Trial Outcomes & Findings for A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 (NCT NCT04279613)

NCT ID: NCT04279613

Last Updated: 2025-05-20

Results Overview

Number of adverse events recorded during the on-treatment period, which is defined as from first treatment through visit 15 (or 5 weeks after last treatment for subjects not receiving all injections)

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 47 participants
• Primary outcome timeframe: 16 Weeks
• Results posted on: 2025-05-20

Participant Flow

Participant milestones

Measure	1 mg/0.11 mL NNC0361-0041 Plasmid Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 1: 1mg/0.11 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	5 mg/0.56 mL NNC0361-0041 Plasmid Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 2: 5mg/0.56 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	12.5 mg/1.4 mL NNC0361-0041 Plasmid Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 3: 12.5mg/ 1.4 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	25 mg/2.8 mL NNC0361-0041 Plasmid Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 4: 25mg/2.8 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	Placebo Dosage form: 0 mg/mL Isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 total injections, equivalent volume as prepared IMP Placebo: Placebo
Cohort 1: Dose Level 1 mg STARTED	9	0	0	0	3
Cohort 1: Dose Level 1 mg COMPLETED	9	0	0	0	2
Cohort 1: Dose Level 1 mg NOT COMPLETED	0	0	0	0	1
Cohort 2: Dose Level 5 mg STARTED	0	9	0	0	3
Cohort 2: Dose Level 5 mg COMPLETED	0	8	0	0	3
Cohort 2: Dose Level 5 mg NOT COMPLETED	0	1	0	0	0
Cohort 3: Dose Level 12.5 mg STARTED	0	0	9	0	3
Cohort 3: Dose Level 12.5 mg COMPLETED	0	0	8	0	3
Cohort 3: Dose Level 12.5 mg NOT COMPLETED	0	0	1	0	0
Cohort 4: Dose Level 25 mg STARTED	0	0	0	8	3
Cohort 4: Dose Level 25 mg COMPLETED	0	0	0	7	2
Cohort 4: Dose Level 25 mg NOT COMPLETED	0	0	0	1	1

Reasons for withdrawal

Measure	1 mg/0.11 mL NNC0361-0041 Plasmid Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 1: 1mg/0.11 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	5 mg/0.56 mL NNC0361-0041 Plasmid Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 2: 5mg/0.56 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	12.5 mg/1.4 mL NNC0361-0041 Plasmid Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 3: 12.5mg/ 1.4 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	25 mg/2.8 mL NNC0361-0041 Plasmid Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 4: 25mg/2.8 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	Placebo Dosage form: 0 mg/mL Isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 total injections, equivalent volume as prepared IMP Placebo: Placebo
Cohort 1: Dose Level 1 mg Protocol Violation	0	0	0	0	1
Cohort 2: Dose Level 5 mg Adverse Event	0	1	0	0	0
Cohort 3: Dose Level 12.5 mg Protocol Violation	0	0	1	0	0
Cohort 4: Dose Level 25 mg Adverse Event	0	0	0	0	1
Cohort 4: Dose Level 25 mg Withdrawal by Subject	0	0	0	1	0

