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

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

Sponsors

Lead Sponsor: Johnny Ludvigsson

Collaborator: Swedish Child Diabetes Foundation
Ostergotland County Council, Sweden
Diamyd Medical AB

Source Linkoeping University
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

Overall Status Completed
Start Date May 2015
Completion Date February 25, 2019
Primary Completion Date February 25, 2019
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability 1 months
Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability 2 months
Number of Patients With Any Abnormal Findings From Physical Examinations After Baseline Month 1, 2, 3, 6, 9, 15 and 30
Number of Patients With Clinically Significant Laboratory Findings Month 1, 2, 3, 6, 9, 15 and 30
GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period) 6 months
GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period) 15 months
GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period) 30 months
Number of Patients With an Infection Reported as Adverse Event Related to Study Treatment Month 1, 2, 3, 6, 9, 15 and 30
Secondary Outcome
Measure Time Frame
C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline 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 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 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 6 months
Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L 15 months
Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L 30 months
Hemoglobin A1c (HbA1c), Change From Baseline Baseline and 6 months
Hemoglobin A1c (HbA1c), Change From Baseline Baseline and 15 months
Hemoglobin A1c (HbA1c), Change From Baseline Baseline and 30 months
Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline Baseline and 6 months
Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline Baseline and 15 months
Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline Baseline and 30 months
C-peptide: Stimulated, 90 Minute Value, Change From Baseline Baseline and 6 months
C-peptide: Stimulated, 90 Minute Value, Change From Baseline Baseline and 15 months
C-peptide: Stimulated, 90 Minute Value, Change From Baseline Baseline and 30 months
C-peptide Fasting Concentration, Change From Baseline Baseline and 6 months
C-peptide Fasting Concentration, Change From Baseline Baseline and 15 months
C-peptide Fasting Concentration, Change From Baseline Baseline and 30 months
Change in Immune System Markers From Baseline to Month 6 (Main Study Period) and Subsequent Visits During the Extension Study Period Baseline and 6, 9, 15 and 30 months
Enrollment 20
Condition
Intervention

Intervention Type: Drug

Intervention Name: GAD-Alum

Description: Recombinant Human Glutamic Acid Decarboxylase (rhGAD65)

Arm Group Label: A

Other Name: Diamyd

Intervention Type: Drug

Intervention Name: Vitamin D

Arm Group Label: A

Other Name: Cholecalciferol

Intervention Type: Drug

Intervention Name: Etanercept

Arm Group Label: A

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

Gender: All

Minimum Age: 8 Years

Maximum Age: 18 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Johnny Ludvigsson, MD,PhD,Prof Principal Investigator Linkoeping University
Location
Facility:
Helsingborg Hospital | Helsingborg, Sweden
Linköping University Hospital | Linköping, Sweden
Lund University Hospital | Lund, Sweden
Skåne University Hospital, UMAS | Malmö, Sweden
Sachsska, Södersjukhuset | Stockholm, Sweden
Uddevalla Hospital | Uddevalla, Sweden
Västerås Hospital | Västerås, Sweden
Örebro University Hospital | Örebro, Sweden
Location Countries

Sweden

Verification Date

September 2019

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Linkoeping University

Investigator Full Name: Johnny Ludvigsson

Investigator Title: MD, PhD, Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: A

Type: Experimental

Description: 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.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov