Type 1 Diabetes
Conditions
Brief summary
The purpose of this study is to determine if DiaPep277 can effectively protect the internal production of insulin in patients newly diagnosed with type 1 diabetes, by stopping the immune destruction of insulin-producing beta-cells in the pancreas. DiaPep277 acts on the immune system and is expected to prevent further destruction of the beta-cells by stimulating regulatory responses, without causing immunological suppression.
Interventions
DRUGDiaPep277
1.0mg dose, administered as subcutaneous injection, on 0, 1, 3, 6, 9, 12, 15, 18 and 21 months
DRUGPlacebo
Mannitol (excipient) 40 mg, administered as subcutaneous injection on 1, 3, 6, 9, 12, 15, 18 and 21 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
16 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* A diagnosis of type 1 diabetes for up to 3 months at screening * Insulin dependency * Fasting C-peptide levels \>= 0.22 nmol/L * Presence of at least 1 of the diabetes-related autoantibodies (IA-2A, GAD or IA)
Exclusion criteria
* Pregnancy or intent to conceive in the next 2 years * Significant diseases that could affect response to treatment, such as tumors, psychiatric disorders, substance abuse, severe allergies or diabetes-related complications. * Patient has immune deficiency or receives immuno-suppressive or cytotoxic drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glucagon-stimulated C-peptide AUC at 24 Months | Baseline and 24 months | Beta-cell function, measured as change in stimulated C-peptide secretion measured 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 |
|---|---|---|
| Change From Baseline in Mixed-meal Stimulated C-peptide AUC at 24 Months | Baseline and 24 Months | Beta cell function, measured as stimulated C-peptide secretion from 0 to 120 min post administration AUC, at baseline and 24 month measurements in a mixed-meal tolerance test (MMTT). The change in AUC was calculated per patient by subtracting the baseline AUC from the 24 month AUC. |
Countries
Austria, Czechia, Finland, France, Germany, Greece, Israel, Italy, South Africa, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DiaPep277 DiaPep277 1.0 mg + 40 mg Mannitol in 0.5mL Lipid emulsion.
DiaPep277: 1.0 mg dose, administered as subcutaneous injection, on 0, 1, 3, 6, 9, 12, 15, 18 and 21 months | 225 |
| Placebo Mannitol 40 mg in 0.5 mL Lipid emulsion.
Placebo: Mannitol (excipient) 40 mg, administered as subcutaneous injection on 1, 3, 6, 9, 12, 15, 18 and 21 months. | 231 |
| Total | 456 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 5 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Dermal Hypersensitivity | 0 | 3 |
| Overall Study | Lost to Follow-up | 6 | 13 |
| Overall Study | Not defined | 7 | 4 |
| Overall Study | Protocol Violation | 11 | 7 |
| Overall Study | Withdrawal by Subject | 17 | 19 |
Baseline characteristics
| Characteristic | Placebo | DiaPep277 | Total |
|---|---|---|---|
| Age, Continuous | 26.4 years STANDARD_DEVIATION 7.85 | 26.6 years STANDARD_DEVIATION 7.99 | 26.5 years STANDARD_DEVIATION 7.91 |
| Age, Customized | 26.0 years | 25.0 years | 25.0 years |
| Race/Ethnicity, Customized Asian | 4 participants | 1 participants | 5 participants |
| Race/Ethnicity, Customized Black | 7 participants | 6 participants | 13 participants |
| Race/Ethnicity, Customized Caucasian | 212 participants | 212 participants | 424 participants |
| Race/Ethnicity, Customized Oriental | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Other | 7 participants | 4 participants | 11 participants |
| Sex: Female, Male Female | 73 Participants | 83 Participants | 156 Participants |
| Sex: Female, Male Male | 158 Participants | 142 Participants | 300 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 173 / 225 | 164 / 231 |
| serious Total, serious adverse events | 26 / 225 | 14 / 231 |
Outcome results
Primary
Change From Baseline in Glucagon-stimulated C-peptide AUC at 24 Months
Beta-cell function, measured as change in stimulated C-peptide secretion measured 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: Modified Intent to Treat (MITT) Population - all randomized patients who received at least one dose of study medication and who entered the study according to the definition of the target population, as defined by the inclusion and exclusion criteria in the study protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DiaPep277 | Change From Baseline in Glucagon-stimulated C-peptide AUC at 24 Months | -3.848 nmol*minute/L | Standard Error 0.4666 |
| Placebo | Change From Baseline in Glucagon-stimulated C-peptide AUC at 24 Months | -4.348 nmol*minute/L | Standard Error 0.4584 |
p-value: 0.2851Mixed Models Analysis
Secondary
Change From Baseline in Mixed-meal Stimulated C-peptide AUC at 24 Months
Beta cell function, measured as stimulated C-peptide secretion from 0 to 120 min post administration AUC, at baseline and 24 month measurements in a mixed-meal tolerance test (MMTT). 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: Modified Intent to Treat (MITT) Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DiaPep277 | Change From Baseline in Mixed-meal Stimulated C-peptide AUC at 24 Months | -44.33 nmol*minute/L | Standard Error 3.6884 |
| Placebo | Change From Baseline in Mixed-meal Stimulated C-peptide AUC at 24 Months | -43.24 nmol*minute/L | Standard Error 3.5898 |
p-value: 0.769Mixed Models Analysis