Baseline Characteristics

A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041

Baseline characteristics by cohort

Measure	1 mg/0.11 mL NNC0361-0041 Plasmid n=9 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 1: 1mg/0.11 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	5 mg/0.56 mL NNC0361-0041 Plasmid n=9 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 2: 5mg/0.56 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	12.5 mg/1.4 mL NNC0361-0041 Plasmid n=9 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 3: 12.5mg/ 1.4 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	25 mg/2.8 mL NNC0361-0041 Plasmid n=8 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 4: 25mg/2.8 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	Placebo n=12 Participants Dosage form: 0 mg/mL Isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 total injections, equivalent volume as prepared IMP Placebo: Placebo	Total n=47 Participants Total of all reporting groups
Age, Continuous	36.7 years STANDARD_DEVIATION 7.62 • n=5 Participants	30.9 years STANDARD_DEVIATION 6 • n=7 Participants	25.3 years STANDARD_DEVIATION 4.57 • n=5 Participants	29.5 years STANDARD_DEVIATION 7.43 • n=4 Participants	29.1 years STANDARD_DEVIATION 7.85 • n=21 Participants	30.2 years STANDARD_DEVIATION 7.52 • n=8 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	25 Participants n=8 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	8 Participants n=21 Participants	22 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	9 Participants n=7 Participants	7 Participants n=5 Participants	8 Participants n=4 Participants	12 Participants n=21 Participants	45 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	8 Participants n=4 Participants	11 Participants n=21 Participants	42 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Diagnosis to Randomization	17.8 months STANDARD_DEVIATION 15.3 • n=5 Participants	20.2 months STANDARD_DEVIATION 12.8 • n=7 Participants	10.8 months STANDARD_DEVIATION 7.77 • n=5 Participants	19 months STANDARD_DEVIATION 14.1 • n=4 Participants	15.7 months STANDARD_DEVIATION 12.6 • n=21 Participants	16.6 months STANDARD_DEVIATION 12.6 • n=8 Participants
Weight	72.2 kg STANDARD_DEVIATION 14.4 • n=5 Participants	72 kg STANDARD_DEVIATION 11.5 • n=7 Participants	71.9 kg STANDARD_DEVIATION 11 • n=5 Participants	75.9 kg STANDARD_DEVIATION 13.3 • n=4 Participants	79.9 kg STANDARD_DEVIATION 17.3 • n=21 Participants	75.2 kg STANDARD_DEVIATION 13.5 • n=8 Participants
BMI	24.1 kg/m^2 STANDARD_DEVIATION 4.43 • n=5 Participants	25.6 kg/m^2 STANDARD_DEVIATION 3.36 • n=7 Participants	24.8 kg/m^2 STANDARD_DEVIATION 3.63 • n=5 Participants	26 kg/m^2 STANDARD_DEVIATION 4.24 • n=4 Participants	25.1 kg/m^2 STANDARD_DEVIATION 3.73 • n=21 Participants	25.1 kg/m^2 STANDARD_DEVIATION 3.76 • n=8 Participants
Autoantibodies positive GAD	9 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	7 Participants n=4 Participants	12 Participants n=21 Participants	45 Participants n=8 Participants
Autoantibodies positive IA-2	2 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants	10 Participants n=21 Participants	27 Participants n=8 Participants
Autoantibodies positive ICA	6 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants	24 Participants n=8 Participants
Autoantibodies positive Micro-IAA	5 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants	10 Participants n=21 Participants	36 Participants n=8 Participants
Autoantibodies positive ZnT8	5 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants	7 Participants n=21 Participants	27 Participants n=8 Participants
Count of autoantibodies positive 1	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	5 Participants n=8 Participants
Count of autoantibodies positive 2	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	7 Participants n=8 Participants
Count of autoantibodies positive 3	4 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	11 Participants n=8 Participants
Count of autoantibodies positive 4	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	13 Participants n=8 Participants
Count of autoantibodies positive 5	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	11 Participants n=8 Participants
Glycated hemoglobin level	6.08 % STANDARD_DEVIATION 0.565 • n=5 Participants	6.36 % STANDARD_DEVIATION 0.922 • n=7 Participants	6.01 % STANDARD_DEVIATION 0.692 • n=5 Participants	6.15 % STANDARD_DEVIATION 0.949 • n=4 Participants	6.36 % STANDARD_DEVIATION 0.817 • n=21 Participants	6.21 % STANDARD_DEVIATION 0.779 • n=8 Participants
C-peptide AUC Mean	0.838 pmol/mL STANDARD_DEVIATION 0.385 • n=5 Participants	0.645 pmol/mL STANDARD_DEVIATION 0.417 • n=7 Participants	0.943 pmol/mL STANDARD_DEVIATION 0.78 • n=5 Participants	0.691 pmol/mL STANDARD_DEVIATION 0.623 • n=4 Participants	0.753 pmol/mL STANDARD_DEVIATION 0.314 • n=21 Participants	0.774 pmol/mL STANDARD_DEVIATION 0.505 • n=8 Participants
Average total daily dose of Insulin	22.5 Units of Insulin STANDARD_DEVIATION 16.6 • n=5 Participants	31.3 Units of Insulin STANDARD_DEVIATION 22.5 • n=7 Participants	25.8 Units of Insulin STANDARD_DEVIATION 14.9 • n=5 Participants	26.4 Units of Insulin STANDARD_DEVIATION 12.3 • n=4 Participants	31.2 Units of Insulin STANDARD_DEVIATION 20.7 • n=21 Participants	27.9 Units of Insulin STANDARD_DEVIATION 17.9 • n=8 Participants

PRIMARY outcome

Timeframe: 16 Weeks

Population: The safety analysis set contained all participants who recieved at least one dose of study treatment.

Number of adverse events recorded during the on-treatment period, which is defined as from first treatment through visit 15 (or 5 weeks after last treatment for subjects not receiving all injections)

Outcome measures

Measure	1 mg/0.11 mL NNC0361-0041 Plasmid n=9 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 1: 1mg/0.11 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	5 mg/0.56 mL NNC0361-0041 Plasmid n=9 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 2: 5mg/0.56 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	12.5 mg/1.4 mL NNC0361-0041 Plasmid n=9 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 3: 12.5mg/ 1.4 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	25 mg/2.8 mL NNC0361-0041 Plasmid n=8 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 4: 25mg/2.8 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	Placebo n=12 Participants Dosage form: 0 mg/mL Isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 total injections, equivalent volume as prepared IMP Placebo: Placebo
Adverse Events	230 adverse events	217 adverse events	215 adverse events	169 adverse events	240 adverse events

SECONDARY outcome

Timeframe: 4-, 12-, 24- and 52-weeks from baseline

Population: number of participants analyzed differs in one or more of the rows due to a participant not completing the assessment (MMTT) required to include in computing the geometric mean of the C-peptide change from baseline.

