CD19-CART(Relma-cel) for Moderate to Severe Active Systemic Lupus Erythematosus

A Phase I Dose-escalation Study Evaluate the Safety Tolerability Pharmacokinetics(PK) and Pharmacodynamics(PD) of Relma-cel in Subjects With Moderate to Severe Active Systemic Lupus Erythematosus (SLE)

This is a phase I, open-label, single-arm, multicenter study to asess the safety tolerability pharmacokinetics and pharmacodynamics of Relma-cel in moderate or severe active systemic lupus erythematosus (SLE) subjects in China.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: Relma-cel

Detailed Description

This is a phase I, open-label, single-arm, multicenter study to asess the safety tolerability pharmacokinetics(PK) and pharmacodynamics(PD) of Relma-cel in moderate or severe active systemic lupus erythematosus (SLE) subjects in China.

There will be 4 dose level (15x106 CAR+ T cells as the back up dose ,25x106 CAR+ T cells as the starting dose 、50x106 CAR+ T cells and 100x106(or 150 x106CAR+ T cells）Dose escalation, to evaluate the safety、 tolerability of Relma-cel in adult subjects of SLE and determine RP2D .

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: medical JW; Phone Number: +86 21 50464201; Email: Relma-celMedical@jwtherapeutics.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Relma-cel Medical
    • Contact: medical Relma-cel
    • Principal Investigator: chunli Mei
    • Principal Investigator: Heng Mei
    • Principal Investigator: liangjing Lv

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Sign an informed consent form (ICF) voluntarily.
2. At the time of signing the ICF, you must be between 18 and 70 years old (inclusive), male or female.
3. A diagnosis of SLE according to the 1997 revised criteria of the American College of Rheumatology (ACR).
4. The history of SLE prior to screening was at least 6 months, and the disease remained active at least 2 months after the use of a stable standard SLE regimen prior to screening.

Standard treatment regimen refers to the steady use of any of the following (alone or in combination) : corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), and other immunosuppressants or immunomodulators including azathioprine, Mycophenolate Mofetil, cyclophosphamide, methotrexate, leflunomide, tacrolimus, and cyclosporine.

Oral corticosteroids must meet the following requirements:

1. Prednisone (or equivalent) ≥7.5 mg/ day, and ≤30 mg/ day.
2. There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants.
3. At least 8 weeks of treatment prior to screening, and the dose must be kept stable for > 2 weeks.

5. Screening is positive for antinuclear antibodies, and/or anti-DS-DNA antibodies, and/or anti-Smith antibodies.

6. SELENA-SLEDAI score ≥8 during the screening period. Score ≥6 for SELENA-SLEDAI clinical symptoms (except for low complement and/or anti-DS-DNA antibodies) if low complement and/or anti-DS-DNA antibody score is present.

Exclusion Criteria:

1. Severe lupus nephritis (defined as proteinuria > 6 g/24h or serum creatinine > 2.5 mg/dL or 221 μmol/L), treatment with active nephritis with Prohibited drugs, hemodialysis, or prednisone ≥100 within 8 weeks prior to screening mg/d or equivalent glucocorticoid therapy ≥14 days.
2. Prior to screening, other lupus crises, such as active central nervous system lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe agranulocytosis, severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, and severe vasculitis.
3. Clinically significant central nervous system diseases or pathological changes not caused by lupus prior to screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, convulsions/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
4. Combined with other autoimmune diseases, systematic treatment is needed.
5. History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
6. IgA deficiency was present during screening (serum IgA level < 10 mg/dL)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relma-cel be administrated in four dose level	Biological: Relma-cel; CD19-targeted Chimeric AntigenReceptor (CAR) T Cells; Relma-cel be administrated at four dose level:25×106 CAR+ T cells、50×106 CAR+ T cells、100×106 CAR+ T cells/150×106 CAR+ T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT rate	The incidence of dose-limiting toxicity	3 months
determine RP2D	To determine RP2D(Phase 2 recommended dose)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autoantibody detection	Autoantibody detection up to 3 months after CD19 cCAR T cells infusion	3 months
SELENA-SLEDAI （Safety of Estrogens in Systemic Lupus Erythematosus National Assessment） score； 0 to 4 is basically no disease activity; 5 to 9 is light activity; 10 to 14 is moderate activity;≥15 is considered heavy activity.	SELENA-SLEDAI score taken up to 3 months after CD19 cCAR T cells infusion	3 months
BILAG -2004（updated version of british isles lupus assessment group ） level；The BILAG 2004 index categorizes disease activity into 5 different levels from A-E.Grade A represents very active disease.	BILAG-2004 level taken up to 3 months after CD19 cCAR T cells infusion	3 months
PGA (physician global assessment) score,The PGA scale ranges from "no disease activity" (0) to the "most severe disease activity" (3).the score is between 0 to 3.	PGA score taken up to 3 months after CD19 cCAR T cells infusion	3 months

Collaborators and Investigators

• Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
• Investigators: Principal Investigator: yu Hu, Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology; Principal Investigator: heng Mei, Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology; Principal Investigator: liangjing Lv, Renji Hospital Shanghai Jiaotong University School of Medical

Publications and helpful links

General Publications

• Kaufman JL, Deak ST, Erdman W. Radionuclide scans to define patterns of occult myonecrosis. N J Med. 1986 Feb;83(2):101-3. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2023
• Primary Completion (Anticipated): December 30, 2024
• Study Completion (Anticipated): December 30, 2025

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 28, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 12, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Systemic lupus erythematosus; CD19-CART; Relma-cel
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: JWCAR029012

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