Clinical trial NCT02464033: EDCR Study - Etanercept Diamyd Combination Regimen -Open Trial to Evaluate Safety in Children With Type 1 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
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
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
Collaborators: name: Swedish Child Diabetes Foundation
name: Ostergotland County Council, Sweden
name: Diamyd Medical AB
First posted: 2015-06-08
Enrollment: 20
Sex: ALL
Minimum age (years): 8
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability
timeFrame: 1 months
measure: Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability
timeFrame: 2 months
measure: Number of Patients With Any Abnormal Findings From Physical Examinations After Baseline
timeFrame: Month 1, 2, 3, 6, 9, 15 and 30
measure: Number of Patients With Clinically Significant Laboratory Findings
timeFrame: Month 1, 2, 3, 6, 9, 15 and 30
measure: GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)
timeFrame: 6 months
measure: GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)
timeFrame: 15 months
measure: GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)
timeFrame: 30 months
measure: Number of Patients With an Infection Reported as Adverse Event Related to Study Treatment
timeFrame: Month 1, 2, 3, 6, 9, 15 and 30
Secondary outcomes:
measure: C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline
timeFrame: Baseline and 6 months at 0, 30, 60, 90 and 120 minutes post-dose
measure: C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline
timeFrame: Baseline and 15 months at 0, 30, 60, 90 and 120 minutes post-dose
measure: C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline
timeFrame: Baseline and 30 months at 0, 30, 60, 90 and 120 minutes post-dose
measure: Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L
timeFrame: 6 months
measure: Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L
timeFrame: 15 months
measure: Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L
timeFrame: 30 months
measure: Hemoglobin A1c (HbA1c), Change From Baseline
timeFrame: Baseline and 6 months
measure: Hemoglobin A1c (HbA1c), Change From Baseline
timeFrame: Baseline and 15 months
measure: Hemoglobin A1c (HbA1c), Change From Baseline
timeFrame: Baseline and 30 months
measure: Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline
timeFrame: Baseline and 6 months
measure: Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline
timeFrame: Baseline and 15 months
measure: Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline
timeFrame: Baseline and 30 months
measure: C-peptide: Stimulated, 90 Minute Value, Change From Baseline
timeFrame: Baseline and 6 months
measure: C-peptide: Stimulated, 90 Minute Value, Change From Baseline
timeFrame: Baseline and 15 months
measure: C-peptide: Stimulated, 90 Minute Value, Change From Baseline
timeFrame: Baseline and 30 months
measure: C-peptide Fasting Concentration, Change From Baseline
timeFrame: Baseline and 6 months
measure: C-peptide Fasting Concentration, Change From Baseline
timeFrame: Baseline and 15 months
measure: C-peptide Fasting Concentration, Change From Baseline
timeFrame: Baseline and 30 months
measure: Spontaneous IL-17a Secretion
timeFrame: Baseline, 6 months, 9 months, 15 months and 30 months
measure: GAD65-induced IL-4 Secretion
timeFrame: Baseline, 6 months, 9 months, 15 months, 30 months
measure: GAD65-induced IL-13 Secretion
timeFrame: Baseline, 6 months, 9 months, 15 months, 30 months
measure: GAD65-induced IFN-gamma Secretion
timeFrame: Baseline, 6 months, 9 months, 15 months, 30 months
measure: GAD65-induced TNF-alpha Secretion
timeFrame: Baseline, 6 months, 9 months, 15 months, 30 months
measure: GAD65-induced GM-CSF Secretion
timeFrame: Baseline, 6 months, 9 months, 15 months, 30 months
measure: GAD65-induced MIP-1b Secretion
timeFrame: Baseline, 6 months, 9 months, 15 months, 30 months
measure: GAD65-induced MCP-1 Secretion
timeFrame: Baseline, 6 months, 9 months, 15 months, 30 months
Other outcomes:
Locations:
city: Helsingborg
country: Sweden
facility: Helsingborg Hospital
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Lund
country: Sweden
facility: Lund University Hospital
city: Malmö
country: Sweden
facility: Skåne University Hospital, UMAS
city: Stockholm
country: Sweden
facility: Sachsska, Södersjukhuset
city: Uddevalla
country: Sweden
facility: Uddevalla Hospital
city: Västerås
country: Sweden
facility: Västerås Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
Study officials:
affiliation: Linkoeping University
name: Johnny Ludvigsson, MD,PhD,Prof
role: PRINCIPAL_INVESTIGATOR
References: