Autologous CD6-CAR Treg Cells for Patients With Stage 3 Type 1 Diabetes

NCT07395050 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 24895
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Type 1 diabetes (T1D) is a persistent and gradually increasing genetic autoimmune disease requiring life-long management. The disease commonly impacts children. However, a quarter of cases are diagnosed in adults. The pancreatic islet beta-cells are responsible for producing insulin, a peptide hormone that is involved in the tight regulation of blood glucose levels. In T1D, the beta-cells are mistakenly destroyed by autoreactive T cells resulting in insulin deficiency and an inability to regulate blood glucose levels. The cause for such an autoimmune reaction to beta-cells is under active investigation. T regulatory cells (Tregs), are specialized immune cells that typically act to control your immune system. Tregs can be modified in the laboratory to recognize and deactivate T1D-causing cells. This process is done by inserting a piece of DNA (the molecules inside cells that carry genetic information and pass it from one generation to the next) into the Tregs. A non-infectious virus called a lentivirus will carry the piece of DNA into the cells that were collected from a donor. Tregs are then grown to large numbers in the laboratory and stored for treatment of T1D. It is not known whether these Tregs cells will treat T1D.

Conditions

Stage 3 Type 1 Diabetes

Keywords

Type 1 Diabetes; CAR T cell Therapy; CAR-Treg cells

Outcome Measures

Primary Outcomes (2)

• Toxicity, CRS, ICANS, hyperglycemia/DKA

  Toxicity will be graded according to the CTCAE version 65.0; cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) will be assessed per ASTCT consensus criteria \[8\]; Hyperglycemia/DKA will be graded per the Clinical Islet Transplant Consortium Terminology Criteria for Adverse Events (CIT-TCAE). Unacceptable toxicity (UT) and moderate toxicity (MOD) are defined in Section 11.2. All patients who are not evaluable for UT or MOD will be replaced.

  till 28 days post investigational drug infusion

• Feasibility of investigational product manufacture

  Feasibility will be assessed by achieving both following conditions. * ability to meet at least 80% of the required cell dose at the assigned dose level and * ability to meet the required product release criteria.

  till 28 days post investigational drug infusion

Secondary Outcomes (4)

• Change in insulin levels

  at baseline (pre-intervention), 3, 6 and 12 months post last CAR T cell infusion through study completion, an average of 1 year'

• Change in stimulated C-peptide levels

  at baseline (pre-intervention), 3, 6 and 12 months post last CAR T cell infusion through study completion, an average of 1 year'

• Change in continuous glucose monitoring (CGM) metrics levels

  at baseline (pre-intervention), 3, 6 and 12 months post last CAR T cell infusion through study completion, an average of 1 year'

• Change in Hb1Ac levels

  at baseline (pre-intervention), 3, 6 and 12 months post last CAR T cell infusion through study completion, an average of 1 year'

Study Arms (1)

I.V. infusion of autoCD6-CAR Treg cells

EXPERIMENTAL

I.V. infusion of autoCD6-CAR Treg cells

Drug: AutoCD6-CAR Treg cells

Interventions

AutoCD6-CAR Treg cells DRUG

The investigational product is an autologous (patient-derived) anti-CD6 chimeric antigen receptor (CD6-CAR) T regulatory cell (Treg) cellular product (CD6-CAR Tregs).

I.V. infusion of autoCD6-CAR Treg cells

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Informed Consent and Willingness to Participate
• \. Documented informed consent of the participant
• Note: For research participants who do not speak English, a short form consent may be used with a COH certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed. However, the research participant can proceed with lymphodepletion (if applicable) and CAR T cell infusion only after the translated full consent form is signed.
• \. Willingness to continue into follow-up assessments for up to 15 years after autoCD6-CAR Treg treatment
• \. Willingness to wear a study continuous glucose monitoring device (CGMD) for 2 weeks prior to mandated study visits for at least 1 year of follow-up post last CAR Treg infusion.
• i. For participants who have a personal CGMD: Willingness to wear a second CGMD during mandated study CGMD visits Age, Nature of Illness and Transplant Related Criteria
• \. Age: 18-35 years old
• \. Stage 3 T1D diagnosed by standard ADA Criteria, with residual beta cell function, enrolled between 12 and 24 months from the date of T1D diagnosis.
• Date of diagnosis is defined as the date that diabetes was confirmed by standard ADA criteria.
• Historical or current presence of at least one type-1 diabetes associated autoantibody other than insulin autoantibodies, such as:
• \- GAD specific autoantibodies (GADA); and/or
• \- Islet-antigen 2 specific autoantibody (IA-2A); and/or
• \- Zinc Transporter 8 specific autoantibody (ZNT8A)
• Must have stimulated C-peptide levels ≥ 0.2 nmol/L measured during a 2-hr mixed meal tolerance test (MMTT) conducted prior to enrollment.
• i. MMTTs will be coordinated with the Diabetes team and will be collected between 7-10am on the days of collection. Results may take 5-10 business days to be available.

You may not qualify if:

• Prior and concomitant medications/therapies
• \. Prior treatment with Itolizumab or other CD6-directed therapies.
• \. Prior or current participation in research study in which a potential participant received an immunomodulatory agent or diabetes care, unless the participant was in the placebo arm.
• \. Other investigational agents, biologics (including cellular immunotherapies)
• \. Anti-inflammatory therapy (Exception: Over-the-counter (OTC) anti-inflammatory agents (e.g. ibuprofen, Tylenol) are generally allowed)
• \. Systemic corticosteroids within 14 days prior to leukapheresis
• \. Systemic immunosuppressive therapy (e.g., cyclosporine-A, cyclophosphamide)
• \. Vaccine(s) within 8 weeks of leukapheresis
• \. Prior organ transplant
• \. Last dose of Beta-cell stimulants (e.g., sulphonylureas), glucagon-like peptide-1 agonists, dipeptidyl peptidase-IV inhibitors, insulin sensitizers (e.g., metformin, thiazolidinediones), verapamil, must be at least 30 days prior to enrollment.
• Other illnesses or conditions
• \. Unstable cardiac disease as defined by one of the following:
• \. Uncontrolled arrhythmia and/or coronary artery disease
• \. Cardiac events such as myocardial infarction (MI) within the past 6 months
• \. NYHA (New York Heart Association) heart failure class III-IV

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Matthew Mei, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arthur Riggs Diabetes & Metabolism Research Institute

CONTACT

866-444-7538; islets@coh.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: While this is not a maximum tolerated or recommended phase 2 dose (MTD/RP2D) finding (phase I) study, out of an abundance of caution, 1+1+1 dose expansion/de-escalation rules based on observed toxicity at a dose level are used. Among the first cohort of 3 patients at a dose level, we will enroll one patient at dose level 1 and evaluable unacceptable toxicity (UT) and moderate toxicity (MOD) during the observation period each time. If 0 of 3 evaluable participantsat dose level 1 has UT and at most 1 of them has MOD during the observation period, we will treat another cohort of 3 patients at dose level 2 using the same rule. Accrual suspension will be triggered as soon as a patient experiencing UT or MOD safety boundary is crossed. We will conduct safety review and submit a report to COH DSMC.

Study Record Dates

• First Submitted: January 27, 2026
• First Posted: February 9, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 14, 2026
• Study Completion (Estimated): September 14, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (1)