Type 1 diabetes mellitus MedDRA version: 21.1 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Thymoglobulin / Thymoglobuline
Product Name: Thymoglobuline 25 mg powder for solution for infusion
Pharmaceutical Form: Powder for solution for infusion
Pharmaceutical form of the placebo:
Sponsors
Universitair Ziekenhuis Leuven (UZ Leuven)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has given written informed consent to participate; or have a parent or legal guardian provide written informed consent. Individuals under the age of consent will be asked to assent to trial participation. 2. Be aged =5 years to =25 years at written informed consent/assent 3. Have been diagnosed with T1D within 3–9 weeks of planned treatment day 1 4. Have random C-peptide levels =200 pmol/L measured at screening, as tested centrally 5. Have 1 or more diabetes-related autoantibody (GADA, IA-2A or ZnT8A) present at screening, as tested centrally 6. Will be =6 weeks from last live immunisation at planned treatment day 1 and be willing to forgo live vaccines during the trial until 6 months post treatment 7. Be willing to comply with intensive diabetes management Are the trial subjects under 18? yes Number of subjects for this age range: 107 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Type 2 diabetes 2. Evidence of prior or current tuberculosis (TB) infection 3. Clinically significant abnormal full blood count (FBC), renal function or liver function at screening, including: - Immunodeficient or clinically significant chronic leucopenia, neutropenia, lymphopenia or thrombocytopenia at the screening visit, according to local reference ranges - Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limit of normal (ULN), at screening - Evidence of renal dysfunction with creatinine greater than 1.5 times the ULN at screening, adjusted for the age of the patient - Clinically significant clotting disorder, according to local reference ranges 4. Requiring use of other immunosuppressive or immunomodulation agents, including chronic use of systemic steroids 5. Any active chronic infections at screening, or any active acute or chronic infections at baseline or on treatment day, which would contraindicate any additional immunosuppression 6. Seropositive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection at screening 7. Positive for SARS-CoV-2 based on local testing regimen 8. Unwilling to use appropriate contraception if sexually active during the trial, from date of written informed consent until completion of the 12-month follow up visit 9. Any history of malignancies 10. Current or ongoing use of non-insulin pharmaceuticals that affect glycaemic control 11. Active participation in another T1D treatment interventional trial in the previous 30 days prior to screening (excluding treatment with insulin) 12. Any prior treatment with ATG, Abatacept or anti-CD3 13. Known allergy to ATG or to similar products, or hypersensitivity to rabbit proteins or to any of the excipients 14. Any condition, complicating medical issues, or abnormal clinical laboratory results that the investigator judges may adversely affect trial conduct, cause increased risk to the participant, or compromise the trial results 15. Pregnant and breastfeeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine the changes in stimulated C-peptide response over the first two hours of a mixed meal tolerance test (MMTT) at 12 months for 2.5mg/kg ATG arm versus the placebo. • Conditional on finding a statistical difference between the 2.5mg/kg ATG arm and placebo, to identify the minimally effective dose (lowest dose significantly different to placebo) amongst the doses studied in the trial using change in stimulated C-peptide response over the first two hours of a MMTT at 12 months versus placebo. ;Secondary Objective: • To determine the effects of ATG treatment on: - MMTT-stimulated C-peptide (at baseline, 3, 6 and 12 months) - HbA1c and total daily insuline dose (units/kg) (at baseline, 3, 6, 12 months) - Fasting/stimulated dried blood spot (DBS) C-peptide measurements (monthly) - CGM measures over 14 days at 3, 6 and 12 months • To determine whether ATG treatment mediates a reduction in CD4 positive T-cells but relative preservation of CD8 positive T-cells • Descriptive analysis of the safety profile of different doses of ATG in different age groups ;Primary end point(s): The area under the stimulated C-peptide response curve.;Timepoint(s) of evaluation of this end point: Measured over the first 2 hours of a MMTT at 12 months after treatment follow up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The area under the stimulated C-peptide response curve over the first 2 hours of a mixed meal tolerance test (MMTT) 2. Dried blood spot (DBS) C-peptide measurements 3. CD4-positive T cells and CD8-positive T cells 4. HbA1c 5. Insulin requirements 6. T1D-associated autoantibodies (GADA, IAA, IA-2A and ZnT8A) 7. CGM measures (time in range, time above, time below);Timepoint(s) of evaluation of this end point: 1. At baseline, 3, 6 and 12 months 2. At all observation times 3/4/5/6/7. Over 12 months | — |
Countries
Austria, Belgium, Denmark, Finland, Germany, Italy, Slovenia, United Kingdom
Contacts
Public ContactMELD-ATG Trial Coordinator
Univeristy of Cambridge
Outcome results
None listed