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

• ClinicalTrials.gov Identifier: NCT02464033
• Recruitment Status: Completed
• First Posted: June 8, 2015
• Results First Posted: September 25, 2019
• Last Update Posted: March 29, 2021
• Sponsor: Johnny Ludvigsson
• Collaborators: Swedish Child Diabetes Foundation; Ostergotland County Council, Sweden; Diamyd Medical AB
• Information provided by (Responsible Party): Johnny Ludvigsson, Linkoeping University

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 1
• Interventions: Drug: GAD-Alum; Drug: Vitamin D; Drug: Etanercept
• Enrollment: 20

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Period Title: Overall Study
Started	20
Completed	20
Not Completed	0

Baseline Characteristics

Arm/Group Title		GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
Overall Number of Baseline Participants		20
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants
	<=18 years	20 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	20 participants
		12.36 (2.321)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants
	Female	7 35.0%
	Male	13 65.0%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Sweden	Number Analyzed	20 participants
		20
Type 1 Diabetes duration; Mean (Standard Deviation); Unit of measure: Days
	Number Analyzed	20 participants
		81.35 (22.091)
Body Mass Index; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	20 participants
		18.38 (2.141)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Measure Type: Count of Participants; Unit of Measure: Participants
	3 15.0%

2. Primary Outcome

Title	Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability
Description	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	2 months

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Measure Type: Count of Participants; Unit of Measure: Participants
	5 25.0%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Measure Type: Count of Participants; Unit of Measure: Participants
	6 30.0%

4. Primary Outcome

Title	Number of Patients With Clinically Significant Laboratory Findings
Description	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

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

5. Primary Outcome

Title	GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)
Description	GAD65AB titer (GADA) change from baseline. GAD65AB = Antibodies to GAD with molecular mass 65000
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Intention To Treat (ITT)

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: U/mL
	2509.41 (4866.515)

6. Primary Outcome

Title	GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)
Description	GAD65AB titer (GADA) change from baseline. GAD65AB = Antibodies to GAD with molecular mass 65000
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: U/mL
	1036.19 (2527.249)

7. Primary Outcome

Title	GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)
Description	GAD65AB titer (GADA) change from baseline. GAD65AB = Antibodies to GAD with molecular mass 65000
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: U/mL
	347.01 (1564.466)

8. Primary Outcome

Title	Number of Patients With an Infection Reported as Adverse Event Related to Study Treatment
Description	Number of patients with an infection reported as Adverse Event related to study treatment (GAD-Alum and/or Etanercept),as an assessment of the tolerability
Time Frame	Month 1, 2, 3, 6, 9, 15 and 30

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Measure Type: Count of Participants; Unit of Measure: Participants
	3 15.0%

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT, MMTT not performed for 2 patients hence no data available for 2 out of the 20 patients

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: nmol/L*min
	-0.09 (0.153)

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: nmol/L*min
	-0.30 (0.158)

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT, , MMTT not performed for 1 patient hence no data available for 1 out of the 20 patients

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: nmol/L*min
	-0.40 (0.168)

12. Secondary Outcome

Title	Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L
Description	Number of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Measure Type: Count of Participants; Unit of Measure: Participants
	17 85.0%

13. Secondary Outcome

Title	Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L
Description	Number of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at 15 months
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Measure Type: Count of Participants; Unit of Measure: Participants
	14 70.0%

14. Secondary Outcome

Title	Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L
Description	Number of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at 30 months
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Measure Type: Count of Participants; Unit of Measure: Participants
	8 40.0%

15. Secondary Outcome

Title	Hemoglobin A1c (HbA1c), Change From Baseline
Description	Hemoglobin A1c (HbA1c), change from baseline to 6 months
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: mmol/mol
	0.80 (8.433)

16. Secondary Outcome

Title	Hemoglobin A1c (HbA1c), Change From Baseline
Description	Hemoglobin A1c (HbA1c), change from baseline to 15 months
Time Frame	Baseline and 15 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: mmol/mol
	6.15 (12.495)

17. Secondary Outcome

Title	Hemoglobin A1c (HbA1c), Change From Baseline
Description	Hemoglobin A1c (HbA1c), change from baseline to 30 months
Time Frame	Baseline and 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: mmol/mol
	7.55 (11.213)

18. Secondary Outcome

Title	Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline
Description	Exogenous 24-hour insulin dose per kg body weight and 24 hours average, change from baseline
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: IU
	0.01 (0.249)

19. Secondary Outcome

Title	Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline
Description	Exogenous 24-hour insulin dose per kg body weight and 24 hours average, change from baseline
Time Frame	Baseline and 15 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: IU
	0.25 (0.342)

20. Secondary Outcome

Title	Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline
Description	Exogenous 24-hour insulin dose per kg body weight and 24 hours average, change from baseline
Time Frame	Baseline and 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: IU
	0.42 (0.333)

21. Secondary Outcome

Title	C-peptide: Stimulated, 90 Minute Value, Change From Baseline
Description	C-peptide: Stimulated, 90 minute value, change from baseline to 6 months
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT, not performed for 2 patients hence no data available for 2 out of the 20 patients