Proportional change from baseline c-peptide AUC mean from a 2-hour mixed meal tolerance test by assessment schedule. The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis.

Outcome measures

Measure	1 mg/0.11 mL NNC0361-0041 Plasmid n=9 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 1: 1mg/0.11 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	5 mg/0.56 mL NNC0361-0041 Plasmid n=8 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 2: 5mg/0.56 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	12.5 mg/1.4 mL NNC0361-0041 Plasmid n=7 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 3: 12.5mg/ 1.4 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	25 mg/2.8 mL NNC0361-0041 Plasmid n=7 Participants Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 4: 25mg/2.8 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	Placebo n=10 Participants Dosage form: 0 mg/mL Isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 total injections, equivalent volume as prepared IMP Placebo: Placebo
Change in the Area Under the Plasma C-peptide Concentration-time Curve Across the 2-hour Test Period. 4 weeks	0.861 pmol/mL Interval 0.741 to 1.0	0.955 pmol/mL Interval 0.729 to 1.25	1.15 pmol/mL Interval 0.845 to 1.55	0.823 pmol/mL Interval 0.645 to 1.05	0.8 pmol/mL Interval 0.695 to 0.921
Change in the Area Under the Plasma C-peptide Concentration-time Curve Across the 2-hour Test Period. 12 weeks	0.83 pmol/mL Interval 0.724 to 0.95	0.807 pmol/mL Interval 0.608 to 1.07	0.914 pmol/mL Interval 0.602 to 1.39	0.775 pmol/mL Interval 0.646 to 0.931	0.794 pmol/mL Interval 0.681 to 0.927
Change in the Area Under the Plasma C-peptide Concentration-time Curve Across the 2-hour Test Period. 24 weeks	0.761 pmol/mL Interval 0.611 to 0.946	0.655 pmol/mL Interval 0.411 to 1.05	0.93 pmol/mL Interval 0.704 to 1.23	0.809 pmol/mL Interval 0.638 to 1.03	0.764 pmol/mL Interval 0.63 to 1.0
Change in the Area Under the Plasma C-peptide Concentration-time Curve Across the 2-hour Test Period. 52 weeks	0.742 pmol/mL Interval 0.549 to 1.0	0.626 pmol/mL Interval 0.467 to 0.841	1.01 pmol/mL Interval 0.705 to 1.46	0.65 pmol/mL Interval 0.467 to 0.905	0.585 pmol/mL Interval 0.495 to 0.692

Adverse Events

1 mg/0.11 mL NNC0361-0041 Plasmid

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

5 mg/0.56 mL NNC0361-0041 Plasmid

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

12.5 mg/1.4 mL NNC0361-0041 Plasmid

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

25 mg/2.8 mL NNC0361-0041 Plasmid

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	1 mg/0.11 mL NNC0361-0041 Plasmid n=9 participants at risk Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 1: 1mg/0.11 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	5 mg/0.56 mL NNC0361-0041 Plasmid n=9 participants at risk Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 2: 5mg/0.56 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	12.5 mg/1.4 mL NNC0361-0041 Plasmid n=9 participants at risk Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 3: 12.5mg/ 1.4 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	25 mg/2.8 mL NNC0361-0041 Plasmid n=8 participants at risk Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 4: 25mg/2.8 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	Placebo n=12 participants at risk Dosage form: 0 mg/mL Isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 total injections, equivalent volume as prepared IMP Placebo: Placebo
Endocrine disorders Adrenal insufficiency	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/8 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/12 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Nervous system disorders Dizziness	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/8 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/12 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.

