A Phase I/II Study of Eque-cel in Subjects Withimmune-mediated Necrotizing Myopathy

Official title

An Open-label, Single-arm Phase I/II Clinical Study to Evaluate the Safety and Efficacy of Equecabtagene Autoleucel Injection (Eque-cel) in Subjects With Immune-mediated Necrotizing Myopathy

Overview

This is an open-label, single-arm Phase I/II clinical study to evaluate the efficacy and safety of Eque-cel Injection in patients with refractory immune-mediated necrotizing myopathy.

Detailed description

This study is an open-label, single-arm Phase I/II clinical trial evaluating the safety and efficacy of Eque-cel in subjects with immune-mediated necrotizing myopathy (IMNM). The study consists of two phases: Phase I and Phase II. The Phase I component will evaluate the safety, tolerability and preliminary efficacy of Eque-cel to identify the recommended Phase 2 dose (RP2D). Following RP2D determination from Phase I, the Phase II stage will enroll additional subjects at this dose level to confirm the efficacy of Eque-cel injection in patients with IMNM. All subjects will undergo a primary follow-up period of 2 years after infusion of Eque-cel injection, followed by long-term follow-up extending up to 15 years.

Interventions

• Drug Equecabtagene Autoleucel Injection (Eque-cel)
  Eque-cel is a personalized, BCMA-targeted gene-modified autologous T-cell immunotherapy product capable of recognizing and eliminating both malignant and normal cells expressing BCMA. The CAR specifically identifies BCMA via a fully human single-chain variable fragment (scFv) with low immunogenicity, activates, proliferates, secretes cytokines, and kills target cells through the CD3ζ domain, while enhancing CAR-T expansion and persistence via 4-1BB costimulation signaling. Eque-cel demonstrates

Primary outcome measures

• Phase I: Safety endpoint - Adverse Events (AEs) [Time frame: up to 2 years from Eque-cel Injection infusion]
• Phase I: Safety endpoint-incidence of Dose-limiting toxicity (DLT) [Time frame: Time Frame: up to 28 days from Eque-cel Injection infusion]
• Phase II: Efficacy endpoint- TIS response [Time frame: up to the 2 years after Eque-cel Injection infusion]

Secondary outcome measures (12)

• Phase I: Efficacy endpoint -TIS response [Time frame: up to the 2 years after Eque-cel Injection Infusion]
• Phase II:Efficacy endpoint -Proportion of participants achieving minimal improvement response (TIS ≥ 20 points) [Time frame: From baseline to 12 months after Eque-cel Injection Infusion]
• Phase I/II:Efficacy endpoint -Change in mean Total Improvement Score (TIS) value [Time frame: up to 2 years from Eque-cel Injection infusion]
• Phase I/II:Efficacy endpoint -The changes in PtGA scores [Time frame: up to 2 years from Eque-cel Injection infusion]
• Phase I/II:Efficacy endpoint -The changes in PhGA scores [Time frame: up to 2 years from Eque-cel Injection infusion]
• Phase I/II:Efficacy endpoint-MMT-8 [Time frame: up to 2 years from Eque-cel Injection infusion]
• Phase I/II:Efficacy endpoint -HAO Scale [Time frame: up to 2 years from Eque-cel Injection infusion]
• Phase I/II:Efficacy endpoint -CK [Time frame: up to 2 years from Eque-cel Injection infusion]
• The changes in MDAAT scores [Time frame: up to 2 years from Eque-cel Injection infusion]
• Phase I/II:Efficacy endpoint -hormone dosage reduction [Time frame: From baseline to 6 and 12 months after Eque-cel Injection Infusion]
• Phase II:Safety endpoint - Adverse Events (AEs) [Time frame: up to 2 years from Eque-cel Injection infusion]
• Phase I/II Pharmacokinetic Endpoint - Cmax (CAR-T cells) [Time frame: up to 2 years from Eque-cel Injection infusion]

