Clinical Study of ZM001 Injection in the Treatment of Refractory Systemic Lupus Erythematosus

NCT06852573 | Not Yet Recruiting Phase 1

• 1 other identifier: IM19SLE01
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open, single-arm, phase I clinical study of ZM001 in patients with refractory systemic lupus erythematosus

Conditions

Systemic Lupus Erythematosus

Keywords

ZM001 CD19 CAR-T; refractory systemic lupus erythematosus

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment Related adverse events (AEs)

  Incidence of adverse events associated with ZM001 reinfusion within 28 days of ZM001 reinfusion, type, frequency, and severity of abnormal clinically significant vital signs, electrocardiograms, and laboratory tests examined, including dose-limiting toxicity

  Up to 28 days after CAR-T cell infusion

Secondary Outcomes (22)

• Lupus Low Disease Activity State (LLDAS)

  Up to 24 week after CAR-T cell infusion

• disease remission (DORIS)

  Up to 24 week after CAR-T cell infusion

• SLEDAI-2K score

  Up to 24 week after CAR-T cell infusion

• British Isles Lupus Assessment Group Index (BILAG-2004)

  Up to 24 week after CAR-T cell infusion

• Clinician's general judgment (PGA)

  Up to 24 week after CAR-T cell infusion

Study Arms (1)

ZM001 Injection

EXPERIMENTAL

After preconditioning with chemotherapy, ZM001 Injection will be evaluated

Biological: ZM001 Injection

Interventions

ZM001 Injection BIOLOGICAL

ZM001 injection, 2.5× 10\^7 CAR-T cells, 5× 10\^7 CAR-T cells, 1× 10\^8 CAR-T cells and 2× 10\^8 CAR-T cells, treatment follows a lymphodepletion. Drug: Fludarabine Recommendation: 30 mg/m\^2 (D-5\~D-3), determined by tumor burden at baseline. Drug: Cyclophosphamide Recommendation: 300 mg/ m\^2 (D-5\~D-3), determined by tumor burden at baseline. Drug: Cyclophosphamide Recommendation: 300 mg/ m\^2 (D-5\~D-3), determined by tumor burden at baseline.

ZM001 Injection

Eligibility Criteria

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

You may qualify if:

• Subjects with a diagnosis of systemic lupus erythematosus according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria;
• This trial enrolled patients with refractory SLE and required the following prior treatment history for refractory patients:
• Adequate standard therapeutic doses of glucocorticoids, immunosuppressants, and at least one biologic therapy combination regimen for at least 2 months prior to screening are required, and the dose is stable for \>2 weeks and the disease remains moderately to severely active.
• Immunosuppressants: at least one or more of cyclophosphamide, mycophenolic acids, azathioprine, and calcineurin phosphatase inhibitors have been used;
• Biologics: at least one or more of belimumab, tetracycline, rituximab;
• Oral glucocorticoids must meet the following requirements:
• Prednisone (or equivalent) ≥ 7.5 mg/day and ≤ 60 mg/day;
• There is no minimum daily dose requirement for glucocorticoids when used in combination with immunosuppressive and/or biological agents.
• Compliance at screening: positive anti-nuclear antibodies (ANAs) or positive anti-dsDNA antibodies or positive anti-Smith antibodies;
• SLEDAI-2000 score ≥7 at screening or combination of vital organs, such as severe immune thrombocytopenia (platelets \<30\*×10\^9/L or \<50\*×10\^9/L with bleeding tendency);
• Age 18-70 (including boundary values), male and female;
• Survival is expected to be more than 3 months;
• Women of childbearing potential who had a negative blood pregnancy test prior to the start of the trial and who agreed to use effective contraception for the duration of the trial up to the last follow-up visit; male subjects whose partners were of childbearing potential agreed to use effective contraception for the duration of the trial up to the last follow-up visit;
• Blood cell analysis within 3 days prior to single collection:
• Hemoglobin (Hb) ≥ 80 g/L;

