Trial Outcomes & Findings for EDCR Study - Etanercept Diamyd Combination Regimen -Open Trial to Evaluate Safety in Children With Type 1 Diabetes (NCT NCT02464033)

NCT ID: NCT02464033

Last Updated: 2021-03-29

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: 1 months
• Results posted on: 2021-03-29

Participant Flow

Participant milestones

Measure	GAD-Alum+Vitamin D+Etanercept 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 Study STARTED	20
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Age, Categorical <=18 years	20 Participants n=20 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=20 Participants
Age, Categorical >=65 years	0 Participants n=20 Participants
Age, Continuous	12.36 years STANDARD_DEVIATION 2.321 • n=20 Participants
Sex: Female, Male Female	7 Participants n=20 Participants
Sex: Female, Male Male	13 Participants n=20 Participants
Region of Enrollment Sweden	20 participants n=20 Participants
Type 1 Diabetes duration	81.35 days STANDARD_DEVIATION 22.091 • n=20 Participants
Body Mass Index	18.38 kg/m^2 STANDARD_DEVIATION 2.141 • n=20 Participants

PRIMARY outcome

Timeframe: 1 months

Population: Safety

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability	3 Participants

PRIMARY outcome

Timeframe: 2 months

Population: Safety

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability	5 Participants

PRIMARY outcome

Timeframe: Month 1, 2, 3, 6, 9, 15 and 30

Population: Safety

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Number of Patients With Any Abnormal Findings From Physical Examinations After Baseline	6 Participants

PRIMARY outcome

Timeframe: Month 1, 2, 3, 6, 9, 15 and 30

Population: Safety

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Number of Patients With Clinically Significant Laboratory Findings	0 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Intention To Treat (ITT)

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)	2509.41 U/mL Standard Deviation 4866.515

PRIMARY outcome

Timeframe: 15 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)	1036.19 U/mL Standard Deviation 2527.249

PRIMARY outcome

Timeframe: 30 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)	347.01 U/mL Standard Deviation 1564.466

PRIMARY outcome

Timeframe: Month 1, 2, 3, 6, 9, 15 and 30

Population: Safety

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Number of Patients With an Infection Reported as Adverse Event Related to Study Treatment	3 Participants

SECONDARY outcome

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

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

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=18 Participants 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
C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline	-0.09 nmol/L*min Standard Deviation 0.153

SECONDARY outcome

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

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline	-0.30 nmol/L*min Standard Deviation 0.158

SECONDARY outcome

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

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

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=19 Participants 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
C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline	-0.40 nmol/L*min Standard Deviation 0.168

SECONDARY outcome

Timeframe: 6 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L	17 Participants

SECONDARY outcome

Timeframe: 15 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L	14 Participants

SECONDARY outcome

Timeframe: 30 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L	8 Participants

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Hemoglobin A1c (HbA1c), Change From Baseline	0.80 mmol/mol Standard Deviation 8.433

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Hemoglobin A1c (HbA1c), Change From Baseline	6.15 mmol/mol Standard Deviation 12.495

SECONDARY outcome

Timeframe: Baseline and 30 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Hemoglobin A1c (HbA1c), Change From Baseline	7.55 mmol/mol Standard Deviation 11.213

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline	0.01 IU Standard Deviation 0.249

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline	0.25 IU Standard Deviation 0.342

SECONDARY outcome

Timeframe: Baseline and 30 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline	0.42 IU Standard Deviation 0.333

SECONDARY outcome

Timeframe: Baseline and 6 months

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

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=18 Participants 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
C-peptide: Stimulated, 90 Minute Value, Change From Baseline	-0.09 nmol/L Standard Deviation 0.233

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
C-peptide: Stimulated, 90 Minute Value, Change From Baseline	-0.35 nmol/L Standard Deviation 0.231

SECONDARY outcome

Timeframe: Baseline and 30 months

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

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=19 Participants 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
C-peptide: Stimulated, 90 Minute Value, Change From Baseline	-0.49 nmol/L Standard Deviation 0.221

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
C-peptide Fasting Concentration, Change From Baseline	-0.02 nmol/L Standard Deviation 0.083

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
C-peptide Fasting Concentration, Change From Baseline	-0.10 nmol/L Standard Deviation 0.091