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: nmol/L
	-0.09 (0.233)

22. Secondary Outcome

Title	C-peptide: Stimulated, 90 Minute Value, Change From Baseline
Description	C-peptide: Stimulated, 90 minute value, change from baseline to 15 months
Time Frame	Baseline and 15 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: nmol/L
	-0.35 (0.231)

23. Secondary Outcome

Title	C-peptide: Stimulated, 90 Minute Value, Change From Baseline
Description	C-peptide: Stimulated, 90 minute value, change from baseline to 30 months
Time Frame	Baseline and 30 months

Outcome Measure Data

Analysis Population Description

ITT, not performed for 1 patient hence no data available for 1 out of the 20 patients

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: nmol/L
	-0.49 (0.221)

24. Secondary Outcome

Title	C-peptide Fasting Concentration, Change From Baseline
Description	C-peptide: Fasting concentration, change from baseline to 6 months
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: nmol/L
	-0.02 (0.083)

25. Secondary Outcome

Title	C-peptide Fasting Concentration, Change From Baseline
Description	C-peptide: Fasting, concentration, change from baseline to 15 months
Time Frame	Baseline and 15 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: nmol/L
	-0.10 (0.091)

26. Secondary Outcome

Title	C-peptide Fasting Concentration, Change From Baseline
Description	C-peptide: Fasting, concentration, change from baseline to 30 months
Time Frame	Baseline and 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group Description:	All patients will from Day 1 receive 2000 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 Vitamin D Etanercept
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: nmol/L
	-0.15 (0.093)

27. Secondary Outcome

Title	Spontaneous IL-17a Secretion
Description	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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title		GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
Overall Number of Participants Analyzed		20
Median (Standard Deviation); Unit of Measure: pg/ml
IL-17a, Baseline	Number Analyzed	20 participants
		3.16 (8.36)
IL-17a, 6 months	Number Analyzed	19 participants
		6.07 (10.13)
IL-17a, 9 months	Number Analyzed	20 participants
		7.06 (11.35)
IL-17a,15 months	Number Analyzed	18 participants
		6.54 (7.83)
IL-17a, 30 months	Number Analyzed	18 participants
		4.75 (10.64)

28. Secondary Outcome

Title	GAD65-induced IL-4 Secretion
Description	GAD65-induced IL-4 secretion at baseline, 6 months, 9 months, 15 months, 30 months
Time Frame	Baseline, 6 months, 9 months, 15 months, 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title		GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
Overall Number of Participants Analyzed		20
Median (Standard Deviation); Unit of Measure: pg/ml
IL-4, baseline	Number Analyzed	20 participants
		0.01 (1.03)
IL-4, 6 months	Number Analyzed	20 participants
		0.01 (0.58)
IL-4, 9 months	Number Analyzed	19 participants
		0.01 (1.21)
IL-4, 15 months	Number Analyzed	18 participants
		0.01 (1.52)
IL-4, 30 months	Number Analyzed	18 participants
		0.01 (0.63)

29. Secondary Outcome

Title	GAD65-induced IL-13 Secretion
Description	GAD65-induced IL-13 secretion at baseline, 6 months, 9 months, 15 months, 30 months
Time Frame	Baseline, 6 months, 9 months, 15 months, 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title		GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
Overall Number of Participants Analyzed		20
Median (Standard Deviation); Unit of Measure: pg/ml
IL-13, Baseline	Number Analyzed	20 participants
		0.01 (56.88)
IL-13, 6 months	Number Analyzed	19 participants
		1.67 (58.47)
IL-13, 9 months	Number Analyzed	20 participants
		5.12 (69.63)
IL-13, 15 months	Number Analyzed	18 participants
		0.01 (99.00)
IL-13, 30 months	Number Analyzed	20 participants
		0.01 (49.95)

30. Secondary Outcome

Title	GAD65-induced IFN-gamma Secretion
Description	GAD65-induced IFN-gamma secretion at baseline, 6 months, 9 months, 15 months, 30 months
Time Frame	Baseline, 6 months, 9 months, 15 months, 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title		GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
Overall Number of Participants Analyzed		20
Median (Standard Deviation); Unit of Measure: pg/ml
IFN-gamma, baseline	Number Analyzed	20 participants
		4.39 (210.52)
IFN-gamma, 6 months	Number Analyzed	19 participants
		11.44 (223.16)
IFN-gamma, 9 months	Number Analyzed	19 participants
		22.77 (679.35)
IFN-gamma, 15 months	Number Analyzed	18 participants
		0.01 (1679.59)
IFN-gamma, 30 months	Number Analyzed	18 participants
		0.01 (227.91)

