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.
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.
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).
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.
Single group
C-CAR168
Biological/VaccineAutologous 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).
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.
Proportion of Participants Achieving Response
Proportion of participants achieving a response per the revised Composite Response Index for Systemic Sclerosis (r-CRISS)
Pharmacokinetics of C-CAR168 Utilizing Flow Cytometry
Characterize T-cell expansion and persistence utilizing flow cytometry
Pharmacokinetics of C-CAR168 measured by quantitative polymerase chain reaction (qPCR)
Characterize CAR T-cell expansion and persistence using qPCR
Proportion of Participants Progressed
Proportion of participants that progress meeting any of the protocol defined progression criteria
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