SECONDARY outcome

Timeframe: Baseline and 30 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
C-peptide Fasting Concentration, Change From Baseline	-0.15 nmol/L Standard Deviation 0.093

SECONDARY outcome

Timeframe: Baseline, 6 months, 9 months, 15 months and 30 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
Spontaneous IL-17a Secretion IL-17a, Baseline	3.16 pg/ml Standard Deviation 8.36
Spontaneous IL-17a Secretion IL-17a, 6 months	6.07 pg/ml Standard Deviation 10.13
Spontaneous IL-17a Secretion IL-17a, 9 months	7.06 pg/ml Standard Deviation 11.35
Spontaneous IL-17a Secretion IL-17a,15 months	6.54 pg/ml Standard Deviation 7.83
Spontaneous IL-17a Secretion IL-17a, 30 months	4.75 pg/ml Standard Deviation 10.64

SECONDARY outcome

Timeframe: Baseline, 6 months, 9 months, 15 months, 30 months

Population: ITT

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

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65-induced IL-4 Secretion IL-4, baseline	0.01 pg/ml Standard Deviation 1.03
GAD65-induced IL-4 Secretion IL-4, 6 months	0.01 pg/ml Standard Deviation 0.58
GAD65-induced IL-4 Secretion IL-4, 9 months	0.01 pg/ml Standard Deviation 1.21
GAD65-induced IL-4 Secretion IL-4, 15 months	0.01 pg/ml Standard Deviation 1.52
GAD65-induced IL-4 Secretion IL-4, 30 months	0.01 pg/ml Standard Deviation 0.63

SECONDARY outcome

Timeframe: Baseline, 6 months, 9 months, 15 months, 30 months

Population: ITT

GAD65-induced IL-13 secretion at baseline, 6 months, 9 months, 15 months, 30 months

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65-induced IL-13 Secretion IL-13, Baseline	0.01 pg/ml Standard Deviation 56.88
GAD65-induced IL-13 Secretion IL-13, 6 months	1.67 pg/ml Standard Deviation 58.47
GAD65-induced IL-13 Secretion IL-13, 9 months	5.12 pg/ml Standard Deviation 69.63
GAD65-induced IL-13 Secretion IL-13, 15 months	0.01 pg/ml Standard Deviation 99.00
GAD65-induced IL-13 Secretion IL-13, 30 months	0.01 pg/ml Standard Deviation 49.95

SECONDARY outcome

Timeframe: Baseline, 6 months, 9 months, 15 months, 30 months

Population: ITT

GAD65-induced IFN-gamma secretion at baseline, 6 months, 9 months, 15 months, 30 months

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65-induced IFN-gamma Secretion IFN-gamma, baseline	4.39 pg/ml Standard Deviation 210.52
GAD65-induced IFN-gamma Secretion IFN-gamma, 6 months	11.44 pg/ml Standard Deviation 223.16
GAD65-induced IFN-gamma Secretion IFN-gamma, 9 months	22.77 pg/ml Standard Deviation 679.35
GAD65-induced IFN-gamma Secretion IFN-gamma, 15 months	0.01 pg/ml Standard Deviation 1679.59
GAD65-induced IFN-gamma Secretion IFN-gamma, 30 months	0.01 pg/ml Standard Deviation 227.91

SECONDARY outcome

Timeframe: Baseline, 6 months, 9 months, 15 months, 30 months

Population: ITT

GAD65-induced TNF-alpha secretion at baseline, 6 months, 9 months, 15 months, 30 months

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65-induced TNF-alpha Secretion TNF-alpha, baseline	0.01 pg/ml Standard Deviation 348.28
GAD65-induced TNF-alpha Secretion TNF-alpha, 6 months	0.01 pg/ml Standard Deviation 89.19
GAD65-induced TNF-alpha Secretion TNF-alpha, 9 months	0.01 pg/ml Standard Deviation 355.09
GAD65-induced TNF-alpha Secretion TNF-alpha, 15 months	0.01 pg/ml Standard Deviation 362.35
GAD65-induced TNF-alpha Secretion TNF-alpha, 30 months	0.01 pg/ml Standard Deviation 206.37

SECONDARY outcome

Timeframe: Baseline, 6 months, 9 months, 15 months, 30 months

Population: ITT

GAD65-induced GM-CSF secretion baseline, 6 months, 9 months, 15 months, 30 months

