EDCR Study - Etanercept Diamyd Combination Regimen -Open Trial to Evaluate Safety in Children With Type 1 Diabetes
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: GAD-Alum; Vitamin D; Etanercept
Intervention description: Recombinant Human Glutamic Acid Decarboxylase (rhGAD65)
Intervention MeSH terms: Vitamin D; Cholecalciferol; Etanercept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 8 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Diamyd; Diabetes; Juvenile Diabetes; Diabetes Type 1; Type 1 Diabetes; Autoimmune Diabetes; Insulin Dependent Diabetes; Type 1 Diabetes MellitusType 1 Diabetes Mellitus; rhGAD65; GAD65; GAD-Alum; Diabetes Mellitus; Diabetes mellitus Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Vitamin D; Etanercept

Summary:

      The objectives of this study is to:

        -  Evaluate the tolerability of a combination therapy with Diamyd, vitamin D and etanercept

        -  Evaluate how the above mentioned treatments influence the immune system and endogenous
           insulin secretion
    

Eligibility criteria:

        Inclusion Criteria:

          1. Informed consent given by patients and parent(s)/legal guardian(s)

          2. Type 1 diabetes according to the ADA classification, diagnosed within the previous 100
             days at the time of screening

          3. Age 8.00 -17.99 years at time of screening

          4. Fasting C-peptide at time of screening ≥0.12 nmol/L

          5. Positive for GADA but < 50 000 Units

          6. Menarchal females must agree to avoid pregnancy and have a negative urine pregnancy
             test

          7. Immunity against Varicella, either through previous infection or vaccination

          8. Patients must follow the Swedish vaccination programme

          9. Patients of childbearing potential must agree to using adequate contraception, if
             sexually active, until 1 year after the last administration of GAD-alum and
             etanercept. Adequate contraception is as follows:

        For females of childbearing potential:

          1. oral (except low-dose gestagen (lynestrenol and norethisterone), injectable, or
             implanted hormonal contraceptives (females)

          2. intrauterine device (females)

          3. intrauterine system (for example, progestin-releasing coil) (females)

          4. vasectomized male (with appropriate postvasectomy documentation of the absence of
             sperm in the ejaculate)

        For males of childbearing potential:

        a. Condom (male)

        Exclusion Criteria:

          1. Previous or current treatment with immunosuppressant therapy (although topical or
             inhaled steroids are accepted)

          2. Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of
             headache or in connection with fever a few days will be accepted)

          3. Treatment with any oral or injected anti-diabetic medications (especially hypoglycemic
             agents) other than insulin

          4. Treatment with Vitamin D, marketed or not, or unwilling to abstain from such
             medication during the trial

          5. A history of hypercalcemia

          6. A history of anaemia or significantly abnormal haematology results at screening

          7. A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features
             of continuous motor unit activity in proximal muscles

          8. Clinically significant history of acute reaction to vaccines or other drugs in the
             past

          9. Treatment with any vaccine within 4 months prior to planned first administration of
             GAD-Alum or planned treatment with vaccine up to 4 months after the last injection
             with GAD-Alum, including influenza vaccine

         10. Participation in other clinical trials with a new chemical entity within the previous
             3 months

         11. Inability or unwillingness to comply with the provisions of this protocol

         12. A history of alcohol or drug abuse

         13. A significant illness other than diabetes within 2 weeks prior to first dosing

         14. Known human immunodeficiency virus (HIV)

         15. Prior or active viral hepatitis B or C infection

         16. Females who are lactating or pregnant (for females who have started menstruating the
             possibility of pregnancy must be excluded by urine βHCG on-site within 24 hours prior
             to the GAD-Alum and etanercept administration, respectively)

         17. Males or females not willing to use adequate contraception, if sexually active, until
             1 year after the last GAD-Alum and etanercept administration, respectively

         18. Presence of associated serious disease or condition, including active skin infections
             that preclude subcutaneous injection, which in the opinion of the investigator makes
             the patient non-eligible for the study.

         19. Deemed by the investigator not being able to follow instructions and/or follow the
             study protocol

         20. Active infection, including chronic and local infection or a history of previous
             tendency to serious infections, recent or ongoing uncontrolled bacterial, viral,
             fungal or other opportunistic infections, or known infection with active EBV or CMV

         21. Hypersensitivity to the active substance in Enbrel (etanercept) or other ingredients
             in Enbrel

         22. Active or inactive (latent) tuberculosis (TBC) at screening

         23. History of malignancy or significant cardiovascular disease

         24. Current or history of leukopenia, anemia and/or thrombocytopenia

         25. Liver disease (clinical or hepatic enzymes >3 times the upper limit of normal (ULN))

         26. Renal insufficiency (clinical or creatinine >3 times the upper limit of normal (ULN))

         27. MS, undefined neurologic condition or known SLE, or anti-nuclear or known
             doublestranded DNA antibody positivity

         28. Arrhythmia

         29. Pancreatitis

         30. Vitamin D serum levels >100 nmol/L at screening