Autoimmune Diabetes, Autoimmune Diseases, Diabetes Mellitus, Diabetes Mellitus, Type 1, Endocrine System Diseases, Glucose Metabolism Disorders, Immune System Diseases, Insulin Dependent Diabetes, Juvenile Diabetes, Metabolic Disease, Physiological Effects of Drugs, Vitamin D
Conditions
Keywords
Diamyd, Diabetes, Juvenile Diabetes, Diabetes Type 1, Type 1 Diabetes, Autoimmune Diabetes, Insulin Dependent Diabetes, Type 1 Diabetes Mellitus, rhGAD65, GAD65, Diabetes Mellitus, Diabetes Mellitus Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Vitamin D, Vitamins, Micronutrients, Cholecalciferol, Ergocalciferols
Brief summary
The objective of DIAGNODE-2 is to evaluate the efficacy of Diamyd compared to Placebo, upon administration directly into a lymph node in combination with an oral vitamin D/Placebo regimen, in terms of preserving endogenous insulin secretion as measured by C-peptide.
Detailed description
The study is a 2-arm, randomized, double-blind, placebo-controlled, multicenter, clinical trial. Eligible patients will receive injections of Diamyd/placebo into an inguinal lymph gland at three occasions, with one month intervals in combination with an oral vitamin D/placebo regimen (starting 1 month ahead of injections) during 4 months. All patients will continue to receive intensive insulin treatment from their personal physicians during the whole study period. The patients will be followed in a blinded manner for a total of 15 months. All patients that have not performed the 15 months visit when the updated protocol is implemented, will be asked to participate in the Extension Study Period which includes an additional visit at month 24.
Interventions
BIOLOGICALDiamyd
Alhydrogel®-formulated recombinant human glutamic acid decarboxylase (rhGAD65)
DIETARY_SUPPLEMENTVitamin D
Oil suspension of Vitamin D
BIOLOGICALPlacebo for Diamyd
Alhydrogel® only
DIETARY_SUPPLEMENTPlacebo for Vitamin D
Placebo oil suspension for Vitamin D
Sponsors
Diamyd Medical AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
The study is a 2-arm, randomized, double-blind, placebo-controlled, multicenter, clinical trial.
Eligibility
Sex/Gender
ALL
Age
12 Years to 24 Years
Healthy volunteers
No
Inclusion criteria
1. Informed consent given by patients and/or patient's parent(s) or legal acceptable representative(s) (guardian(s)) according to national regulations 2. Type 1 Diabetes (T1D) according to the Amercian Diabetes Association (ADA) classification diagnosed ≤6 months at the time of screening 3. Age: ≥12 and \<25 years old 4. Fasting C-peptide ≥0.12 nmol/L (0.36 ng/ml) on at least one occasion (maximum 2 tests on different days within a period of 2 weeks) 5. Positive for Glutamic Acid Decarboxylase isoform 65 (GAD65A) but \< 50 000 IU/ml 6. Females must agree to avoid pregnancy and have a negative urine pregnancy test. Patients of childbearing potential must agree to use adequate contraception, until one (1) year after the last administration of Diamyd. Adequate contraception is as follows: For females of childbearing potential: 1. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives 2. combined (estrogen and progestogen containing) 3. oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation 4. intrauterine device 5. intrauterine hormone-releasing system (for example, progestin-releasing coil) 6. bilateral tubal occlusion 7. vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate) 8. male partner using condom 9. abstinence from heterosexual intercourse For males of childbearing potential: 1. condom (male) 2. abstinence from heterosexual intercourse
