Trial Outcomes & Findings for Diamyd Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes (NCT NCT03345004)

NCT ID: NCT03345004

Last Updated: 2023-01-09

Results Overview

Change in C-peptide between Baseline and 15 Months. C-peptide was measured by Area Under the Curve \[AUC\] at 0-120 min during a Mixed Meal Tolerance Test (MMTT) and divided by 120 min. The results are given as the ratio (back-transformed from log-scale) between 15 Months and Baseline as predicted by the MMRM (Mixed Model Repeated Measures) model.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 109 participants
• Primary outcome timeframe: Baseline and 15 months
• Results posted on: 2023-01-09

Participant Flow

Participant milestones

Measure	Active Arm Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg recombinant human Glutamic Acid Decarboxylase adsorbed to Alhydrogel (Diamyd) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Overall Study STARTED	57	52
Overall Study Haplotype DR3-DQ2 Population Month 15	29	19
Overall Study COMPLETED	56	51
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Active Arm Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg recombinant human Glutamic Acid Decarboxylase adsorbed to Alhydrogel (Diamyd) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Active Arm n=57 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120) GAD-alum: Alhydrogel®-formulated recombinant human glutamic acid decarboxylase (rhGAD) Vitamin D: Oil suspension of Vitamin D	Placebo Arm n=52 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120) Placebo for Diamyd (GAD-alum): Alhydrogel® only Placebo for Vitamin D: Placebo oil suspension for Vitamin D	Total n=109 Participants Total of all reporting groups
Age, Continuous	16.2 years STANDARD_DEVIATION 3.8 • n=57 Participants	16.6 years STANDARD_DEVIATION 4.3 • n=52 Participants	16.4 years STANDARD_DEVIATION 4.1 • n=109 Participants
Sex: Female, Male Female	21 Participants n=57 Participants	26 Participants n=52 Participants	47 Participants n=109 Participants
Sex: Female, Male Male	36 Participants n=57 Participants	26 Participants n=52 Participants	62 Participants n=109 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: Baseline and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. 1 patient in the active arm and 4 patients in the placebo arm were excluded due to lack of primary efficacy data at Visit 7.

Change in C-peptide between Baseline and 15 Months. C-peptide was measured by Area Under the Curve [AUC] at 0-120 min during a Mixed Meal Tolerance Test (MMTT) and divided by 120 min. The results are given as the ratio (back-transformed from log-scale) between 15 Months and Baseline as predicted by the MMRM (Mixed Model Repeated Measures) model.

Outcome measures

Measure	Active Arm n=55 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=48 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=29 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=17 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in Stimulated C-peptide During a MMTT	0.551 Unitless back-transformed from log-scale Standard Deviation 1.715	0.506 Unitless back-transformed from log-scale Standard Deviation 2.163	0.663 Unitless back-transformed from log-scale Standard Deviation 1.511	0.425 Unitless back-transformed from log-scale Standard Deviation 2.436

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

Change in insulin-dose-adjusted HbA1c (IDAA1c)

Outcome measures

Measure	Active Arm n=51 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=44 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=28 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=15 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in IDAA1c	0.757 Percent of glycated hemoglobin Standard Deviation 1.851	0.377 Percent of glycated hemoglobin Standard Deviation 2.183	0.663 Percent of glycated hemoglobin Standard Deviation 1.627	0.667 Percent of glycated hemoglobin Standard Deviation 2.788

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable.

Change in HbA1c (mmol/mol)

Outcome measures

Measure	Active Arm n=56 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=51 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=29 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=18 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in HbA1c	0.53 mmol/mol Standard Deviation 14.57	1.04 mmol/mol Standard Deviation 15.87	0.87 mmol/mol Standard Deviation 14.34	-0.98 mmol/mol Standard Deviation 18.75

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

Change in daily exogenous insulin consumption (IU)

Outcome measures

Measure	Active Arm n=51 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=44 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=28 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=15 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in Insulin Consumption	0.183 IU/kg/24h Standard Deviation 0.285	0.094 IU/kg/24h Standard Deviation 0.342	0.143 IU/kg/24h Standard Deviation 0.196	0.153 IU/kg/24h Standard Deviation 0.399

SECONDARY outcome

Timeframe: Screening and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

Change in glycemic variability/fluctuations (evaluated from data from continuous glucose monitoring FreeStyle LibrePro, FGM) over 14 day period.