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65-induced GM-CSF Secretion GM-CSF, 9 months	1.52 pg/ml Standard Deviation 24.70
GAD65-induced GM-CSF Secretion GM-CSF, 15 months	0.01 pg/ml Standard Deviation 36.95
GAD65-induced GM-CSF Secretion GM-CSF, 30 months	0.01 pg/ml Standard Deviation 6.00
GAD65-induced GM-CSF Secretion GM-CSF, baseline	0.01 pg/ml Standard Deviation 16.96
GAD65-induced GM-CSF Secretion GM-CSF, 6 months	0.01 pg/ml Standard Deviation 18.00

SECONDARY outcome

Timeframe: Baseline, 6 months, 9 months, 15 months, 30 months

Population: ITT

GAD65-induced MIP-1b secretion at baseline, 6 months, 9 months, 15 months, 30 months

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65-induced MIP-1b Secretion MIP-1b, baseline	0.01 pg/ml Standard Deviation 85.46
GAD65-induced MIP-1b Secretion MIP-1b, 6 months	0.01 pg/ml Standard Deviation 57.78
GAD65-induced MIP-1b Secretion MIP-1b, 9 months	0.01 pg/ml Standard Deviation 134.30
GAD65-induced MIP-1b Secretion MIP-1b, 15 months	30.64 pg/ml Standard Deviation 302.04
GAD65-induced MIP-1b Secretion MIP-1b, 30 months	14.61 pg/ml Standard Deviation 72.54

SECONDARY outcome

Timeframe: Baseline, 6 months, 9 months, 15 months, 30 months

Population: ITT

GAD65-induced MCP-1 secretion at baseline, 6 months, 9 months, 15 months, 30 months

Outcome measures

Measure	GAD-Alum+Vitamin D+Etanercept n=20 Participants 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
GAD65-induced MCP-1 Secretion MCP-1, baseline	0.01 pg/ml Standard Deviation 106.61
GAD65-induced MCP-1 Secretion MCP-1, 6 months	38.54 pg/ml Standard Deviation 89.74
GAD65-induced MCP-1 Secretion MCP-1, 9 months	0.01 pg/ml Standard Deviation 144.03
GAD65-induced MCP-1 Secretion MCP-1, 15 months	24.42 pg/ml Standard Deviation 203.74
GAD65-induced MCP-1 Secretion MCP-1, 30 months	37.50 pg/ml Standard Deviation 220.66

Adverse Events

GAD-Alum+Vitamin D+Etanercept

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	GAD-Alum+Vitamin D+Etanercept n=20 participants at risk 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
Infections and infestations Gastroenteritis	45.0% 9/20 • Number of events 11 • 30 months Adverse Events were recorded in the Case Report Form at each clinic visit.
Infections and infestations Influenza	10.0% 2/20 • Number of events 2 • 30 months Adverse Events were recorded in the Case Report Form at each clinic visit.
Infections and infestations Nasopharyngitis	65.0% 13/20 • Number of events 30 • 30 months Adverse Events were recorded in the Case Report Form at each clinic visit.
Infections and infestations Viral infection	40.0% 8/20 • Number of events 15 • 30 months Adverse Events were recorded in the Case Report Form at each clinic visit.
Injury, poisoning and procedural complications Ligament sprain	10.0% 2/20 • Number of events 2 • 30 months Adverse Events were recorded in the Case Report Form at each clinic visit.
Psychiatric disorders Depression	10.0% 2/20 • Number of events 2 • 30 months Adverse Events were recorded in the Case Report Form at each clinic visit.
Gastrointestinal disorders Diarrhoea	10.0% 2/20 • Number of events 2 • 30 months Adverse Events were recorded in the Case Report Form at each clinic visit.
General disorders Injection site reaction	65.0% 13/20 • Number of events 20 • 30 months Adverse Events were recorded in the Case Report Form at each clinic visit.
General disorders Pyrexia	10.0% 2/20 • Number of events 2 • 30 months Adverse Events were recorded in the Case Report Form at each clinic visit.

Additional Information

Johnny Ludvigsson, MD, PhD, Prof Linkoeping University

Linkoeping University

Phone: +46 13 28 68 54

Email: Johnny.Ludvigsson@liu.se

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place