Allogeneic Anti-CD7 CAR-T for Type 1 Diabetes
ConditionT1DM - Type 1 Diabetes Mellitus
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-40
SponsorShanghai Zhongshan Hospital
About this trial
Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease characterized by autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency and lifelong dependence on exogenous insulin. The disease results from loss of immune tolerance, with autoreactive T-cell responses against beta-cell antigens, and is typically associated with islet autoantibodies and insulitis. Although insulin therapy remains the standard of care, it does not correct the underlying autoimmune process.
Non-insulin therapeutic strategies for T1DM are mainly directed toward immunomodulation and beta-cell replacement or regeneration. Among immunomodulatory approaches, previous studies have primarily focused on regulation of effector T cells and B cells. Novel immune-based therapies are needed to explore whether modulation of pathogenic immune cell populations may alter disease activity and preserve residual beta-cell function.
The purpose of this study is to evaluate the safety, preliminary efficacy, and cellular kinetics of an allogeneic CD7-targeted CAR-T cell injection in participants with early stage T1DM. Participants will receive the investigational product and undergo regular assessments of safety, tolerability, treatment-emergent adverse events, cellular kinetics, glycemic parameters, exogenous insulin requirement, beta-cell function, and immunologic biomarkers. This study is expected to generate preliminary clinical evidence regarding the feasibility and potential therapeutic effects of CD7-targeted CAR-T cell therapy in T1DM.
Eligibility criteria
Qualifiers
Age ≥18 years and ≤40 years.
Participants with stage 2 or stage 3 type 1 diabetes mellitus, according to the staging criteria for type 1 diabetes defined in the ADA 2024 Standards of Care in Diabetes.
Positive for at least one islet autoantibody at screening, including glutamic acid decarboxylase autoantibody (GADA), insulinoma-associated protein 2 autoantibody (IA-2A), insulin autoantibody (IAA) (applicable only to participants who have received insulin therapy for no more than 2 weeks), zinc transporter 8 autoantibody (ZnT8A), or islet cell autoantibody (ICA). Participants positive for two or more autoantibodies will be prioritized for enrollment.
Peak C-peptide >0.2 nmol/L during a mixed-meal tolerance test (MMTT), or fasting C-peptide >0.1 nmol/L.
Disqualifiers
Any type of diabetes other than type 1 diabetes, such as gestational diabetes, monogenic diabetes, diabetes caused by pancreatic injury, or other secondary forms of diabetes (for example, diabetes caused by Cushing syndrome, thyroid dysfunction, or acromegaly).
Hematologic abnormalities at screening, including hemoglobin <100 g/L, white blood cell count <3 × 10^9/L, neutrophil count <1.5 × 10^9/L, or platelet count <75 × 10^9/L.
Liver injury at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 × the upper limit of normal (ULN), or total bilirubin ≥1.5 × ULN.
Severe heart disease, such as angina pectoris, myocardial infarction, heart failure, or clinically significant arrhythmia.
Trial design
Treatments tested in this trial
- Allogeneic CD7-Targeted CAR-T Cell Injection
Treatment groups
9 Participants
are divided into 1 treatment groupSponsors and collaborators
Source ClinicalTrials.gov