Relmacabtagene Autoleucel for the Treatment of Systemic Sclerosis

May 9, 2024 updated by: Liangjing Lu

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Shanghai, China, 200001
        • Renji Hospital, Shanghai Jiaotong University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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
  • diagnosed with systemic sclerosis associated interstitial lung disease, defined as ground glass opacity on HRCT; and 55% ≤FVC<70% or 55%≤DLCO <70%

  • 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 > 10%
      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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Relma-cel arm
All participants will receive Relma-cel once at different dose levels
Biological: Relma-cel
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DLT rate
Time Frame: 28 days
the incidence of dose-limiting toxicity
28 days
Occurrence of AEs and SAEs
Time Frame: 3 months
frequency and severity of AEs and SAEs
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relma-cel cell numbers and transgene copy numbers and duration in blood
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
Normally Relma-cel number and transgene copy number will gradually decrease to non-measurable as time goes on.
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
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
Theoretically the number of CD19+ cells and other B cell subsets will significantly decreased following Relma-cel administration and gradually increase to normal level as the effect of Relma-cel disappear
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)
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
Criss is an indicator to evaluate the efficacy of systemic sclerosis therapies. A score greater than or equal to 0.6 means Improvement. A score less than 0.6 means No Improvement.
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)
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
SCTC-DI is a 23-item questionnaire to evaluate the organ damage in patients with systemic sclerosis. The range is between 0-55. The higher the score is, the worse the damage is.
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)
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
mRSS is an instrument to evaluate cutaneous involvement in patients with systemic sclerosis. The total score ranges from 0 to 51. The higher the score is, the more the cutaneous involvement is.
baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in pulmonary function (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO))
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
The two items are used to evaluate pulmonary function. Normally both indicators should be greater than 80%.
baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in cardiac function (left ventricular ejection fraction, LVEF)
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
LVEF is an indicator of the heart's ability to eject blood out. The normal range is 50-55%
baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in high resolution computed tomography (HRCT)
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
HRCT is a radiology test of the lungs. In this trial, HRCT will be used to evaluate the lesion size of the lungs, e.g., a lesion could be 10% of the lungs. The greater the percentage is, the worse the lesion is.
baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in disease activity score -28 (DAS-28) if any joint involvement
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
DAS-28 is a questionnaire to evaluate disease activity in patients with rheumatoid arthritis. 28 joints will be evaluated. Less than 2.6 means the disease is in remission. 2.6-3.2 means a low disease activity. More than 3.2 means active disease needing change in medication. More than 5.1 means very active disease that requires careful monitoring and adjustment to medication
baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in the levels of inflammation biomarkers including C-reactive protein (CRP), erythropoietin sedimentation rate (ESR) and ferritin
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
CRP, ESR and ferritin are inflammation biomarkers. The normal ranges are different in different labs. Higher values than the upper limit of normal range mean the presence of inflammation.
baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
systemic sclerosis specific antibodies, e.g., anti-scl-70 antibodies, anti-RNA polymerase III antibodies, anti-centrosome antibodies, antinuclear antibody (ANA)
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
Normally all the antibodies are negative in human body. A positive result means abnormalities of immune system.
baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in skin biopsy pathology, e.g., the number of lymphocytes, the thickness of epiderm
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
In the presence of systemic sclerosis, the increased number of T and B lymphocytes, the thinning of epiderm and the decreased number of sweat gland are expected.
baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
the change from baseline in nailfold capillaroscopy examination, e.g., the capillary density, the diameter of capillaries
Time Frame: 12 months
nailfold capillaroscopy is a device to observe the capillaries in the nailfold areas. With system sclerosis, the capillary density will diminish and expanded capillary loop may occur
12 months
the change from baseline in skin stiffness (measuring the thickness of epiderm and dermis) by skin ultrasound
Time Frame: 12 months
the thickness of epiderm and dermis will be thinner in the presence of systemic sclerosis.
12 months
the change from baseline in health assessment questionnaire -damage index (HAQ-DI)
Time Frame: 12 months
HAQ-DI, assesses a patient's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each item asks over the past week "Are you able to …" perform a particular task. The patient's responses are made on a scale from zero (no disability) to three (completely disabled). The total score will be 0-3. The higher the score is, the worse the body function is.
12 months
the change from baseline in IgG, IgM, IgE, IgA
Time Frame: baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration
with Relma-cel administration, IgG, IgM, IgE, IgA will significantly decrease, then graduallly increase as the effect of Relma-cel disappears
baseline prior to Relma-cel administration, then through study completion, an average of 2 years after Relma-cel administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Liangjing Lu

Collaborators

Shanghai Ming Ju Biotechnology Co., Ltd.

Investigators

  • Study Chair: Liangjing Lu, RenJi Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2024

Primary Completion (Estimated)

May 1, 2025

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

May 6, 2024

First Submitted That Met QC Criteria

May 9, 2024

First Posted (Actual)

May 16, 2024

Study Record Updates

Last Update Posted (Actual)

May 16, 2024

Last Update Submitted That Met QC Criteria

May 9, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JWCAR029029

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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