You may not qualify if:

• Pre-existing or clinically significant CNS disorders not due to lupus at the time of screening, such as convulsive seizures, epilepsy, epileptic seizures, cerebrovascular disease (ischemia/hemorrhage), cerebral edema, reversible posterior leukoencephalopathy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndromes, encephalitis, CNS vasculitis, or psychiatric disorders; epilepsy due to lupus, stable without seizures for a period of 1 year prior to the screening period Stable seizure-free for 1 year may also be screened.
• Treatment with hemodialysis, or high-dose corticosteroids (prednisone ≥1.5 mg/kg/d or equivalent glucocorticoid therapy for ≥14 days) was required within 2 months prior to screening.
• Presence of still uncontrolled lupus crisis within 2 months prior to screening that is assessed by the investigator to be unsuitable for participation in this study;
• Massive plasmapheresis (e.g., pleural effusion, abdominal effusion) with symptoms of compression that cannot be controlled with treatment;
• Active autoimmune disease other than SLE (e.g., Crohn's disease, rheumatoid arthritis) requiring systemic immunosuppressive therapy within 2 years prior to the start of screening;
• Patients who have previously received or are awaiting hematopoietic stem cell/bone marrow transplantation or organ transplantation;
• Those who have received prior genetically modified cell therapy, such as TCR-T therapy, CAR-T therapy, etc;
• Use of any other clinical investigational drug for the treatment of SLE within 4 weeks prior to screening. However, treatment ineffectiveness or disease progression that has passed at least 3 half-lives prior to screening will allow enrollment;
• History of grade ≥2 bleeding within 30 days prior to screening or need for long-term continuous treatment with anticoagulants (e.g., warfarin, low molecular heparin, or factor Xa inhibitors);
• Plasma exchange, plasma separation, hemodialysis, intravenous immunoglobulin (IVIG) within 14 days prior to cell collection;
• Those who used drugs to stimulate bone marrow hematopoietic cell production within 5 days prior to cell collection;
• Live or live attenuated vaccine within 6 weeks prior to screening;
• Active hepatitis B or hepatitis C virus, defined as subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and whose peripheral blood HBV-DNA test is above the lower limit of detection (HBsAg-positive but with a peripheral blood HBV-DNA test below the lower limit of detection according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B, 2022 Edition, at least 4 weeks of antiviral therapy prior to the first administration of the investigational drug, and continued antiviral therapy for 6 to 6 months during the study, with monitoring of HBV DNA and ALT levels required may be every 1\~month. Antiviral therapy for at least 4 weeks prior to the first dose of study drug and continued for 6-12 months during the course of the study, with monitoring of HBV DNA, HBsAg, and ALT levels at 1-3 month intervals); Hepatitis C Virus (HCV) antibody-positive subjects with a peripheral blood HCV-RNA test higher than the lower limit of detection; HIV antibody-positive subjects; and syphilis antibody-positive subjects;
• Active EBV and cytomegalovirus, defined as subjects with IgM antibody-positive or IgM antibody-negative EBV serum but higher-than-normal EBV-DNA; and cytomegalovirus (CMV) serum IgM antibody-positive or IgM antibody-negative cytomegalovirus but higher-than-normal CMV-DNA;
• Presence of chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and clinically significant pulmonary function test abnormalities;

Sponsors & Collaborators

• Beijing Immunochina Medical Science & Technology Co., Ltd.: lead
• Peking Union Medical College Hospital: collaborator

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Fei Wu

CONTACT

8615801390058; wufei@imunopharm.com

Mengtao Li, PhD

CONTACT

861065296114; Mengtao.li@cstar.org.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 18, 2025
• First Posted: February 28, 2025
• Study Start: February 20, 2025
• Primary Completion: February 20, 2026
• Study Completion (Estimated): August 20, 2027
• Last Updated: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share