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

Inclusion criteria

• Informed consent given by patients and parent(s)/legal guardian(s)
• Type 1 diabetes according to the ADA classification, diagnosed within the previous 100 days at the time of screening
• Age 8.00 -17.99 years at time of screening
• Fasting C-peptide at time of screening ≥0.12 nmol/L
• Positive for GADA but < 50 000 Units
• Menarchal females must agree to avoid pregnancy and have a negative urine pregnancy test
• Immunity against Varicella, either through previous infection or vaccination
• Patients must follow the Swedish vaccination programme
• 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:

• oral (except low-dose gestagen (lynestrenol and norethisterone), injectable, or implanted hormonal contraceptives (females)
• intrauterine device (females)
• intrauterine system (for example, progestin-releasing coil) (females)
• vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate)

For males of childbearing potential:

a. Condom (male)

Exclusion criteria

• Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
• Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
• Treatment with any oral or injected anti-diabetic medications (especially hypoglycemic agents) other than insulin
• Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial
• A history of hypercalcemia
• A history of anaemia or significantly abnormal haematology results at screening
• A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles
• Clinically significant history of acute reaction to vaccines or other drugs in the past
• 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
• Participation in other clinical trials with a new chemical entity within the previous 3 months
• Inability or unwillingness to comply with the provisions of this protocol
• A history of alcohol or drug abuse
• A significant illness other than diabetes within 2 weeks prior to first dosing
• Known human immunodeficiency virus (HIV)
• Prior or active viral hepatitis B or C infection
• 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)
• Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last GAD-Alum and etanercept administration, respectively
• 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.
• Deemed by the investigator not being able to follow instructions and/or follow the study protocol
• 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
• Hypersensitivity to the active substance in Enbrel (etanercept) or other ingredients in Enbrel
• Active or inactive (latent) tuberculosis (TBC) at screening
• History of malignancy or significant cardiovascular disease
• Current or history of leukopenia, anemia and/or thrombocytopenia
• Liver disease (clinical or hepatic enzymes >3 times the upper limit of normal (ULN))
• Renal insufficiency (clinical or creatinine >3 times the upper limit of normal (ULN))
• MS, undefined neurologic condition or known SLE, or anti-nuclear or known doublestranded DNA antibody positivity
• Arrhythmia
• Pancreatitis
• Vitamin D serum levels >100 nmol/L at screening