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

Primary Purpose

Systemic Lupus Erythematosus

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Relma-cel
Sponsored by
Shanghai Ming Ju Biotechnology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring Relma-cel, Systemic lupus erythematosus, CD19-CART

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Sign an informed consent form (ICF) voluntarily. At the time of signing the ICF, you must be between 18 and 70 years old (inclusive), male or female. A diagnosis of SLE according to the 1997 revised criteria of the American College of Rheumatology (ACR). 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: Prednisone (or equivalent) ≥7.5 mg/ day, and ≤30 mg/ day. There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants. 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: 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. 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. 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. Combined with other autoimmune diseases, systematic treatment is needed. History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation. IgA deficiency was present during screening (serum IgA level < 10 mg/dL)

Sites / Locations

  • Relma-cel MedicalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Relma-cel be administrated in four dose level

Arm Description

Outcomes

Primary Outcome Measures

DLT rate
The incidence of dose-limiting toxicity
determine RP2D
To determine RP2D(Phase 2 recommended dose)

Secondary Outcome Measures

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
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
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
Autoantibody detection
Autoantibody detection up to 3 months after CD19 cCAR T cells infusion

Full Information

First Posted
February 6, 2023
Last Updated
March 12, 2023
Sponsor
Shanghai Ming Ju Biotechnology Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05765006
Brief Title
CD19-CART(Relma-cel) for Moderate to Severe Active Systemic Lupus Erythematosus
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 24, 2023 (Actual)
Primary Completion Date
December 30, 2024 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Ming Ju Biotechnology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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 .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus
Keywords
Relma-cel, Systemic lupus erythematosus, CD19-CART

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Relma-cel be administrated in four dose level
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Relma-cel
Intervention Description
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
Primary Outcome Measure Information:
Title
DLT rate
Description
The incidence of dose-limiting toxicity
Time Frame
3 months
Title
determine RP2D
Description
To determine RP2D(Phase 2 recommended dose)
Time Frame
3 months
Secondary Outcome Measure Information:
Title
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.
Description
SELENA-SLEDAI score taken up to 3 months after CD19 cCAR T cells infusion
Time Frame
3 months
Title
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.
Description
BILAG-2004 level taken up to 3 months after CD19 cCAR T cells infusion
Time Frame
3 months
Title
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.
Description
PGA score taken up to 3 months after CD19 cCAR T cells infusion
Time Frame
3 months
Title
Autoantibody detection
Description
Autoantibody detection up to 3 months after CD19 cCAR T cells infusion
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Sign an informed consent form (ICF) voluntarily. At the time of signing the ICF, you must be between 18 and 70 years old (inclusive), male or female. A diagnosis of SLE according to the 1997 revised criteria of the American College of Rheumatology (ACR). 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: Prednisone (or equivalent) ≥7.5 mg/ day, and ≤30 mg/ day. There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants. 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: 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. 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. 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. Combined with other autoimmune diseases, systematic treatment is needed. History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation. IgA deficiency was present during screening (serum IgA level < 10 mg/dL)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
medical JW
Phone
+86 21 50464201
Email
Relma-celMedical@jwtherapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
yu Hu
Organizational Affiliation
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
heng Mei
Organizational Affiliation
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
liangjing Lv
Organizational Affiliation
Renji Hospital Shanghai Jiaotong University School of Medical
Official's Role
Principal Investigator
Facility Information:
Facility Name
Relma-cel Medical
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
medical Relma-cel
First Name & Middle Initial & Last Name & Degree
chunli Mei
First Name & Middle Initial & Last Name & Degree
heng Mei
First Name & Middle Initial & Last Name & Degree
liangjing Lv

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
3005930
Citation
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.
Results Reference
result

Learn more about this trial

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

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