Relmacabtagene Autoleucel for the Treatment of Systemic Sclerosis

NCT06414135 | Recruiting Phase 1 DMC

• 1 other identifier: JWCAR029029
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Relma-cel is a product containing CD19-CAR-transduced T cells. The purpose of this study is to evaluate the safety of Relma-cel at different dose levels in patients with early diffuse systemic sclerosis. Efficacy will be explored too. If enrolled, participants will undergo leukapheresis, lymphodepleting chemotherapy and administration of Relma-cel.

Conditions

Systemic Sclerosis

Keywords

CAR-T cell therapy; systemic sclerosis; B cell depletion

Outcome Measures

Primary Outcomes (2)

• DLT rate

  the incidence of dose-limiting toxicity

  28 days

• Occurrence of AEs and SAEs

  frequency and severity of AEs and SAEs

  3 months

Secondary Outcomes (16)

• Relma-cel cell numbers and transgene copy numbers and duration in blood

  baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration

• the changes of CD19+ cells and other B cell subsets

  baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration

• the change from baseline in Composite Response Index in Systemic Sclerosis (CRISS)

  baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration

• the change from baseline in Sclerodema Clinical Trial Consortium-Damage Index (SCTC-DI)

  baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration

• the change from baseline in modified Rodnan Skin Score (mRSS)

  baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration

Study Arms (1)

Relma-cel arm

EXPERIMENTAL

All participants will receive Relma-cel once at different dose levels

Biological: Relma-cel

Interventions

Relma-cel BIOLOGICAL

All participants will receive Relma-cel once at different dose levels: 25×10\^6 CAR+ T cells、50×10\^6 CAR+ T cells、75×10\^6 CAR+ T cells

Relma-cel arm

Eligibility Criteria

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

You may qualify if:

• 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:
• 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;
• progressive: having below manifestations within 6 months
• mRSS increases by \>= 3
• 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:
• Renal function: CrCl ≥50 ml/min (Cockcroft/Gault equation)
• 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.
• 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)
• Coagulation: INR ≤ 1.5 x ULN, PT ≤1.5 x ULN

You may not qualify if:

• 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

Sponsors & Collaborators

• Liangjing Lu: lead
• Shanghai Ming Ju Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, 200001, China

RECRUITING

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

relmacabtagene autoleucel

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Liangjing Lu

  RenJi Hospital

  STUDY CHAIR

Central Study Contacts

Liangjing Lu

CONTACT

86-13661472001; Lu_liangjing@163.com

medical JW

CONTACT

+86 21 50464201; Relma-celMedical@jwtherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 6, 2024
• First Posted: May 16, 2024
• Study Start: June 12, 2024
• Primary Completion: May 1, 2025
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 15, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)