Other adverse events

Measure	1 mg/0.11 mL NNC0361-0041 Plasmid n=9 participants at risk Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 1: 1mg/0.11 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	5 mg/0.56 mL NNC0361-0041 Plasmid n=9 participants at risk Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 2: 5mg/0.56 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	12.5 mg/1.4 mL NNC0361-0041 Plasmid n=9 participants at risk Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 3: 12.5mg/ 1.4 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	25 mg/2.8 mL NNC0361-0041 Plasmid n=8 participants at risk Dosage form: 9 mg/ml plasmid in isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 injections Dose/Unit strength in cohort 4: 25mg/2.8 mL NNC0361-0041: Recombinant supercoiled plasmid encoding four human proteins: (pre-proinsulin (PPI), transforming growth factor β1 (TGF-β1), interleukin-10 (IL-10), and interleukin-2 (IL-2).	Placebo n=12 participants at risk Dosage form: 0 mg/mL Isotonic solution for injection Route of administration: Subcutaneous injection (into the abdomen) Dosing instructions: Once weekly on site for 12 total injections, equivalent volume as prepared IMP Placebo: Placebo
Investigations Investigations	100.0% 9/9 • Number of events 96 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	100.0% 9/9 • Number of events 143 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	100.0% 9/9 • Number of events 133 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	100.0% 8/8 • Number of events 81 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	100.0% 12/12 • Number of events 134 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Vascular disorders Vascular disorders	88.9% 8/9 • Number of events 46 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	88.9% 8/9 • Number of events 33 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	66.7% 6/9 • Number of events 21 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	87.5% 7/8 • Number of events 21 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	83.3% 10/12 • Number of events 36 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
General disorders General disorders and administration site conditions	66.7% 6/9 • Number of events 23 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	22.2% 2/9 • Number of events 9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	44.4% 4/9 • Number of events 10 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	62.5% 5/8 • Number of events 16 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	58.3% 7/12 • Number of events 19 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Metabolism and nutrition disorders Metabolism and nutrition disorders	66.7% 6/9 • Number of events 15 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	44.4% 4/9 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	33.3% 3/9 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	50.0% 4/8 • Number of events 7 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	50.0% 6/12 • Number of events 14 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Infections and infestations Infections and infestations	55.6% 5/9 • Number of events 7 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	55.6% 5/9 • Number of events 6 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	55.6% 5/9 • Number of events 9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	37.5% 3/8 • Number of events 4 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	25.0% 3/12 • Number of events 3 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Blood and lymphatic system disorders Blood and lymphatic system disorders	22.2% 2/9 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	77.8% 7/9 • Number of events 16 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	66.7% 6/9 • Number of events 10 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	50.0% 4/8 • Number of events 6 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	16.7% 2/12 • Number of events 7 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Gastrointestinal disorders Gastrointestinal disorders	55.6% 5/9 • Number of events 10 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	44.4% 4/9 • Number of events 7 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	33.3% 3/9 • Number of events 9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	37.5% 3/8 • Number of events 8 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	33.3% 4/12 • Number of events 4 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Nervous system disorders Nervous system disorders	44.4% 4/9 • Number of events 18 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	33.3% 3/9 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	33.3% 3/9 • Number of events 10 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	50.0% 4/8 • Number of events 13 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	25.0% 3/12 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	55.6% 5/9 • Number of events 13 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	44.4% 4/9 • Number of events 6 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	25.0% 2/8 • Number of events 3 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	33.3% 4/12 • Number of events 7 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	22.2% 2/9 • Number of events 7 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	22.2% 2/9 • Number of events 3 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	37.5% 3/8 • Number of events 4 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	41.7% 5/12 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Renal and urinary disorders Renal and urinary disorders	66.7% 6/9 • Number of events 8 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	44.4% 4/9 • Number of events 6 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	12.5% 1/8 • Number of events 3 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	8.3% 1/12 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	33.3% 3/9 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	37.5% 3/8 • Number of events 9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	33.3% 4/12 • Number of events 7 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	33.3% 3/9 • Number of events 7 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	22.2% 2/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	12.5% 1/8 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	25.0% 3/12 • Number of events 4 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Cardiac disorders Cardiac disorders	22.2% 2/9 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	22.2% 2/9 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/8 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	25.0% 3/12 • Number of events 5 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Psychiatric disorders Psychiatric disorders	11.1% 1/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	22.2% 2/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	25.0% 2/8 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	16.7% 2/12 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Eye disorders Eye disorders	22.2% 2/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/8 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	16.7% 2/12 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Endocrine disorders Endocrine disorders	22.2% 2/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	12.5% 1/8 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/12 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Immune system disorders Immune system disorders	22.2% 2/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	12.5% 1/8 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	8.3% 1/12 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Ear and labyrinth disorders Ear and labyrinth disorders	22.2% 2/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/8 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	8.3% 1/12 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.
Reproductive system and breast disorders Reproductive system and breast disorders	11.1% 1/9 • Number of events 2 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	11.1% 1/9 • Number of events 1 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/9 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/8 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.	0.00% 0/12 • Baseline visit (V0) through week 52 study visit (V17) From study start through visit 15, all adverse events which were grade 1 or greater per the NCI CTCAE v5.0 were required to be reported. For visits 16 and 17 only grade 2 or greater were to be reported. Hypoglycemia/hyperglycemia only to be reported as AEs in the case of requiring assistance of others due to loss of consciousness/DKA. All SAEs were required to be reported. Adverse events were analyzed based on organ class system without regard to the specific adverse event term.

Additional Information

Dr. Kevan Herold

Yale University

Phone: 203-785-6507

Email: kevan.herold@yale.edu

Results disclosure agreements

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