Type 1 Diabetes Mellitus
Conditions
Keywords
beta-cells, autoimmune, Diabetes, immunomodulation
Brief summary
This study will look at the treatment effect of DiaPep277 on preservation of beta-cell function, as defined by meal-stimulated secretion of insulin. DiaPep277 is a peptide that changes the way the immune system behaves, stopping its attack on the beta-cells. Adults (\>20 years) with newly diagnosed (\<6 months) type 1 diabetes will be treated with 10 injections of DiaPep277 or Placebo over a 2-year treatment and follow-up period.
Interventions
DRUGDiaPep277
1.0 mg dose in 0.5 mL of solution
DRUGPlacebo
40 mg mannitol in 0.5 mL of solution. Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months
Sponsors
Andromeda Biotech Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* clinical diagnosis of type 1 diabetes within last 6 months * Age 20-45 years * fasting basal C-peptide equal or greater than 0.22 nmol/L, lower than 0.8 nmol/L * BMI between 17 and 30 at screening
Exclusion criteria
* Significant disease or condition other than type 1 diabetes * Diabetes-related complications * Ongoing treatment with immunosuppressive or immunomodulating agents including chronic corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glucagon-Stimulated C-Peptide AUC at 24 Months | Baseline and 24 months | Change in Beta-cell function, measured as stimulated C-peptide secretion 0, 2, 6, 10 and 20 minutes post administration \[area under the curve (AUC), 0-20 minutes\] at baseline and 24 months, during a glucagon stimulation test (GST). The change in AUC was calculated per patient by subtracting the baseline AUC from the 24 month AUC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects That Achieve Good Glycemic Control: HbA1c<7% | 24 and 25 months | The percentage of subjects achieving good glycemic control, i.e. an HbA1c \<7% at study end (Month 25). If HbA1c was missing at Month 25, but the Month 24 value was available, then the Month 24 value was used to calculate the percentage of subjects with an HbA1c ≤ 7% at study end. |
| Frequency of Hypoglycemic Events | Baseline to 25 Months | Total number of days with at least one hypoglycemic event recorded |
| Mean Number of Days With at Least One Hypoglycemic Event | Baseline to 25 months | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Requiring a Daily Insulin Dose ≤ 0.5 IU/kg at End of Study | 24 and 25 months | Percentage of subjects requiring a daily insulin dose ≤ 0.5 IU/kg at end of study (25 Months). If insulin dose was missing at Month 25, but the Month 24 value was available, then the Month 24 value was used to calculate the percentage of subjects with a daily insulin dose ≤ 0.5 IU/kg at study end. |
Countries
Austria, Belarus, Canada, Czechia, Finland, Germany, Hungary, Israel, Italy, Lithuania, Poland, Russia, Spain, United States
Participant flow
Recruitment details
Patients newly diagnosed with Type 1 diabetes were recruited at medical centers in the US, EU, Argentina, and Israel.
Participants by arm
| Arm | Count |
|---|---|
| DiaPep277 Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.
DiaPep277: 1.0 mg dose in 0.5 mL of solution | 236 |
| Placebo Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.
Placebo: 40 mg mannitol in 0.5 mL of solution.
Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months | 238 |
| Total | 474 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Dermal Hypersensitivity | 0 | 1 |
| Overall Study | Lost to Follow-up | 9 | 10 |
| Overall Study | Missing CRF entries for study completion | 0 | 2 |
| Overall Study | Not described | 2 | 1 |
| Overall Study | Pregnancy | 3 | 1 |
| Overall Study | Protocol Violation | 12 | 5 |
| Overall Study | Termination by the Sponsor | 0 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 18 |
Baseline characteristics
| Characteristic | DiaPep277 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 28.7 years STANDARD_DEVIATION 6.75 | 28.5 years STANDARD_DEVIATION 6.56 | 28.6 years STANDARD_DEVIATION 6.65 |
| Age, Customized | 27.0 years | 27.0 years | 27.0 years |
| Daily Insulin Dose | 0.305 IU/kg/day STANDARD_DEVIATION 0.1587 | 0.317 IU/kg/day STANDARD_DEVIATION 0.1649 | 0.311 IU/kg/day STANDARD_DEVIATION 0.1618 |
| Fasting C-Peptide | 0.388 nmol/L STANDARD_DEVIATION 0.1473 | 0.407 nmol/L STANDARD_DEVIATION 0.1731 | 0.398 nmol/L STANDARD_DEVIATION 0.1609 |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Caucasian | 224 participants | 225 participants | 449 participants |
| Race/Ethnicity, Customized Hispanic | 6 participants | 6 participants | 12 participants |
| Race/Ethnicity, Customized Oriental | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Other | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Unknown | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 79 Participants | 73 Participants | 152 Participants |
| Sex: Female, Male Male | 157 Participants | 165 Participants | 322 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 171 / 236 | 172 / 238 |
| serious Total, serious adverse events | 15 / 236 | 10 / 238 |
Outcome results
Primary
Change From Baseline in Glucagon-Stimulated C-Peptide AUC at 24 Months
Change in Beta-cell function, measured as stimulated C-peptide secretion 0, 2, 6, 10 and 20 minutes post administration \[area under the curve (AUC), 0-20 minutes\] at baseline and 24 months, during a glucagon stimulation test (GST). The change in AUC was calculated per patient by subtracting the baseline AUC from the 24 month AUC.
Time frame: Baseline and 24 months
Population: Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DiaPep277 | Change From Baseline in Glucagon-Stimulated C-Peptide AUC at 24 Months | -5.20 nmol*min/L | Standard Error 0.27 |
| Placebo | Change From Baseline in Glucagon-Stimulated C-Peptide AUC at 24 Months | -4.83 nmol*min/L | Standard Error 0.3 |
p-value: 0.33Mixed Models Analysis
Secondary
Frequency of Hypoglycemic Events
Total number of days with at least one hypoglycemic event recorded
Time frame: Baseline to 25 Months
Population: Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DiaPep277 | Frequency of Hypoglycemic Events | 1955 days |
| Placebo | Frequency of Hypoglycemic Events | 3264 days |
Secondary
Mean Number of Days With at Least One Hypoglycemic Event
Time frame: Baseline to 25 months
Population: Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DiaPep277 | Mean Number of Days With at Least One Hypoglycemic Event | 13.0 days | Standard Error 2.3 |
| Placebo | Mean Number of Days With at Least One Hypoglycemic Event | 35.4 days | Standard Error 7.6 |
Comparison: The number of hypoglycemia events during the study was analyzed using a negative binomial regression model, with number of events as the dependent variable, and treatment, age, baseline daily insulin dose, and baseline C-peptide as covariates. The log of duration in the study for each patient was used as an offset variable in the model.p-value: 0.0795% CI: [-0.02, 0.79]negative binomial regression
Secondary
Percentage of Subjects That Achieve Good Glycemic Control: HbA1c<7%
The percentage of subjects achieving good glycemic control, i.e. an HbA1c \<7% at study end (Month 25). If HbA1c was missing at Month 25, but the Month 24 value was available, then the Month 24 value was used to calculate the percentage of subjects with an HbA1c ≤ 7% at study end.
Time frame: 24 and 25 months
Population: Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DiaPep277 | Percentage of Subjects That Achieve Good Glycemic Control: HbA1c<7% | 47 percentage of subjects |
| Placebo | Percentage of Subjects That Achieve Good Glycemic Control: HbA1c<7% | 47 percentage of subjects |
p-value: 0.68Mixed Models Analysis
Other Pre-specified
Percentage of Subjects Requiring a Daily Insulin Dose ≤ 0.5 IU/kg at End of Study
Percentage of subjects requiring a daily insulin dose ≤ 0.5 IU/kg at end of study (25 Months). If insulin dose was missing at Month 25, but the Month 24 value was available, then the Month 24 value was used to calculate the percentage of subjects with a daily insulin dose ≤ 0.5 IU/kg at study end.
Time frame: 24 and 25 months
Population: Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DiaPep277 | Percentage of Subjects Requiring a Daily Insulin Dose ≤ 0.5 IU/kg at End of Study | 63 percentage of subjects |
| Placebo | Percentage of Subjects Requiring a Daily Insulin Dose ≤ 0.5 IU/kg at End of Study | 57 percentage of subjects |
p-value: 0.44Mixed Models Analysis