Exclusion criteria
1. Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted) 2. Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted) 3. Treatment with any oral or injected anti-diabetic medications other than insulin 4. A history of anemia or significantly abnormal hematology results at screening 5. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles 6. Clinically significant history of acute reaction to vaccines or other drugs in the past 7. Treatment with any vaccine, including influenza vaccine, within 4 months prior to planned first study drug dose or planned treatment with any vaccine up to 4 months after the last injection with study drug. 8. Participation in other clinical trials with a new chemical entity within the previous 3 months 9. Inability or unwillingness to comply with the provisions of this protocol 10. A history of alcohol or drug abuse 11. A significant illness other than diabetes within 2 weeks prior to first dosing 12. Known HIV or hepatitis 13. Females who are lactating or pregnant (the possibility of pregnancy must be excluded by urine βHCG on-site within 24 hours prior to the Diamyd/placebo treatment) 14. Presence of associated serious disease or condition, including active skin infections that preclude intralymphatic injection, which in the opinion of the investigator makes the patient non-eligible for the study 15. Deemed by the investigator not being able to follow instructions and/or follow the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Stimulated C-peptide During a MMTT | Baseline and 15 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c | Baseline and 15 months | Change in HbA1c (mmol/mol) |
| Change in Insulin Consumption | Baseline and 15 months | Change in daily exogenous insulin consumption (IU) |
| Change in Glycemic Variability/Fluctuations | Screening and 15 months | Change in glycemic variability/fluctuations (evaluated from data from continuous glucose monitoring FreeStyle LibrePro, FGM) over 14 day period. |
| Percentage of Patients With IDAA1c ≤ 9 | 15 months | Percentage of patients with IDAA1c ≤ 9 |
| Stimulated Maximum C-peptide Above 0.2 Nmol/L | 15 months | Percentage of patients with a stimulated maximum C-peptide level above 0.2 nmol/L (0.6 ng/ml) |
| Stimulated C-peptide Above 0.2 Nmol/L at 90 Min | 15 months | Percentage of patients with a stimulated 90min C-peptide level above 0.2 nmol/L (0.6 ng/ml) |
| Number of Hypoglycemias | Baseline and 15 months | Number of self-reported episodes of severe hypoglycemia (Severe hypoglycemia defined as needing help from others and/or seizures and/or unconscious) (counts) |
| Number of Patients Having at Least 1 Severe Hypoglycemic Event | Baseline and 15 months | Number of patients having at least 1 severe hypoglycemic event (counts) |
| Change in Maximum C-peptide | Baseline and 15 months | Change in maximum C-peptide during MMTT (nmol/L) |
| Change in IDAA1c | Baseline and 15 months | Change in insulin-dose-adjusted HbA1c (IDAA1c) |
| C-peptide Levels During a MMTT | 15 months | C-peptide measured at 30, 60, 90, and 120 minutes during MMTT (nmol/L) at 15 months |
| Change in Body Weight | Baseline and 15 months | Change in body weight (kg) |
| Injection Site Reactions | 15 months | Injection site reactions |
| Number of Clinically Significant Abnormal Results From Laboratory Measurements (Haematology and Clinical Chemistry) and Urinalysis. | 15 months | Number of clinically significant abnormal results from laboratory measurements (haematology and clinical chemistry) and urinalysis. (counts) |
| Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations | 15 months | 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 |
| GAD65A Titer | Baseline and 15 months | GAD65A titer (IU/ml) |
| Number of Clinically Significant Abnormal Results in Vital Signs | 15 months | Vital signs (blood pressure) (mmHg) |
| Change in Quality of Life (QoL) | Baseline and 15 months | 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. |
| Change in Body Mass Index (BMI) | Baseline and 15 months | Change in BMI (kg/m2) |
| Change in Fasting C-peptide | Baseline and 15 months | Change in Fasting C-peptide (nmol/L) |
Countries
Czechia, Netherlands, Spain, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Arm 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 | 57 |
| Placebo Arm 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 | 52 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Active Arm | Placebo Arm | Total |
|---|---|---|---|
| Age, Continuous | 16.2 years STANDARD_DEVIATION 3.8 | 16.6 years STANDARD_DEVIATION 4.3 | 16.4 years STANDARD_DEVIATION 4.1 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 21 Participants | 26 Participants | 47 Participants |
| Sex: Female, Male Male | 36 Participants | 26 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 52 |
| other Total, other adverse events | 18 / 57 | 12 / 52 |
| serious Total, serious adverse events | 0 / 57 | 3 / 52 |
Outcome results
Primary
Change in Stimulated C-peptide During a MMTT
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Arm | Change in Stimulated C-peptide During a MMTT | 0.551 Unitless back-transformed from log-scale | Standard Deviation 1.715 |
| Placebo Arm | Change in Stimulated C-peptide During a MMTT | 0.506 Unitless back-transformed from log-scale | Standard Deviation 2.163 |
| Active (HLA DR3-DQ2) | Change in Stimulated C-peptide During a MMTT | 0.663 Unitless back-transformed from log-scale | Standard Deviation 1.511 |
| Placebo (HLA DR3-DQ2) | Change in Stimulated C-peptide During a MMTT | 0.425 Unitless back-transformed from log-scale | Standard Deviation 2.436 |
p-value: =0.500995% CI: [0.845, 1.408]Mixed Models Analysis
p-value: =0.007895% CI: [1.126, 2.153]Mixed Models Analysis
Secondary
Change in Body Mass Index (BMI)
Change in BMI (kg/m2)
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Arm | Change in Body Mass Index (BMI) | 0.8 kg/m2 | Standard Deviation 1.4 |
| Placebo Arm | Change in Body Mass Index (BMI) | 1.3 kg/m2 | Standard Deviation 1.6 |
Secondary
Change in Body Weight
Change in body weight (kg)
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Arm | Change in Body Weight | 4.3 Kg | Standard Deviation 5 |
| Placebo Arm | Change in Body Weight | 5.6 Kg | Standard Deviation 5.4 |
Secondary
Change in Fasting C-peptide
Change in Fasting C-peptide (nmol/L)
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Arm | Change in Fasting C-peptide | -0.115 nmol/L | Standard Deviation 0.148 |
| Placebo Arm | Change in Fasting C-peptide | -0.106 nmol/L | Standard Deviation 0.169 |
| Active (HLA DR3-DQ2) | Change in Fasting C-peptide | -0.081 nmol/L | Standard Deviation 0.1 |
| Placebo (HLA DR3-DQ2) | Change in Fasting C-peptide | -0.095 nmol/L | Standard Deviation 0.19 |
Secondary
Change in Glycemic Variability/Fluctuations
Change in glycemic variability/fluctuations (evaluated from data from continuous glucose monitoring FreeStyle LibrePro, FGM) over 14 day period.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Arm | Change in Glycemic Variability/Fluctuations | 70-180 mg/dL (hours) | -2.479 glycemic variability/fluctuation per day | Standard Deviation 4.638 |