Outcome measures

Measure	Active Arm n=49 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=39 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=25 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=12 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in Glycemic Variability/Fluctuations 70-180 mg/dL (hours)	-2.479 glycemic variability/fluctuation per day Standard Deviation 4.638	-2.451 glycemic variability/fluctuation per day Standard Deviation 4.012	-1.724 glycemic variability/fluctuation per day Standard Deviation 3.346	-3.920 glycemic variability/fluctuation per day Standard Deviation 4.090
Change in Glycemic Variability/Fluctuations 50-70 mg/dL (hours)	-0.035 glycemic variability/fluctuation per day Standard Deviation 2.416	0.197 glycemic variability/fluctuation per day Standard Deviation 1.961	0.034 glycemic variability/fluctuation per day Standard Deviation 2.992	0.581 glycemic variability/fluctuation per day Standard Deviation 1.057
Change in Glycemic Variability/Fluctuations <50 mg/dL (minutes)	15.7 glycemic variability/fluctuation per day Standard Deviation 46.7	9.0 glycemic variability/fluctuation per day Standard Deviation 88.4	16.7 glycemic variability/fluctuation per day Standard Deviation 59.3	48.1 glycemic variability/fluctuation per day Standard Deviation 107.0

SECONDARY outcome

Timeframe: 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

Percentage of patients with IDAA1c ≤ 9

Outcome measures

Measure	Active Arm n=51 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=44 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=28 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=15 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Percentage of Patients With IDAA1c ≤ 9	62.7 Percent of patients Interval 48.1 to 75.9	61.4 Percent of patients Interval 45.5 to 75.6	78.6 Percent of patients Interval 59.0 to 91.7	40.0 Percent of patients Interval 16.3 to 67.7

SECONDARY outcome

Timeframe: 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

Percentage of patients with a stimulated maximum C-peptide level above 0.2 nmol/L (0.6 ng/ml)

Outcome measures

Measure	Active Arm n=55 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=49 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=29 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=17 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Stimulated Maximum C-peptide Above 0.2 Nmol/L	92.7 Percent of patients Interval 82.4 to 98.0	75.7 Percent of patients Interval 61.1 to 86.7	96.6 Percent of patients Interval 82.2 to 99.9	70.6 Percent of patients Interval 44.0 to 89.7

SECONDARY outcome

Timeframe: 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

Percentage of patients with a stimulated 90min C-peptide level above 0.2 nmol/L (0.6 ng/ml)

Outcome measures

Measure	Active Arm n=55 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=49 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=29 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=17 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Stimulated C-peptide Above 0.2 Nmol/L at 90 Min	87.3 Percent of patients Interval 75.5 to 94.7	71.4 Percent of patients Interval 56.7 to 83.4	96.6 Percent of patients Interval 82.2 to 99.9	64.7 Percent of patients Interval 38.3 to 85.8

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.

Number of self-reported episodes of severe hypoglycemia (Severe hypoglycemia defined as needing help from others and/or seizures and/or unconscious) (counts)

Outcome measures

Measure	Active Arm n=57 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=52 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=29 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=19 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Number of Hypoglycemias	0 Episodes	6 Episodes	0 Episodes	0 Episodes

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.

Number of patients having at least 1 severe hypoglycemic event (counts)

Outcome measures

Measure	Active Arm n=57 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=52 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=29 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=19 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Number of Patients Having at Least 1 Severe Hypoglycemic Event	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

Change in maximum C-peptide during MMTT (nmol/L)

Outcome measures

Measure	Active Arm n=55 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=49 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=29 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=17 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in Maximum C-peptide	-0.350 nmol/L Standard Deviation 0.463	-0.300 nmol/L Standard Deviation 0.350	-0.257 nmol/L Standard Deviation 0.400	-0.277 nmol/L Standard Deviation 0.349

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

Change in Fasting C-peptide (nmol/L)

Outcome measures

Measure	Active Arm n=55 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=49 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=29 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=17 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in Fasting C-peptide	-0.115 nmol/L Standard Deviation 0.148	-0.106 nmol/L Standard Deviation 0.169	-0.081 nmol/L Standard Deviation 0.100	-0.095 nmol/L Standard Deviation 0.190

SECONDARY outcome

Timeframe: 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

C-peptide measured at 30, 60, 90, and 120 minutes during MMTT (nmol/L) at 15 months

Outcome measures

Measure	Active Arm n=55 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=49 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) n=29 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) n=19 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
C-peptide Levels During a MMTT 30 min	0.376 nmol/L Standard Deviation 0.295	0.374 nmol/L Standard Deviation 0.330	0.659 nmol/L Standard Deviation 0.352	0.580 nmol/L Standard Deviation 0.282
C-peptide Levels During a MMTT 60 min	0.536 nmol/L Standard Deviation 0.383	0.495 nmol/L Standard Deviation 0.411	0.911 nmol/L Standard Deviation 0.393	0.715 nmol/L Standard Deviation 0.308
C-peptide Levels During a MMTT 90 min	0.645 nmol/L Standard Deviation 0.495	0.562 nmol/L Standard Deviation 0.438	1.016 nmol/L Standard Deviation 0.415	0.717 nmol/L Standard Deviation 0.318
C-peptide Levels During a MMTT 120 min	0.691 nmol/L Standard Deviation 0.542	0.590 nmol/L Standard Deviation 0.444	1.065 nmol/L Standard Deviation 0.430	0.728 nmol/L Standard Deviation 0.317

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable.

Change in body weight (kg)

Outcome measures

Measure	Active Arm n=56 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=51 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in Body Weight	4.3 Kg Standard Deviation 5.0	5.6 Kg Standard Deviation 5.4	—	—

SECONDARY outcome

Timeframe: 15 months

Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.

Injection site reactions

Outcome measures

Measure	Active Arm n=57 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=52 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Injection Site Reactions	10 number of episodes	3 number of episodes	—	—

SECONDARY outcome

Timeframe: 15 months

Population: Safety Analysis Set, consist of all randomized patients who received at least one injection.

Number of clinically significant abnormal results from laboratory measurements (haematology and clinical chemistry) and urinalysis. (counts)

Outcome measures

Measure	Active Arm n=57 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=52 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Number of Clinically Significant Abnormal Results From Laboratory Measurements (Haematology and Clinical Chemistry) and Urinalysis.	11 number of significant abnormal results	3 number of significant abnormal results	—	—

SECONDARY outcome

Timeframe: 15 months

Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.

Physical examination (general appearance including skin, mouth, throat, cardiovascular, abdomen, lymphatic glands, and neurological/musculoskeletal [including reflexes]).

Standardised clinical neurological examination including extremity reflexes, Romberg, Walk on a line, 2 meters, Standing on 1 leg, left and right, 15 seconds per leg, Finger-nose, Mimic, Babinski reflex.

The outcome of the assessments was recored as "normal" or "abnormal"

Outcome measures

Measure	Active Arm n=57 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=52 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations Physical examination	15 Clinically significant abnormal results	9 Clinically significant abnormal results	—	—
Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations Neurological examination	4 Clinically significant abnormal results	0 Clinically significant abnormal results	—	—

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.

GAD65A titer (IU/ml)

Outcome measures

Measure	Active Arm n=57 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=52 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
GAD65A Titer Baseline	731.3 IU/mL Standard Deviation 2302.9	627.3 IU/mL Standard Deviation 1829.9	—	—
GAD65A Titer Month 15	19941.2 IU/mL Standard Deviation 23083.6	476.7 IU/mL Standard Deviation 1527.7	—	—

SECONDARY outcome

Timeframe: 15 months

Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.

Vital signs (blood pressure) (mmHg)

Outcome measures

Measure	Active Arm n=57 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=52 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Number of Clinically Significant Abnormal Results in Vital Signs Systolic blood pressure	0 Clinically significant abnormal results	0 Clinically significant abnormal results	—	—
Number of Clinically Significant Abnormal Results in Vital Signs Diastolic blood pressure	0 Clinically significant abnormal results	0 Clinically significant abnormal results	—	—

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable. Patients with missing data are excluded.

Change in QoL as measured by the standardised measure of health questionnaire EQ-5D-5L between baseline and Month 15. The EQ-5D-5L is based on 5 questions rated at 5 levels indicating from no problem (level 1) to extreme problems (level 5) regarding current state of mobility, self-care, activity, pain and anxiety. The outcome is presented as a weighted index value, where 1 is the best possible health and 0 represents being dead.

Outcome measures

Measure	Active Arm n=48 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=47 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in Quality of Life (QoL) Baseline	1.000 Index value Interval 0.922 to 1.0	1.000 Index value Interval 0.919 to 1.0	—	—
Change in Quality of Life (QoL) Month 15	1.000 Index value Interval 0.919 to 1.0	1.000 Index value Interval 1.0 to 1.0	—	—

SECONDARY outcome

Timeframe: Baseline and 15 months

Population: Full analysis set, consist of all randomized patients who have received at least one dose of study medication and have at least one postbaseline assessment and corresponding baseline measurement of any efficacy variable.

Change in BMI (kg/m2)

Outcome measures

Measure	Active Arm n=56 Participants Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=51 Participants Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)	Active (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo (HLA DR3-DQ2) Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Change in Body Mass Index (BMI)	0.8 kg/m2 Standard Deviation 1.4	1.3 kg/m2 Standard Deviation 1.6	—	—

Adverse Events

Active Arm

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Active Arm n=57 participants at risk Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=52 participants at risk Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Injury, poisoning and procedural complications Jaw fracture	0.00% 0/57 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.	1.9% 1/52 • Number of events 1 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.
Metabolism and nutrition disorders Diabetes Mellitus inadequate control	0.00% 0/57 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.	1.9% 1/52 • Number of events 1 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/57 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.	1.9% 1/52 • Number of events 1 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.

Other adverse events

Measure	Active Arm n=57 participants at risk Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)	Placebo Arm n=52 participants at risk Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 3/57 • Number of events 4 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.	3.8% 2/52 • Number of events 2 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.
General disorders Pyrexia	5.3% 3/57 • Number of events 3 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.	5.8% 3/52 • Number of events 3 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.
Infections and infestations Nasopharyngitis	17.5% 10/57 • Number of events 13 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.	19.2% 10/52 • Number of events 17 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.
Infections and infestations Viral infection	7.0% 4/57 • Number of events 4 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.	0.00% 0/52 • Treatment-emergent adverse events, from start of Diamyd/Placebo treatment until Month 24.

Additional Information

Director of Clinical Development

Diamyd Medical AB

Phone: +46 (0) 8 661 00 26

Email: clinicaltrials@diamyd.com

Results disclosure agreements

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

Restriction type: LTE60