disease duration between the onset of the first non-Raynaud's sign/symptom and ICF signing shall be ≤ 6 years.
• SSc Disease Activity meet all following criteria:
• Modified Rodnan Skin Score (mRSS) ≥15.
• Chest High Resolution Computed Tomography (HRCT) shows SSc related ground-glass opacities.
• Percent predicted forced vital capacity (ppFVC)\<70% or precent predicted (diffusing capacity of the lungs for carbon monoxide) ppDLco\<70%.
• Positivity for at least one SSc-specific autoantibodies:
• anti-Scl70 antibody.
• anti-RNA polymerase III antibody.
• anti-centromere antibody.
• anti-Th/To antibody.
• and anti-U3RNP antibody.
• 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.

You may not qualify if:

• ppFVC\<45% or ppDLco \<40%.
• 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.
• Presence of clinically significant abnormalities on chest high-resolution computed tomography (HRCT) that are UNRELATED to SSc.
• Cutaneous sclerosis that impedes venous access required for leukapheresis, lymphodepletion, C-CAR168 infusion, other study procedures and emergency rescue interventions.

Sponsors & Collaborators

• AbelZeta Inc.: lead

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Diffuse; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Immune System Diseases

Central Study Contacts

Kirstin Liechty, Head of Clinical Operations

CONTACT

267-566-6081; kirstin.liechty@abelzeta.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2026
• First Posted: October 2, 2026
• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share