Allogeneic Anti-CD7 CAR-T for Type 1 Diabetes

Official title

A Study on the Safety, Preliminary Efficacy, and Cellular Kinetics of Allogeneic CD7-Targeted CAR-T Cell Injection for the Treatment of Type 1 Diabetes Mellitus

Overview

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.

Interventions

• Biological Allogeneic CD7-Targeted CAR-T Cell Injection
  RD13-02 will be administered as a single intravenous infusion using a dose-escalation design. The starting dose is dose level 1 (DL1, 5×10\^7). If no dose-limiting toxicity (DLT) is observed within 28 days after infusion, dose escalation will proceed to dose level 2 (DL2, 1×10\^8). If a DLT is observed, the cohort will be expanded to 6 participants and subsequent dose decisions will follow the standard 3+3 design. The study will be terminated if 2 participants experience DLTs at DL1. If DL1 show

Primary outcome measures

• Safety: Incidence of dose-limiting toxicities (DLTs), adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) in participants with type 1 diabetes mellitus treated with RD13-02. [Time frame: From the date of signing informed consent to 3 months after CAR-T cell infusion.]
• Change from baseline in 4-hour MMTT C-peptide AUC at Months 3, 6, and 12. [Time frame: From baseline to Month 12.]

Secondary outcome measures (11)

• Change from baseline in peak C-peptide during a mixed-meal tolerance test (MMTT) at Months 3, 6, and 12. [Time frame: From baseline to Month 12.]
• Change from baseline in blood glucose area under the curve (AUC) during a mixed-meal tolerance test (MMTT) at Months 3, 6, and 12. [Time frame: From baseline to Month 12.]
• Change from baseline in mean daily dose of exogenous insulin at Months 1, 3, 6, 9, and 12. [Time frame: From baseline to Month 12.]
• Change from baseline in glycated hemoglobin (HbA1c) at Months 3, 6, 9, and 12. [Time frame: From baseline to Month 12.]
• Change from baseline in fasting blood glucose at Months 1, 3, 6, 9, and 12. [Time frame: From baseline to Month 12.]
• Change from baseline in time in range (TIR, %) on continuous glucose monitoring (CGM), defined as the percentage of time with glucose levels between 70-180 mg/dL (3.9-10.0 mmol/L), at Months 3, 6, and 12. [Time frame: From baseline to Month 12.]
• Proportion of participants with HbA1c ≤7.0% and a reduction of ≥50% in insulin dose at Month 12. [Time frame: Month 12.]
• Proportion of participants with MMTT C-peptide AUC >0.2 nmol/L at Month 12. [Time frame: Month 12.]
• Incidence of clinically significant hypoglycemic events during the study period. [Time frame: From baseline to Month 12.]
• Incidence of diabetic ketoacidosis (DKA) events. [Time frame: From baseline to Month 12.]
• Expansion and persistence of RD13-02 in participants with type 1 diabetes mellitus. [Time frame: From infusion through Month 12.]

Eligibility criteria

Inclusion criteria

• 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.
• The participant or his/her legally authorized representative voluntarily agrees to participate in the study and is able to sign the informed consent form.

Exclusion criteria

• 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.
• kidney disease, including severe diabetic kidney disease, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², current or expected receipt of renal replacement therapy.
• Ongoing use of medications that, in the investigator's judgment, may cause significant and sustained changes in the course of type 1 diabetes or immune status.
• Uncontrolled diabetic ketoacidosis.
• Uncontrolled infection at screening, or any of the following at screening: positive hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg); positive hepatitis B e antibody (HBeAb) with peripheral blood HBV DNA above the upper limit of normal; positive hepatitis C virus (HCV) antibody; positive human immunodeficiency virus (HIV) antibody; positive syphilis antibody; positive Epstein-Barr virus-encoded RNA (EBER), or EBV viral load above the upper limit of normal.
• Active autoimmune disease other than type 1 diabetes that requires systemic immunotherapy or is associated with organ dysfunction.
• Pregnant or breastfeeding women; participants planning to conceive within 1 year; or participants of childbearing potential who are unwilling to use effective contraception during the study.
• History of malignancy, except for cases considered by the investigator to be cured and at no risk of recurrence.
• Participation in another clinical study within 3 months before enrollment.
• Receipt of a live attenuated vaccine within 4 weeks before enrollment, or plan to receive a live attenuated vaccine during the study period.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for this study.

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 · 1 center

• Zhongshan Hospital, Fudan University — Shanghai

Identifiers

NCT: NCT07528105 · B2026-141R

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