## Protocol Section
### Identification Module
**NCT ID:** NCT06414135

**Brief Title:** Relmacabtagene Autoleucel for the Treatment of Systemic Sclerosis

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

#### Organization Study ID Info
**ID:** JWCAR029029
#### Organization
**Class:** OTHER
**Full Name:** RenJi Hospital
### Status Module
#### Completion Date
**Date:** 2027-04

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-09

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-05

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-06
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Shanghai Ming Ju Biotechnology Co., Ltd.

#### Lead Sponsor

**Class:** OTHER

**Name:** Liangjing Lu

#### Responsible Party

**Investigator Affiliation:** RenJi Hospital

**Investigator Full Name:** Liangjing Lu

**Investigator Title:** Professor

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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 Module

**Conditions:**

- Systemic Sclerosis

**Keywords:**

- CAR-T cell therapy

- systemic sclerosis

- B cell depletion

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 6

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Biological: Relma-cel

**Label:** Relma-cel arm

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Relma-cel arm

**Description:** 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

**Name:** Relma-cel

**Type:** BIOLOGICAL

### Outcomes Module

#### Primary Outcomes

**Description:** the incidence of dose-limiting toxicity

**Measure:** DLT rate

**Time Frame:** 28 days

**Description:** frequency and severity of AEs and SAEs

**Measure:** Occurrence of AEs and SAEs

**Time Frame:** 3 months

#### Secondary Outcomes

**Description:** Normally Relma-cel number and transgene copy number will gradually decrease to non-measurable as time goes on.

**Measure:** 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

**Description:** 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

**Measure:** 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

**Description:** 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.

**Measure:** 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

**Description:** 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.

**Measure:** 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

**Description:** 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.

**Measure:** 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

**Description:** The two items are used to evaluate pulmonary function. Normally both indicators should be greater than 80%.

**Measure:** 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

**Description:** LVEF is an indicator of the heart's ability to eject blood out. The normal range is 50-55%

**Measure:** 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

**Description:** 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.

**Measure:** 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

**Description:** 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

**Measure:** 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

**Description:** 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.

**Measure:** 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

**Description:** Normally all the antibodies are negative in human body. A positive result means abnormalities of immune system.

**Measure:** 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

**Description:** 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.

**Measure:** 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

**Description:** 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

**Measure:** the change from baseline in nailfold capillaroscopy examination, e.g., the capillary density, the diameter of capillaries

**Time Frame:** 12 months

**Description:** the thickness of epiderm and dermis will be thinner in the presence of systemic sclerosis.

**Measure:** the change from baseline in skin stiffness (measuring the thickness of epiderm and dermis) by skin ultrasound

**Time Frame:** 12 months

**Description:** 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.

**Measure:** the change from baseline in health assessment questionnaire -damage index (HAQ-DI)

**Time Frame:** 12 months

**Description:** with Relma-cel administration, IgG, IgM, IgE, IgA will significantly decrease, then graduallly increase as the effect of Relma-cel disappears

**Measure:** 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

### Eligibility Module

**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
* 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

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Lu_liangjing@163.com

**Name:** Liangjing Lu

**Phone:** 86-13661472001

**Role:** CONTACT

**Contact 2:**

**Email:** Relma-celMedical@jwtherapeutics.com

**Name:** medical JW

**Phone:** +86 21 50464201

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Email:** Lu_liangjing@163.com

- **Name:** Liangjing Lu

- **Phone:** 86-13661472001

- **Role:** CONTACT

**Country:** China

**Facility:** Renji Hospital, Shanghai Jiaotong University School of Medicine

**Zip:** 200001

#### Overall Officials

**Official 1:**

**Affiliation:** RenJi Hospital

**Name:** Liangjing Lu

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000003240

- Term: Connective Tissue Diseases

- ID: D000012871

- Term: Skin Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M15415

- Name: Sclerosis

- Relevance: HIGH

- As Found: Sclerosis

- ID: M15412

- Name: Scleroderma, Systemic

- Relevance: HIGH

- As Found: Systemic Sclerosis

- ID: M25560

- Name: Scleroderma, Diffuse

- Relevance: HIGH

- As Found: Systemic Sclerosis

- ID: M6464

- Name: Connective Tissue Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T5565

- Name: Systemic Scleroderma

- Relevance: HIGH

- As Found: Systemic Sclerosis

- ID: T1861

- Name: Diffuse Cutaneous Systemic Sclerosis

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000012595

- Term: Scleroderma, Systemic

- ID: D000045743

- Term: Scleroderma, Diffuse

- ID: D000012598

- Term: Sclerosis

### Misc Info Module

- Version Holder: 2024-05-31