| Active Arm | Change in Glycemic Variability/Fluctuations | 50-70 mg/dL (hours) | -0.035 glycemic variability/fluctuation per day | Standard Deviation 2.416 |
| Active Arm | Change in Glycemic Variability/Fluctuations | <50 mg/dL (minutes) | 15.7 glycemic variability/fluctuation per day | Standard Deviation 46.7 |
| Placebo Arm | Change in Glycemic Variability/Fluctuations | 50-70 mg/dL (hours) | 0.197 glycemic variability/fluctuation per day | Standard Deviation 1.961 |
| Placebo Arm | Change in Glycemic Variability/Fluctuations | <50 mg/dL (minutes) | 9.0 glycemic variability/fluctuation per day | Standard Deviation 88.4 |
| Placebo Arm | Change in Glycemic Variability/Fluctuations | 70-180 mg/dL (hours) | -2.451 glycemic variability/fluctuation per day | Standard Deviation 4.012 |
| Active (HLA DR3-DQ2) | Change in Glycemic Variability/Fluctuations | 70-180 mg/dL (hours) | -1.724 glycemic variability/fluctuation per day | Standard Deviation 3.346 |
| Active (HLA DR3-DQ2) | Change in Glycemic Variability/Fluctuations | <50 mg/dL (minutes) | 16.7 glycemic variability/fluctuation per day | Standard Deviation 59.3 |
| Active (HLA DR3-DQ2) | Change in Glycemic Variability/Fluctuations | 50-70 mg/dL (hours) | 0.034 glycemic variability/fluctuation per day | Standard Deviation 2.992 |
| Placebo (HLA DR3-DQ2) | Change in Glycemic Variability/Fluctuations | <50 mg/dL (minutes) | 48.1 glycemic variability/fluctuation per day | Standard Deviation 107 |
| Placebo (HLA DR3-DQ2) | Change in Glycemic Variability/Fluctuations | 70-180 mg/dL (hours) | -3.920 glycemic variability/fluctuation per day | Standard Deviation 4.09 |
| Placebo (HLA DR3-DQ2) | Change in Glycemic Variability/Fluctuations | 50-70 mg/dL (hours) | 0.581 glycemic variability/fluctuation per day | Standard Deviation 1.057 |
Secondary
Change in HbA1c
Change in HbA1c (mmol/mol)
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Arm | Change in HbA1c | 0.53 mmol/mol | Standard Deviation 14.57 |
| Placebo Arm | Change in HbA1c | 1.04 mmol/mol | Standard Deviation 15.87 |
| Active (HLA DR3-DQ2) | Change in HbA1c | 0.87 mmol/mol | Standard Deviation 14.34 |
| Placebo (HLA DR3-DQ2) | Change in HbA1c | -0.98 mmol/mol | Standard Deviation 18.75 |
Secondary
Change in IDAA1c
Change in insulin-dose-adjusted HbA1c (IDAA1c)
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Arm | Change in IDAA1c | 0.757 Percent of glycated hemoglobin | Standard Deviation 1.851 |
| Placebo Arm | Change in IDAA1c | 0.377 Percent of glycated hemoglobin | Standard Deviation 2.183 |
| Active (HLA DR3-DQ2) | Change in IDAA1c | 0.663 Percent of glycated hemoglobin | Standard Deviation 1.627 |
| Placebo (HLA DR3-DQ2) | Change in IDAA1c | 0.667 Percent of glycated hemoglobin | Standard Deviation 2.788 |
Secondary
Change in Insulin Consumption
Change in daily exogenous insulin consumption (IU)
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Arm | Change in Insulin Consumption | 0.183 IU/kg/24h | Standard Deviation 0.285 |
| Placebo Arm | Change in Insulin Consumption | 0.094 IU/kg/24h | Standard Deviation 0.342 |
| Active (HLA DR3-DQ2) | Change in Insulin Consumption | 0.143 IU/kg/24h | Standard Deviation 0.196 |
| Placebo (HLA DR3-DQ2) | Change in Insulin Consumption | 0.153 IU/kg/24h | Standard Deviation 0.399 |
Secondary
Change in Maximum C-peptide
Change in maximum C-peptide during MMTT (nmol/L)
