CAR-T cell therapy for systemic sclerosis treatment

A Dose Ranging Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Pharmacodynamics of Relmacabtagene Autoleucel (Relma-cel) in Patients With Refractory/Progressive Systemic Sclerosis

This study is testing a new CAR-T cell therapy to see if it can help people with early diffuse systemic sclerosis who haven't found relief with other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: RenJi Hospital (Academic / other)
• Drugs / interventions: rituximab, belimumab, tocilizumab, CAR-T, methotrexate, cyclophosphamide, prednisone, chemotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT06414135 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of Relmacabtagene Autoleucel (Relma-cel), a CAR-T cell therapy targeting CD19, in patients with early diffuse systemic sclerosis. Participants will undergo leukapheresis to collect T cells, followed by lymphodepleting chemotherapy and administration of Relma-cel at varying dose levels. The study aims to determine the optimal dosing and assess the treatment's impact on disease progression and symptoms. It is a Phase 1 interventional trial focusing on patients who have not responded to conventional therapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with a diagnosis of diffuse systemic sclerosis who have not responded to standard treatments.

Not a fit: Patients with active systemic infections or those outside the age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with refractory or progressive systemic sclerosis.

How similar studies have performed: While CAR-T cell therapy has shown promise in other conditions, this specific application for systemic sclerosis is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* voluntary to sign the ICF
* aged between 18-65 years old (inclusive)
* diagnosed with diffuse systemic sclerosis according to 2013 ACR Systemic Sclerosis Classification Criterion
* meet the definitions of refractory/progressive as below:

  1. refractory: non-respondent to or disease recurrence after remission with conventional therapies. Conventional therapies are defined as treated for more than 6 months with low dose steroids (≤ 15 mg prednisone equivalent), cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporin or biologics such as rituximab, belimumab, telitacicept, tocilizumab;
  2. progressive: having below manifestations within 6 months

     1. mRSS increases by \>= 3
     2. FVC decreases by \> 10% or FVC decreases by \> 5% and DLCO decreases by \> 15%
* without systemic active infections within 2 weeks of leukapheresis, e.g., infectious pneumonia, tuberculosis
* available vascular access for leukapheresis
* major organ functions:

  1. Renal function: CrCl ≥50 ml/min (Cockcroft/Gault equation)
  2. Bone marrow function: ANC ≥ 1000/uL, absolute lymphocyte count ≥100/uL, Hb ≥90 g/L, Platelet count ≥75 x 10\^9/L. Blood transfusion and infusion of growth factors within 7 days of eligibility assessment are not allowed.
  3. Liver function: ALT ≤ 3 x ULN, AST ≤ 3 x ULN, total bilirubin ≤ 2 x ULN (in case of Gilbert syndrome, total bilirubin ≤ 3 x ULN)
  4. Coagulation: INR ≤ 1.5 x ULN, PT ≤1.5 x ULN
  5. Cardiac function: LVEF ≥ 55%
* negative result of serum β-hCG measurement for women of childbearing potential at screening and within 48 hours of the first dose of lymphodepletion
* Female subjects with childbearing potential or male subjects with partners of childbearing potential should adopt medically effective contraception or abstinence from enrollment to 2 years after the end of the study; female subjects with childbearing potential should have a negative serum hCG test within 7 days of enrollment and not in lactation

Exclusion Criteria:

* NYHA class IV
* FVC predicted \< 45% or DLCO predicted \< 40%
* abnormalities on HRCT not attributable to systemic sclerosis
* history of autologous stem cell transplantation
* with manifestations of renal crisis
* with other autoimmune comorbidities that need systemic treatment
* with a history of severe drug allergy
* with congenital immunoglobulin deficiency
* with malignant tumors, except for nonmelanoma skin cancer, in situ cervical cancer, bladder cancer, breast cancer which has been disease free for more than 2 years
* with psychiatric diseases or severe cognition dysfunctions
* within 5 half-life cycles of the last administration of an investigational product
* pregnant, lactation or plan to be pregnant within one year
* a history of CAR-T therapy or other gene-modified T cell targeted therapies
* other conditions that are not suitable for enrollment of the study in the judgement of the investigator
* the use of any live vaccines against infections within one month of the screening
* with any manifestations of active tuberculosis at screening

Where this trial is running

Shanghai

• Renji Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Liangjing Lu

Conditions Systemic Sclerosis; CAR-T cell therapy; systemic sclerosis; B cell depletion