Starting soon
Phase 1
C-CAR168, an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy, in Participants With Systemic Sclerosis (SSc) Refractory to Standard Therapy
Condition(s) studied
Systemic Sclerosis (SSc)Systemic SclerosisSystemic Sclerosis (Scleroderma)Systemic Sclerosis - 2013 ACR/EULAR Classification CriteriaSystemic Sclerosis PulmonarySystemic Sclerosis With Lung Involvement
Investigational drug(s) / intervention(s)
C-CAR168: Autologous anti-CD20/BCMA chimeric antigen receptor T-cell therapy administered as a single intravenous infusion
Study 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.
Eligibility
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.
Primary outcome measure(s)
- Incidence and severity of treatment-emergent adverse events — Through Month 24
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.
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Research Site |
Gilbert |
Arizona |
|
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