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

Johnny Ludvigsson20 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 1

Interventions

GAD-AlumDRUG

Recombinant Human Glutamic Acid Decarboxylase (rhGAD65)

Vitamin DDRUG

EtanerceptDRUG

Eligibility

Sex: ALLMin age: 8 YearsMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (8)

Helsingborg Hospital

Helsingborg, Sweden

Linköping University Hospital

Linköping, Sweden

Lund University Hospital

Lund, Sweden

Skåne University Hospital, UMAS

Malmo, Sweden

Outcomes

Primary Outcomes

Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability

Number of patients with reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching, Other). Inspection of injection site 60 minutes after GAD-Alum injection by investigator or nurse

Time frame: 1 months

Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability

Time frame: 2 months

Number of Patients With Any Abnormal Findings From Physical Examinations After Baseline

Number of patients with any abnormal findings from physical examinations after baseline, including neurological assessments as an assessment of tolerability.

Time frame: Month 1, 2, 3, 6, 9, 15 and 30

Number of Patients With Clinically Significant Laboratory Findings

Number of patients with clinically significant laboratory findings, laboratory measurements as an assessment of the tolerability

Time frame: Month 1, 2, 3, 6, 9, 15 and 30

GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)

GAD65AB titer (GADA) change from baseline. GAD65AB = Antibodies to GAD with molecular mass 65000

Time frame: 6 months

GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)

GAD65AB titer (GADA) change from baseline. GAD65AB = Antibodies to GAD with molecular mass 65000

Time frame: 15 months

GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)

Data from ClinicalTrials.gov

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Secondary Outcomes

C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline

Weighted mean C-peptide: (AUC mean 0-120 min) during an MMTT, change from baseline to 6 months. MMTT=Mixed Meal Tolerance Test

Time frame: Baseline and 6 months at 0, 30, 60, 90 and 120 minutes post-dose

C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline

Weighted mean C-peptide: (AUC mean 0-120 min) during an MMTT, change from baseline to 15 months

Time frame: Baseline and 15 months at 0, 30, 60, 90 and 120 minutes post-dose

C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline

Weighted mean C-peptide: (AUC mean 0-120 min) during an MMTT, change from baseline to 30 months

Time frame: Baseline and 30 months at 0, 30, 60, 90 and 120 minutes post-dose

Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L

Number of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at 6 months

Time frame: 6 months

Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L

Number of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at 15 months

Time frame: 15 months

Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L

Number of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at 30 months

Time frame: 30 months

Hemoglobin A1c (HbA1c), Change From Baseline

Hemoglobin A1c (HbA1c), change from baseline to 6 months

Time frame: Baseline and 6 months

Hemoglobin A1c (HbA1c), Change From Baseline

Hemoglobin A1c (HbA1c), change from baseline to 15 months

Time frame: Baseline and 15 months

Hemoglobin A1c (HbA1c), Change From Baseline

Hemoglobin A1c (HbA1c), change from baseline to 30 months

Time frame: Baseline and 30 months

Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline

Exogenous 24-hour insulin dose per kg body weight and 24 hours average, change from baseline

Time frame: Baseline and 6 months

Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline

Exogenous 24-hour insulin dose per kg body weight and 24 hours average, change from baseline

Time frame: Baseline and 15 months

Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline

Exogenous 24-hour insulin dose per kg body weight and 24 hours average, change from baseline

Time frame: Baseline and 30 months

C-peptide: Stimulated, 90 Minute Value, Change From Baseline

C-peptide: Stimulated, 90 minute value, change from baseline to 6 months

Time frame: Baseline and 6 months

C-peptide: Stimulated, 90 Minute Value, Change From Baseline

C-peptide: Stimulated, 90 minute value, change from baseline to 15 months

Time frame: Baseline and 15 months

C-peptide: Stimulated, 90 Minute Value, Change From Baseline

C-peptide: Stimulated, 90 minute value, change from baseline to 30 months

Time frame: Baseline and 30 months

C-peptide Fasting Concentration, Change From Baseline

C-peptide: Fasting concentration, change from baseline to 6 months

Time frame: Baseline and 6 months

C-peptide Fasting Concentration, Change From Baseline

C-peptide: Fasting, concentration, change from baseline to 15 months

Time frame: Baseline and 15 months

C-peptide Fasting Concentration, Change From Baseline

C-peptide: Fasting, concentration, change from baseline to 30 months

Time frame: Baseline and 30 months

Spontaneous IL-17a Secretion

Spontaneous IL-17a secretion at baseline, 6 months, 9 months, 15 months and 30 months

Time frame: Baseline, 6 months, 9 months, 15 months and 30 months

GAD65-induced IL-4 Secretion

GAD65-induced IL-4 secretion at baseline, 6 months, 9 months, 15 months, 30 months