Newly diagnosed Type 1 diabetes (within 100 days) MedDRA version: 17.1 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: Diamyd
Product Code: rhGAD65 formulated in alum (GAD-alum)
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: No INN propo
Diamyd
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: range
Concentration number: 30-50
Trade Name: Enbrel 25 mg
Sponsors
Linköping University
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 ßHCG 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. Hypersensivity 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 thrombocytopeni 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 double-stranded DNA antibody positivity 28. Arrh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the tolerability of a combination therapy with Diamyd, vitamin D and etanercept;Secondary Objective: Evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion; Primary end point(s): Primary endpoints: To Evaluate the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period), 9, 15 and 30 (extension study period) Variables to evaluate tolerability: • Reactions of the injection site • Infections • Occurrence of Adverse Events (AEs) • Occurrence of Serious Adverse Events • Physiological and Neurology assessments • Laboratory measurments (biochemistry and haematology), including Calcium and Vitamin D in serum • GAD65AB titer (GADA) ;Timepoint(s) of evaluation of this end point: Month 6, 15 and 30 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: To evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion at at Month 6 (main study Period), 9, 15 and 30 (extension study period) Variables to evaluate the influence on the immune system: • Inflammatory markers, especially TNF-alfa, IL-1 beta, IL-2, IL-17 • Th2-deviation of cell-mediated immune response seen e.g. as increased ratio of IL-5,10, 13 in comparison with IFN-gamma, TNF-alfa, IL-1 beta and IL-17 • Increase of T-regulatory cells Variables to evaluate the effect of endogenous insulin secretion: • C-peptide (90 minute value and AUCmean 0-120 min) during an MMTT • Proportion of patients with a stimulated maximum C-peptide level above 0.2 nmol/L • Fasting C-peptide • Hemoglobin A1c (HbA1c) • Exogenous insulin dose per kg body weight and 24 hours ;Timepoint(s) of evaluation of this end point: Month 6, 15 and 30 | — |
Countries
Sweden
Contacts
Public ContactJohnny Ludvigsson
Linköping University
Outcome results
None listed