Sequential Immune Modulation and Antigen-Specific Tolerance Induction for Disease Modification in Recent-Onset Type 1 Diabetes

NCT07610213 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: KHO-MATIN2-2026CRD420261394024
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study tests a three-phase immune treatment for people recently diagnosed with Type 1 diabetes (within 6 months, with some insulin production remaining). Phase 1 (weeks 1-2): Teplizumab, an anti-CD3 antibody, is given by infusion to slow immune attack on insulin-producing beta cells. Phase 2 (months 2-9): Insulin is injected directly into a lymph node (intralymphatic immunotherapy, ILIT) alongside low-dose interleukin-2 to teach the immune system to tolerate insulin and expand protective regulatory T cells. Phase 3 (months 10-24): Low-dose interleukin-2 is continued to maintain immune tolerance. The main goal is to preserve the body's remaining insulin production (measured by C-peptide). Sixty adults aged 18-45 will be randomly assigned to the MATIN-2 protocol or standard care. Safety, immune markers, and HbA1c will also be monitored.

Conditions

Type 1 Diabetes Mellitus (T1DM); Type 1 Diabetes Mellitus; Autoimmune Diabetes

Keywords

teplizumab; intralymphatic immunotherapy; regulatory T cells; immune tolerance; C-peptide; beta cell preservation

Outcome Measures

Primary Outcomes (1)

• Change in Stimulated C-peptide AUC

  Area under the curve of C-peptide response during mixed-meal tolerance test (MMTT); reflects residual beta-cell function

  Baseline, 6, 12, and 24 months

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Throughout 24 months

Study Arms (2)

MATIN-2 Protocol

EXPERIMENTAL

Three-phase sequential immunotherapy: teplizumab (Weeks 1-2), intralymphatic insulin immunotherapy + low-dose IL-2 (Months 2-9), maintenance low-dose IL-2 (Months 10-24)

Drug: Teplizumab; Biological: Intralymphatic Insulin Immunotherapy (ILIT)

Standard Care

NO INTERVENTION

Conventional insulin therapy per standard clinical guidelines

Interventions

Teplizumab DRUG

Anti-CD3 monoclonal antibody; 14-day IV infusion course at standard dosing (Days 1-14)

MATIN-2 Protocol

Intralymphatic Insulin Immunotherapy (ILIT) BIOLOGICAL

Insulin antigen injected directly into inguinal lymph node; 3 injections at monthly intervals (Months 2-4) combined with low-dose IL-2

MATIN-2 Protocol

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 years
• Clinical diagnosis of Type 1 diabetes mellitus within 6 months of enrolment
• Positive for at least one diabetes-related autoantibody (GAD65, IA-2, ZnT8, or IAA)
• Detectable fasting or stimulated C-peptide ≥ 0.2 nmol/L
• HbA1c ≤ 10% (86 mmol/mol)
• Ability to provide written informed consent

You may not qualify if:

• Prior immunosuppressive therapy within 3 months
• Active or chronic infection (HIV, hepatitis B/C, tuberculosis)
• Current or prior malignancy within 5 years (except non-melanoma skin cancer)
• Pregnancy or breastfeeding
• Severe renal impairment (eGFR \< 30 mL/min/1.73m²)
• Severe hepatic impairment (Child-Pugh C)
• Known hypersensitivity to teplizumab or any excipient
• Participation in another interventional trial within 30 days
• Current systemic corticosteroid or immunomodulatory agent use
• History of other autoimmune disease requiring immunosuppression
• Absolute lymphocyte count \< 1.0 × 10⁹/L
• ALT or AST \> 3× upper limit of normal
• Haemoglobin \< 100 g/L
• Unwillingness to use contraception during study period

Sponsors & Collaborators

• Abdullah Kars: lead

Study Sites (1)

Kara Harp Okulu (Turkish Military Academy)

Ankara, Ankara, 06000, Turkey (Türkiye)

Location

Related Links

• Research Square preprint: MATIN-2 protocol paper

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

teplizumab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Abdullah Kars

CONTACT

+905057977996; fly.pgs@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcomes assessors performing laboratory analyses (C-peptide, HbA1c, immune markers) will be blinded to treatment allocation. Participants and care providers will not be blinded due to the nature of the interventions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Lieutenant Colonel, Kara Harp Okulu (Turkish Military Academy)

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: May 27, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IPD will be available beginning 6 months after primary results publication, for a period of 5 years.
• Access Criteria: Researchers with a methodologically sound proposal may request access. Requests should be directed to the principal investigator (fly.pgs@hotmail.com). Data will be shared as de-identified datasets following execution of a data sharing agreement.

Locations

TU (1)