Autoimmune Diabetes, Type 1 Diabetes Mellitus, Type 1 Diabetes Mellitus (T1DM)
Conditions
Keywords
teplizumab, intralymphatic immunotherapy, regulatory T cells, immune tolerance, C-peptide, beta cell preservation
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.
Interventions
DRUGTeplizumab
Anti-CD3 monoclonal antibody; 14-day IV infusion course at standard dosing (Days 1-14)
BIOLOGICALIntralymphatic Insulin Immunotherapy (ILIT)
Insulin antigen injected directly into inguinal lymph node; 3 injections at monthly intervals (Months 2-4) combined with low-dose IL-2
Sponsors
Abdullah Kars
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Stimulated C-peptide AUC | Baseline, 6, 12, and 24 months | Area under the curve of C-peptide response during mixed-meal tolerance test (MMTT); reflects residual beta-cell function |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | Throughout 24 months | Safety assessment including serious adverse events, hypoglycaemia, and immune-related adverse events |
Countries
Turkey (Türkiye)
Contacts
CONTACTAbdullah Kars
Outcome results
None listed