Relma-cel for Moderate to Severe Active Systemic Lupus Erythematosus

NCT06297408 | Not Yet Recruiting Phase 1

• 1 other identifier: JWCAR029115
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

To assess the safety tolerability pharmacokinetics and pharmacodynamics of Relma-cel in moderate or severe active systemic lupus erythematosus (SLE) subjects in China.

Conditions

Systemic Lupus Erythematosus

Keywords

CD19-CART

Outcome Measures

Primary Outcomes (2)

• DLT rate

  The incidence of dose-limiting toxicity

  6months

• determine RP2D

  To determine RP2D(Phase 2 recommended dose)

  6months

Secondary Outcomes (3)

• SELENA-SLEDAI

  3 months after CD19 cCAR T cells infusion

• BILAG -2004

  3 months after CD19 cCAR T cells infusion

• PGA (physician global assessment) score

  3 months after CD19 cCAR T cells infusion

Study Arms (1)

Relma-cel

EXPERIMENTAL

Evaluate the safety and tolerability of Relma-cel in moderate to severe active systemic lupus erythematosus (SLE) and determine the Phase II Recommended Dose (RP2D)

Drug: Relma-cel

Interventions

Relma-cel DRUG

CD19-targeted Chimeric AntigenReceptor (CAR) T Cells

Also known as: if necessary can add other anti-SLE treatment such as corticosteroids, immunosuppressants, biologics

Relma-cel

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily signed an informed consent form (ICF).
• Applicants must be between 18 and 70 years old (inclusive) at the time of signing the ICF, male or female.
• Diagnosed with SLE according to the 2012 SLICC or 2019 EULAR/ACR version of the revised criteria.
• Disease remaining active after receiving corticosteroids combined immunosuppressive therapy and/or biological agents, with a stable treatment plan for at least 2 months and a stable dose for at least 2 weeks before screening.
• Oral corticosteroids must meet the following requirements:
• Prednisone (or equivalent) ≥7.5 mg/day and ≤60 mg/day.
• When used in combination with immunosuppressants, there is no minimum daily dose requirement for corticosteroids.
• \. Positive antinuclear antibody, and/or anti-dsDNA antibody, and/or anti-Smith antibody at screening.
• \. SELENA-2k score ≥7 points during the screening period. 7. Active organ involvement during screening period. 8. No active infection (e.g., pneumonia, tuberculosis) within 2 weeks prior to screening period.
• \. Vascular access is sufficient for leukapheresis. 10. Adequate organ function:
• Renal function: defined as creatinine clearance (Cockcroft-Gault) ≥40 mL/min calculated without hydration assistance.
• Bone marrow function: defined as absolute neutrophil count (ANC) ≥1000 /μL, absolute lymphocyte count (ALC) ≥100 /μL, hemoglobin (Hb) ≥60 g/L, platelet count (PLT) ≥20,000 /μL. Blood transfusions and CSF must not be used to meet these requirements during the 7 days prior to eligibility screening.
• Liver function: defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN, total bilirubin \< 2.0 mg/dL (total bilirubin \< 3.0 mg/dL in subjects with Gilbert syndrome, except for caused by SLE).
• Coagulation function: defined as international ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5×ULN.
• Lung function: defined as ≤CTCAE grade 1 dyspnea and blood oxygen saturation (SpO2) ≥92% in indoor air (measured by pulse oximeter).

You may not qualify if:

• Severe lupus nephritis within 2 months before screening requires hemodialysis, or treatment with prednisone(or equivalent hormone) ≥100 mg/d for more than 14 days.
• Suffering from lupus crisis within 1 months before screening, assessed by the researcher as unsuitable for participation in this study.
• 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. Central nervous system manifestations caused by lupus before screening, including but not limited to lupus headache, epileptic seizures, cognitive impairment, impaired intellectual function, visual impairment, etc.
• Combined with other autoimmune diseases, systemic treatment is required.
• History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
• When screening:
• \) Hepatitis C or human immunodeficiency virus (HIV) or syphilis infection. 7. A history of any of the following cardiovascular diseases in the 6 months prior to screening: Class III or IV heart failure as defined by the New York Heart Association (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmia, any ventricular arrhythmia, or other clinically significant heart disease.
• \. Use any other clinical study drugs within 1 month before screening. However, if the research treatment is ineffective or the disease relapses, and at least 3 half-life period have been passed before screening, enrollment is allowed.
• \. Previously received CAR-T cell or other genetically modified T cell therapies.
• \. There was a history of ≥grade 2 bleeding within 30 days prior to screening, or long-term treatment with anticoagulants (such as warfarin, low molecular weight heparin, or factor Xa inhibitors).
• \. Plasma exchange, plasma separation or hemodialysis were performed within 14 days before leukapheresis.
• \. Use any live vaccine against infectious diseases within 1 month prior to screening.
• \. Known life-threatening allergic reactions, hypersensitivities, or intolerances to Relma-cel or their excipients, including DMSO.
• \. A history or evidence of suicidal thoughts in the 6 months before signing the ICF, or any suicidal behavior in the 12 months prior, or is considered by the investigator there is a significant risk of suicide.
• \. Malignant tumor within 2 years before signing the ICF. Exceptions include non-melanoma skin cancer after radical treatment, localized prostate cancer, biopsy-confirmed cervical carcinoma in situ or squamous intraepithelial lesions detected by cervical smear, and completely resected breast carcinoma in situ.

Sponsors & Collaborators

• Shanghai Ming Ju Biotechnology Co., Ltd.: lead

Related Publications (1)

• Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.

  PMID: 36109639 RESULT

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

relmacabtagene autoleucel; Adrenal Cortex Hormones; Immunosuppressive Agents; Biological Products

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Complex Mixtures

Study Officials

• xiaofeng zeng

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

JW Medical

CONTACT

021-50464201; Relma-celMedical@jwtherapeutics.com

Yue Dong

CONTACT

01069154127; dongyue@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 7, 2024
• Study Start: March 1, 2024
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2026
• Last Updated: March 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share