Diabetes Prevention - Immune Tolerance
Condition: Prediabetes; Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Placebo comparator; Diamyd
Intervention description: Placebo comparator day 1 and 30 in non-diabetic children with multiple islet autoantibodies.
Post diagnosis: Two doses of 20 microgram Diamyd day 1 and 30 in children originally receiving placebo.; 20 microgram day 1 and 30 in non-diabetic children with multiple islet autoantibodies.
Post diagnosis: Two doses of Diamyd followed to children originally receiving Diamyd
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 50.0
Sex: All
Minimum age: 4 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Alum-GAD; Type 1 diabetes; prevention; immune tolerance; glucose tolerance; glutamate decarboxylase autoantibodies

Summary:

      A double-blind, randomized investigator-initiated study to determine the safety and the
      effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell
      autoantibodies

      Eligible children are 4 years or older, have positive GAD-antibodies and at least one
      additional autoantibody and not yet diabetes.

      Objectives:

      DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset
      of type 1 diabetes.

      The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1
      diabetes.

      The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process
      leading to clinical type 1 diabetes in children with ongoing persistent beta-cell
      autoimmunity as indicated by multiple positive islet cell autoantibodies.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Children from four (4) years of age and participating in DiPiS, TEDDY or Trial Net.

          2. Positive GAD65Ab and at least one additional type 1 diabetes-associated autoantibody
             (IA-2Ab, ZnT8R/W/QAb or IAA).

          3. Written informed consent from the child and the child's parents or legal acceptable
             representative(s) according to local regulations.

        Exclusion Criteria:

          1. Ongoing treatment with immunosuppressant therapy (topical or inhaled steroids are
             accepted).

          2. Diabetes.

          3. Treatment with any oral or injected anti-diabetic medications.

          4. Significantly abnormal hematology results at screening.

          5. Clinically significant history of acute reaction to vaccines or other drugs.

          6. Treatment with any vaccine, other than influenza, within one month prior to the first
             dose of the study drug or planned treatment with vaccine up to two months after the
             last injection with the study drug.

          7. A history of epilepsy, serious head trauma or cerebrovascular accident, or clinical
             features of continuous motor unit activity in proximal muscles.

          8. Participation in other clinical trials with a new chemical entity within the previous
             3 months.

          9. Significant illness other than diabetes within 2 weeks prior to first dosing.

         10. Known human deficiency virus (HIV) or hepatitis.

         11. Presence of associated serious disease or condition, including active skin infections
             that preclude subcutaneous injection, which in the opinion of the investigators makes
             the patient non-eligible for the study.

         12. Diabetes-protective HLA-DQ6-genotype.