EDCR Study - Etanercept Diamyd Combination Regimen -Open Trial to Evaluate Safety in Children With Type 1 Diabetes

Open Label Trial to Evaluate the Tolerability of a Combination Therapy Consisting of GAD-alum (Diamyd®), Etanercept and Vitamin D in Children and Adolescents Newly Diagnosed With Type 1 Diabetes

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

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