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Arm | Change in Maximum C-peptide | -0.350 nmol/L | Standard Deviation 0.463 |
| Placebo Arm | Change in Maximum C-peptide | -0.300 nmol/L | Standard Deviation 0.35 |
| Active (HLA DR3-DQ2) | Change in Maximum C-peptide | -0.257 nmol/L | Standard Deviation 0.4 |
| Placebo (HLA DR3-DQ2) | Change in Maximum C-peptide | -0.277 nmol/L | Standard Deviation 0.349 |
Secondary
Change in Quality of Life (QoL)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active Arm | Change in Quality of Life (QoL) | Baseline | 1.000 Index value |
| Active Arm | Change in Quality of Life (QoL) | Month 15 | 1.000 Index value |
| Placebo Arm | Change in Quality of Life (QoL) | Baseline | 1.000 Index value |
| Placebo Arm | Change in Quality of Life (QoL) | Month 15 | 1.000 Index value |
Secondary
C-peptide Levels During a MMTT
C-peptide measured at 30, 60, 90, and 120 minutes during MMTT (nmol/L) at 15 months
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Arm | C-peptide Levels During a MMTT | 60 min | 0.536 nmol/L | Standard Deviation 0.383 |
| Active Arm | C-peptide Levels During a MMTT | 90 min | 0.645 nmol/L | Standard Deviation 0.495 |
| Active Arm | C-peptide Levels During a MMTT | 30 min | 0.376 nmol/L | Standard Deviation 0.295 |
| Active Arm | C-peptide Levels During a MMTT | 120 min | 0.691 nmol/L | Standard Deviation 0.542 |
| Placebo Arm | C-peptide Levels During a MMTT | 120 min | 0.590 nmol/L | Standard Deviation 0.444 |
| Placebo Arm | C-peptide Levels During a MMTT | 30 min | 0.374 nmol/L | Standard Deviation 0.33 |
| Placebo Arm | C-peptide Levels During a MMTT | 90 min | 0.562 nmol/L | Standard Deviation 0.438 |
| Placebo Arm | C-peptide Levels During a MMTT | 60 min | 0.495 nmol/L | Standard Deviation 0.411 |
| Active (HLA DR3-DQ2) | C-peptide Levels During a MMTT | 120 min | 1.065 nmol/L | Standard Deviation 0.43 |
| Active (HLA DR3-DQ2) | C-peptide Levels During a MMTT | 90 min | 1.016 nmol/L | Standard Deviation 0.415 |
| Active (HLA DR3-DQ2) | C-peptide Levels During a MMTT | 60 min | 0.911 nmol/L | Standard Deviation 0.393 |
| Active (HLA DR3-DQ2) | C-peptide Levels During a MMTT | 30 min | 0.659 nmol/L | Standard Deviation 0.352 |
| Placebo (HLA DR3-DQ2) | C-peptide Levels During a MMTT | 90 min | 0.717 nmol/L | Standard Deviation 0.318 |
| Placebo (HLA DR3-DQ2) | C-peptide Levels During a MMTT | 120 min | 0.728 nmol/L | Standard Deviation 0.317 |
| Placebo (HLA DR3-DQ2) | C-peptide Levels During a MMTT | 30 min | 0.580 nmol/L | Standard Deviation 0.282 |
| Placebo (HLA DR3-DQ2) | C-peptide Levels During a MMTT | 60 min | 0.715 nmol/L | Standard Deviation 0.308 |
Secondary
GAD65A Titer
GAD65A titer (IU/ml)
Time frame: Baseline and 15 months
Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Arm | GAD65A Titer | Baseline | 731.3 IU/mL | Standard Deviation 2302.9 |
| Active Arm | GAD65A Titer | Month 15 | 19941.2 IU/mL | Standard Deviation 23083.6 |
| Placebo Arm | GAD65A Titer | Baseline | 627.3 IU/mL | Standard Deviation 1829.9 |
| Placebo Arm | GAD65A Titer | Month 15 | 476.7 IU/mL | Standard Deviation 1527.7 |
Secondary
Injection Site Reactions
Injection site reactions
Time frame: 15 months
Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Arm | Injection Site Reactions | 10 number of episodes |
| Placebo Arm | Injection Site Reactions | 3 number of episodes |
Secondary
Number of Clinically Significant Abnormal Results From Laboratory Measurements (Haematology and Clinical Chemistry) and Urinalysis.
