Clinical Study of EVM18001 in the Treatment of Refractory Autoimmune Diseases

NCT07470151 | Recruiting

• 1 other identifier: EVM18CX01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

A FIH, single arm, open-label, Investigator Initiated Trial (IIT) study to evaluate the safety and tolerability of EVM18001 in the treatment of active refractory autoimmune diseases (SLE, MG, and SSc), and determine the recommended dose for subsequent treatment. At the same time, the PK/PD characteristics of EVM18001 will be evaluated, preliminary efficacy will be observed, and related biomarkers and immunogenicity will be explored.

Conditions

System Lupus Erythematosus(SLE); Scleroderma; Myasthenia Gravis (MG)

Keywords

Active Refractory Systemic Lupus Erythematosus; Myasthenia Gravis; Scleroderma; EVM18001; CAR-T; Refractory Autoimmune Diseases

Outcome Measures

Primary Outcomes (7)

• Evaluate the safety/tolerability of EVM18001 in patients with SLE/MG/SSc by rates and severity of AE/SAE.

  Subsequent recommended dose will be determined by the results of the clinical study.

  Day 1 ~ Month 24

• Determine the subsequent recommended dose of EVM18001 in patients with SLE/MG/SSc.

  Subsequent recommended dose will be determined by the results of the clinical study.

  Day 1~ Month 24

• Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by proportion of patients get relief during the whole study.

  Evaluated by PI

  Day 1 ~ Month 24

• Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by Duration of Response (DOR).

  Evaluated by PI

  Day 1 ~ Month 24

• Cmax of EVM18001 and CAR-T cells.

  Samples will be sent to the central laboratory for testing and analysis. The content of peripheral blood mRNA EVM18001 will be detected by quantitative polymerase chain reaction (qPCR), the concentration of ionizable lipid L84 will be measured by liquid chromatography-mass spectrometry (LCMS), and the pharmacokinetic characteristics after EVM18001 administration will be monitored by detecting peripheral blood CAR-T cells using flow cytometry.

  Day1~ Day29

• AUC0-t of EVM18001 and CAR-T cells.

  Samples will be sent to the central laboratory for testing and analysis. The content of peripheral blood mRNA EVM18001 will be detected by quantitative polymerase chain reaction (qPCR), the concentration of ionizable lipid L84 will be measured by liquid chromatography-mass spectrometry (LCMS), and the pharmacokinetic characteristics after EVM18001 administration will be monitored by detecting peripheral blood CAR-T cells using flow cytometry.

  Day1~ Day29

• Detection of CAR expression on the surface of immune cells in peripheral blood.

  PD indicator

  Day1~ Day29

Secondary Outcomes (7)

• Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by proportion of patients relieve after 6 months.

  Day 1 ~ Month 24

• Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by proportion of patients get relapse during the whole study.

  Day 1 ~ Month 24

• Evaluate the efficacy of EVM18001 in patients with SLE/MG/SSc by proportion of patients achieving no hormone/immunosuppressant use or low-dose hormone use during the whole study.

  Day 1 ~ Month 24

• PK detection of EVM18001 in peripheral blood.

  Day1~ Day29

• Tmax of EVM18001 and CAR-T cells.

  Day1~ Day29

Study Arms (1)

EVM18001 Injection

EXPERIMENTAL

All enrolled participants will receive multiple doses of EVM18001 according to the assigned dosage group.

Biological: EVM18001 Injection

Interventions

EVM18001 Injection BIOLOGICAL

All enrolled participants will receive multiple doses of EVM18001 according to the assigned dosage group.

EVM18001 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:

