Overview

This trial is active, not recruiting.

Condition diabetes mellitus, type 1
Treatments gad-alum, vitamin d, etanercept
Phase phase 2
Sponsor Johnny Ludvigsson
Collaborator Swedish Child Diabetes Foundation
Start date May 2015
End date November 2018
Trial size 20 participants
Trial identifier NCT02464033, EDCR IIa

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
All patients will from Day 1 receive 2 000 IU vitamin D per os per day during 15 months, and from Days 1-90 receive etanercept (Enbrel) injected subcutaneously 0.8 mg/kg body weight (max 50 mg) once a week, and receive 2 subcutaneous injections of 20 μg Diamyd in a prime-and-boost regimen on Days 30 and 60.
gad-alum Diamyd
vitamin d
etanercept

Primary Outcomes

Measure
Reactions of the injection site as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period)
time frame: 6 months
To Evaluate the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period)
time frame: 6 months
Number of adverse events and number of participants with adverse events as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period)
time frame: 6 months
Number of serious adverse events and number of participants with serious adverse events as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period)
time frame: 6 months
Physical examinations, including neurological assessments as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period)
time frame: 6 months
Laboratory measurements as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period)
time frame: 6 months
GAD65AB titer measured to Evaluate the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period)
time frame: 6 months

Secondary Outcomes

Measure
Change in immune system markers from baseline to Month 6 (main study period) and subsequent visits during the extension study period
time frame: 6 months, 9, 15 and 30 months
C-peptide: Area Under the Curve (mean 0-120 min) during an MMTT, change from baseline
time frame: 6 months, 9, 15 and 30 months
Proportion of patients with a stimulated maximum C-peptide level above 0.2 nmol/L
time frame: 6 months, 9, 15 and 30 months
Hemoglobin A1c (HbA1c), change from baseline
time frame: 6 months, 9, 15 and 30 months
Exogenous insulin dose per kg body weight and 24 hours, change from baseline
time frame: 6 months, 9, 15 and 30 months
C-peptide: Fasting, 90 minute value, change from baseline
time frame: 6 months, 9, 15 and 30 months

Eligibility Criteria

Male or female participants from 8 years up to 18 years old.

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 norestisteron), 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. 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 doublestranded DNA antibody positivity 28. Arrhythmia 29. Pancreatitis 30. Vitamin D serum levels >100 nmol/L at screening

Additional Information

Official title 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
Principal investigator Johnny Ludvigsson, MD,PhD,Prof
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Linkoeping University.