Number of clinically significant abnormal results from laboratory measurements (haematology and clinical chemistry) and urinalysis. (counts)
Time frame: 15 months
Population: Safety Analysis Set, consist of all randomized patients who received at least one injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Arm | Number of Clinically Significant Abnormal Results From Laboratory Measurements (Haematology and Clinical Chemistry) and Urinalysis. | 11 number of significant abnormal results |
| Placebo Arm | Number of Clinically Significant Abnormal Results From Laboratory Measurements (Haematology and Clinical Chemistry) and Urinalysis. | 3 number of significant abnormal results |
Secondary
Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations
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
Time frame: 15 months
Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active Arm | Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations | Physical examination | 15 Clinically significant abnormal results |
| Active Arm | Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations | Neurological examination | 4 Clinically significant abnormal results |
| Placebo Arm | Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations | Physical examination | 9 Clinically significant abnormal results |
| Placebo Arm | Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations | Neurological examination | 0 Clinically significant abnormal results |
Secondary
Number of Clinically Significant Abnormal Results in Vital Signs
Vital signs (blood pressure) (mmHg)
Time frame: 15 months
Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active Arm | Number of Clinically Significant Abnormal Results in Vital Signs | Diastolic blood pressure | 0 Clinically significant abnormal results |
| Active Arm | Number of Clinically Significant Abnormal Results in Vital Signs | Systolic blood pressure | 0 Clinically significant abnormal results |
| Placebo Arm | Number of Clinically Significant Abnormal Results in Vital Signs | Diastolic blood pressure | 0 Clinically significant abnormal results |
| Placebo Arm | Number of Clinically Significant Abnormal Results in Vital Signs | Systolic blood pressure | 0 Clinically significant abnormal results |
Secondary
Number of Hypoglycemias
Number of self-reported episodes of severe hypoglycemia (Severe hypoglycemia defined as needing help from others and/or seizures and/or unconscious) (counts)
Time frame: Baseline and 15 months
Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Arm | Number of Hypoglycemias | 0 Episodes |
| Placebo Arm | Number of Hypoglycemias | 6 Episodes |
| Active (HLA DR3-DQ2) | Number of Hypoglycemias | 0 Episodes |
| Placebo (HLA DR3-DQ2) | Number of Hypoglycemias | 0 Episodes |
Secondary
Number of Patients Having at Least 1 Severe Hypoglycemic Event
Number of patients having at least 1 severe hypoglycemic event (counts)
Time frame: Baseline and 15 months
Population: Safety Analysis Set, consist of all randomized patients who received at leastone injection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Arm | Number of Patients Having at Least 1 Severe Hypoglycemic Event | 0 Participants |
| Placebo Arm | Number of Patients Having at Least 1 Severe Hypoglycemic Event | 1 Participants |
| Active (HLA DR3-DQ2) | Number of Patients Having at Least 1 Severe Hypoglycemic Event | 0 Participants |
| Placebo (HLA DR3-DQ2) | Number of Patients Having at Least 1 Severe Hypoglycemic Event | 0 Participants |
Secondary
Percentage of Patients With IDAA1c ≤ 9
Percentage of patients with IDAA1c ≤ 9
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Arm | Percentage of Patients With IDAA1c ≤ 9 | 62.7 Percent of patients |
| Placebo Arm | Percentage of Patients With IDAA1c ≤ 9 | 61.4 Percent of patients |
| Active (HLA DR3-DQ2) | Percentage of Patients With IDAA1c ≤ 9 | 78.6 Percent of patients |
| Placebo (HLA DR3-DQ2) | Percentage of Patients With IDAA1c ≤ 9 | 40.0 Percent of patients |
Secondary
Stimulated C-peptide Above 0.2 Nmol/L at 90 Min
Percentage of patients with a stimulated 90min C-peptide level above 0.2 nmol/L (0.6 ng/ml)
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Arm | Stimulated C-peptide Above 0.2 Nmol/L at 90 Min | 87.3 Percent of patients |
| Placebo Arm | Stimulated C-peptide Above 0.2 Nmol/L at 90 Min | 71.4 Percent of patients |
| Active (HLA DR3-DQ2) | Stimulated C-peptide Above 0.2 Nmol/L at 90 Min | 96.6 Percent of patients |
| Placebo (HLA DR3-DQ2) | Stimulated C-peptide Above 0.2 Nmol/L at 90 Min | 64.7 Percent of patients |
Secondary
Stimulated Maximum C-peptide Above 0.2 Nmol/L
Percentage of patients with a stimulated maximum C-peptide level above 0.2 nmol/L (0.6 ng/ml)
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Arm | Stimulated Maximum C-peptide Above 0.2 Nmol/L | 92.7 Percent of patients |
| Placebo Arm | Stimulated Maximum C-peptide Above 0.2 Nmol/L | 75.7 Percent of patients |
| Active (HLA DR3-DQ2) | Stimulated Maximum C-peptide Above 0.2 Nmol/L | 96.6 Percent of patients |
| Placebo (HLA DR3-DQ2) | Stimulated Maximum C-peptide Above 0.2 Nmol/L | 70.6 Percent of patients |