• Voluntarily sign the Informed Consent Form (ICF), which must be signed by the participant or their legal guardian.
• At the time of signing the ICF, the age must be between 18 and 70 years (inclusive), regardless of gender.
• At screening, peripheral blood B cells must be CD19 positive, and T cells must express CD7.
• Confirmed autoimmune diseases based on recognized diagnostic criteria, including:
• SLE: Diagnosed with SLE according to the 2012 Systemic Lupus International Collaborating Clinics (SLICC) or 2019 European League Against Rheumatism (EULAR)/ACR criteria;
• MG: Diagnosed with MG according to the Myasthenia Gravis Foundation of America (MGFA) clinical classification;
• SSc: Diagnosed with SSc according to the 2013 ACR/EULAR classification criteria.
• History of autoimmune disease for at least 6 months before screening and meets any of the following criteria. Definitions of active refractory SLE, active refractory SSc, and active refractory MG are as follows:
• Definition of active refractory SLE: SLEDAI-2000 score ≥6; and disease activity or relapse persists after at least 3 months of standard therapy (glucocorticoids combined with at least 2 immunosuppressants, or at least 1 imunosuppressant and 1 targeted therapy).
• Definition of active refractory SSc: Patients meeting the 2013 ACR/EULAR classification criteria for SSc who still show disease activity or progression after at least 6 months of standard therapy (including steroids, immunosuppressants, vasodilators, or antifibrotic agents). Specific criteria include but are not limited to: mRSS increase ≥5 points or ≥25% from baseline; absolute value of predicted FVC% decrease ≥5%; DLCO% corrected for hemoglobin absolute value decrease ≥10%; new or worsening digital ulcers after ≥3 months of vasodilator therapy; persistent or recurrent organ involvement requiring intensified treatment.
• Definition of active refractory MG: Refers to generalized MG patients meeting MGFA diagnostic criteria with ongoing disease activity (MGFA II-IV, QMG ≥12, or MG-ADL ≥6), and includes at least one of the following: poor control after at least 12 months of standard therapy (including at least 2 immunosuppressants); need for ≥2 intravenous immunoglobulin (IVIG) or plasma exchange treatments in the past 12 months to control symptoms; relapse with prednisone ≥20 mg/day or reduction to \<10 mg/day; persistent or recurrent disease activity.
• Patients must meet the following conditions for concomitant medication:
• Corticosteroids must have been used for more than 6 weeks prior to screening and at a stable dose of ≤ 10 mg/day prednisone or equivalent for at least 14 days prior to administration of EVM18001. Concurrent treatment with topical or inhaled corticosteroids (or other immunomodulators) is allowed;
• Continued use during treatment is allowed if antimalarial drugs (eg, hydroxychloroquine, chloroquine, etc.) are started ≥ 12 weeks prior to screening and maintained at a stable dose for ≥ 8 weeks (maximum dose limit: hydroxychloroquine, 400 mg/day; chloroquine, 500 mg/day).
• Examination at screening meet any of the following criteria:

You may not qualify if:

• Concurrent autoimmune diseases requiring systemic treatment.
• The autoimmune disease meets the following criteria:
• SLE: patients with renal crisis;
• MG: MGFA clinical classification type V or experiencing myasthenic crisis;
• SSc: involving lungs and exist severe ILD and severe PAH, or patients with scleroderma renal crisis.
• Any of the following conditions exist:
• Positive for Hepatitis B surface antigen (HBsAg)/core antibody (HBcAb)/e-antibody (HBeAb)/e antigen (HBeAg);
• Positive for Hepatitis C virus (HCV) antibody;
• Positive for human immunodeficiency virus (HIV) antibody;
• Positive CMV DNA or above the upper limit of detection;
• Positive for syphilis antigen or antibody.
• Other uncontrolled active infections exist at screening.
• Creatinine clearance \<50 mL/min.
• Estimated glomerular filtration rate \<45 mL/min/1.73m² (calculated using the MDRD creatinine equation from the Chronic Kidney Disease Epidemiology Collaboration; or serum creatinine \>2.0 mg/dL.
• History of major organ transplantation (such as heart, lung, liver, kidney) or bone marrow/hematopoietic stem cell transplantation.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Everest Medicines (China) Co.,Ltd.: collaborator

Study Sites (1)

Union hospital Tongji medical college Huazhong university of science and technology

Wuhan, Hubei, 430022, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Scleroderma, Diffuse; Myasthenia Gravis; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Scleroderma, Systemic; Skin Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases

Study Officials

• Qiubai Li, Professor

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qiubai Li, professor

CONTACT

85726808; qiubaili@hust.edu.cn

Di Wu

CONTACT

18790696175; 373181302@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of Department of Rheumatology and Immunology, Principal Investigator, Professor, Wuhan Union Hospital

Model Details: DL1 and DL2 use an accelerated titration design, enrolling 1-3 trial participants. If the first participant in each dose group does not experience dose-limiting toxicity (DLT), the dose is rapidly escalated to the next group; if DLT occurs, the Safety Review Committee (SRC) will discuss whether to reduce the dose (DL1 will be reduced to DL-1) or to expand enrollment by 3 participants. DL3 uses a "3#+#3" dose escalation, enrolling 3 participants; if no DLT occurs, the dose is rapidly escalated to the next group; if DLT occurs, enrollment is expanded by 3 participants. DL4 also uses a "3#+#3" dose escalation, first enrolling 3 participants; if none of the first 3 experience DLT, further dose escalation may be considered; if 1 of the first 3 participants experiences DLT, 3 additional participants are enrolled; if ≥2 of the first 3 participants, or ≥2 of a total of 6 participants, experience DLT, dose escalation is stopped.

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 13, 2026
• Study Start: March 12, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)