Eligibility criteria

Inclusion criteria

• 1\. At the time of signing the informed consent form, the age is ≥ 18 years old.
• 2.Based on the 2016 ENMC classification criteria, the clinical diagnosis is IMNM.
• 3.At the time of screening, the anti-SRP antibody or anti-HMGCR antibody is positive.
• 4\. Refractory IMNM that failed or relapsed after standard treatment, and the disease is still active at the time of screening.
• 5.The subjects must have appropriate organ functions.
• 6.The subjects and their spouses agree to take effective contraceptive measures (excluding safe period contraception) from the time of the subject signing the informed consent form until one year after the CAR-T cell infusion.
• 7\. The subjects must agree to sign or personally write and present the informed consent form approved by the ethics committee before starting any screening procedures.

Exclusion criteria

• 1\. Having end-stage myositis with involvement of terminal organs may pose additional risks or interfere with the study assessment.
• 2.Presence of irreversible muscle involvement and/or severe atrophy may bring additional risks or interfere with the study assessment.
• 3.Uncontrolled interstitial lung disease or any other uncontrolled manifestations of IIM, as judged by the investigator, may require the use of prohibited drugs during the study period.
• 4\. Diagnosed with other inflammatory or non-inflammatory myopathies.
• 5.Any other known autoimmune disease that the investigator considers to interfere with the accurate assessment of clinical symptoms of IMNM or place the patient at excessive risk.
• 6\. Those with a history of solid organ transplantation.
• 7\. History of autologous or allogeneic stem cell transplantation.
• 8\. Previous history of BCMA-targeted drug treatment.
• 9.Having occurred or planned to undergo major surgery or surgical treatment within 4 weeks before enrollment or within 12 weeks after infusion.
• 10\. Known primary immunodeficiency (congenital or acquired).
• 11\. Having a clear history of mental disorder or a history of substance abuse for mental disorders that cannot be quit.
• 12.The subject has uncontrollable active fungal， viral， bacterial or other infections (having persistent infection-related signs/symptoms， without improvement after appropriate anti-infection treatment) or infections requiring intravenous anti-infection drug treatment.
• 13.Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and abnormal peripheral blood hepatitis B virus (HBV) DNA test (defined as HBV DNA quantification ≥ 100IU/ml or ≥ 1000 copies /ml or above the normal reference range of the testing center or positive for qualitative HBV DNA detection) ; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive (defined as ≥ 1000 IU/mL); human immunodeficiency virus (HIV) antibody positive; cytomegalovirus (CMV) DNA positive (defined as ≥ 1000 IU/mL); Treponema pallidum specific antibody positive and positive for the rapid plasma reagin test for syphilis.
• 14.Severe heart disease: including but not limited to unstable angina pectoris and/or myocardial infarction within 12 months of the screening period, any congestive heart failure (NYHA classification ≥ III), and a history of severe arrhythmia.
• 15.Severe asthma or chronic obstructive pulmonary disease (COPD). Note: Mild or moderate asthma or COPD patients with stable conditions, after assessment and approval by the investigator and the sponsor, can be enrolled.
• 16.Acute cerebrovascular disease events occurred within 6 months before enrollment, including transient ischemic attack or stroke history.
• 17.Any serious and/or uncontrolled comorbid diseases as determined by the investigator to potentially interfere with the study assessment.
• 18.Malignant tumors within 5 years before screening, excluding cured cervical carcinoma in situ, basal cell or squamous epithelial cell skin cancer, locally advanced prostate cancer after radical surgery, breast duct carcinoma in situ after radical surgery, or thyroid papillary carcinoma after radical surgery.
• 19\. Known history of allergy to cyclophosphamide, fludarabine, components of Eque-cel injection or supportive drugs required for toxicity management of CAR-T cell therapy (such as tocilizumab).
• 21.Pregnant or lactating women.
• 21\. Other situations as determined by the investigator to be unsuitable for enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• China-Japan Friendship Hospital — Beijing
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou
• Huashan Hospital of Fudan University — Shanghai
• The Second Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07752264 · CT103AC006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