31. Secondary Outcome

Title	GAD65-induced TNF-alpha Secretion
Description	GAD65-induced TNF-alpha secretion at baseline, 6 months, 9 months, 15 months, 30 months
Time Frame	Baseline, 6 months, 9 months, 15 months, 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title		GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
Overall Number of Participants Analyzed		20
Median (Standard Deviation); Unit of Measure: pg/ml
TNF-alpha, baseline	Number Analyzed	20 participants
		0.01 (348.28)
TNF-alpha, 6 months	Number Analyzed	19 participants
		0.01 (89.19)
TNF-alpha, 9 months	Number Analyzed	19 participants
		0.01 (355.09)
TNF-alpha, 15 months	Number Analyzed	18 participants
		0.01 (362.35)
TNF-alpha, 30 months	Number Analyzed	18 participants
		0.01 (206.37)

32. Secondary Outcome

Title	GAD65-induced GM-CSF Secretion
Description	GAD65-induced GM-CSF secretion baseline, 6 months, 9 months, 15 months, 30 months
Time Frame	Baseline, 6 months, 9 months, 15 months, 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title		GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
Overall Number of Participants Analyzed		20
Median (Standard Deviation); Unit of Measure: pg/ml
GM-CSF, baseline	Number Analyzed	20 participants
		0.01 (16.96)
GM-CSF, 6 months	Number Analyzed	19 participants
		0.01 (18.00)
GM-CSF, 9 months	Number Analyzed	19 participants
		1.52 (24.70)
GM-CSF, 15 months	Number Analyzed	18 participants
		0.01 (36.95)
GM-CSF, 30 months	Number Analyzed	18 participants
		0.01 (6.00)

33. Secondary Outcome

Title	GAD65-induced MIP-1b Secretion
Description	GAD65-induced MIP-1b secretion at baseline, 6 months, 9 months, 15 months, 30 months
Time Frame	Baseline, 6 months, 9 months, 15 months, 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title		GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
Overall Number of Participants Analyzed		20
Median (Standard Deviation); Unit of Measure: pg/ml
MIP-1b, baseline	Number Analyzed	20 participants
		0.01 (85.46)
MIP-1b, 6 months	Number Analyzed	19 participants
		0.01 (57.78)
MIP-1b, 9 months	Number Analyzed	19 participants
		0.01 (134.30)
MIP-1b, 15 months	Number Analyzed	18 participants
		30.64 (302.04)
MIP-1b, 30 months	Number Analyzed	18 participants
		14.61 (72.54)

34. Secondary Outcome

Title	GAD65-induced MCP-1 Secretion
Description	GAD65-induced MCP-1 secretion at baseline, 6 months, 9 months, 15 months, 30 months
Time Frame	Baseline, 6 months, 9 months, 15 months, 30 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title		GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
Overall Number of Participants Analyzed		20
Median (Standard Deviation); Unit of Measure: pg/ml
MCP-1, baseline	Number Analyzed	20 participants
		0.01 (106.61)
MCP-1, 6 months	Number Analyzed	19 participants
		38.54 (89.74)
MCP-1, 9 months	Number Analyzed	19 participants
		0.01 (144.03)
MCP-1, 15 months	Number Analyzed	18 participants
		24.42 (203.74)
MCP-1, 30 months	Number Analyzed	18 participants
		37.50 (220.66)

Adverse Events

Time Frame	30 months
Adverse Event Reporting Description	Adverse Events were recorded in the Case Report Form at each clinic visit.
Arm/Group Title	GAD-Alum+Vitamin D+Etanercept
Arm/Group 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. GAD-Alum Vitamin D Etanercept
All-Cause Mortality
	GAD-Alum+Vitamin D+Etanercept
	Affected / at Risk (%)
Total	0/20 (0.00%)
Serious Adverse Events
	GAD-Alum+Vitamin D+Etanercept
	Affected / at Risk (%)	# Events
Total	0/20 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	GAD-Alum+Vitamin D+Etanercept
	Affected / at Risk (%)	# Events
Total	20/20 (100.00%)
Gastrointestinal disorders
Diarrhoea † 1	2/20 (10.00%)	2
General disorders
Injection site reaction † 1	13/20 (65.00%)	20
Pyrexia † 1	2/20 (10.00%)	2
Infections and infestations
Gastroenteritis † 1	9/20 (45.00%)	11
Influenza † 1	2/20 (10.00%)	2
Nasopharyngitis † 1	13/20 (65.00%)	30
Viral infection † 1	8/20 (40.00%)	15
Injury, poisoning and procedural complications
Ligament sprain † 1	2/20 (10.00%)	2
Psychiatric disorders
Depression † 1	2/20 (10.00%)	2
1 Term from vocabulary, MedDRA (22.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Johnny Ludvigsson, MD, PhD, Prof Linkoeping University
• Organization: Linkoeping University
• Phone: +46 13 28 68 54
• EMail: Johnny.Ludvigsson@liu.se

• Responsible Party: Johnny Ludvigsson, Linkoeping University
• ClinicalTrials.gov Identifier: NCT02464033
• Other Study ID Numbers: EDCR IIa
• First Submitted: May 19, 2015
• First Posted: June 8, 2015
• Results First Submitted: June 10, 2019
• Results First Posted: September 25, 2019
• Last Update Posted: March 29, 2021