MELD-ATG

Dose ranging, efficacy study of anti-thymocyte globulin (ATG) in subjects within six weeks of diagnosis of type 1 diabetes (T1D)

Research summary

MELD-ATG is a multi-centre, randomised, double-blind, placebocontrolled, multi-arm parallel cohort trial. The purpose of this clinical trial is to confirm the effect of 2.5mg/kg of antithymocyte globulin (ATG) on the preservation of stimulated C-peptide at 12 months compared to placebo. It is also to identify the minimally effective dose of ATG that shows a statistically different effect on C-peptide when compared to placebo at 12 months.

The primary objective is to determine the changes in stimulated C-peptide response during the first two hours of a mixed meal tolerance test (MMTT) at baseline and 12 months for placebo versus the highest dose arm (2.5mg/kg). Conditional on finding a statistical difference of 2.5mg/kg ATG dose versus placebo then a minimally effective dose will be identified from all the dose arms

Main inclusion criteria

  1. Have given written informed consent to participate or have a parent or legal guardian provide informed consent if the subject is under the age of consent (age may vary in different countries; <16 years of age in UK)

  2. Age ≥7 years <25 years at consent

  3. Must have a diagnosis of T1D of within 6 weeks duration at screening

  4. Must have at least two diabetes-related autoantibody present at screening

  5. Must have random C-peptide levels ≥200 pmol/L measured at screening

  6. Must be Epstein-Barr virus (EBV PCR) negative within two weeks of randomization if EBV seronegative at screening

  7. Be at least 6 weeks from last live immunization at randomisation

  8. Participants are required to receive killed influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available

  9. Be willing to forgo live vaccines for 3 months following last dose of study drug

  10. Be willing to use appropriate contraception if sexually active

  11. Be willing to comply with intensive diabetes management

  12. Normal screening values for complete blood count (CBC), renal function and electrolytes (CMP).

Main exclusion criteria

  1. Be immunodeficient or have clinically significant chronic lymphopenia: (Leukopenia (< 3,000 leukocytes /µL), neutropenia (<1,500 neutrophils/µL), lymphopenia (<800 lymphocytes/µL), or thrombocytopenia (<100,000 platelets/µL).

  2. Have active signs or symptoms of acute infection at the time of treatment

  3. Have evidence of prior or current tuberculosis infection as assessed by purified protein derivative (PPD), interferon gamma release assay (IGRA) or by history

  4. Be currently pregnant or lactating, or anticipate getting pregnant within the two year study period

  5. Require use of other immunosuppressive agents including chronic use of systemic steroids

  6. Have evidence of current or past human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection

  7. Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, chronic obstructive pulmonary disease (COPD), sickle cell disease, neurological, or blood count abnormalities

  8. Have a history of malignancies other than skin

  9. Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal

  10. Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal

  11. Vaccination with a live virus within the last 6 weeks

  12. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening

  13. Active participation in another T1D treatment study in the previous 30 days

  14. Prior treatment with abatacept or anti-cd3

  15. Known allergy to ATG

  16. Prior treatment with ATG or known allergy to rabbit derived products

  17. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

Funders and sponsors

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