Type 1 Diabetes
Conditions
Keywords
C peptide, beta cell function, immune modulation of type 1 diabetes, immune intervention in type 1 diabetes
Brief summary
This is an extension study to evaluate the safety and tolerability of long-term treatment with DiaPep277® and to determine the long-term treatment effect of DiaPep277® on parameters of metabolic control and on preservation of beta-cell function in subjects who have long exposure to DiaPep277®.
Detailed description
Treatment with DiaPep277® is expected to be long-term; stopping treatment may result in the eventual loss of the preserved beta-cell function. Indeed, extension of phase 2 studies has shown that patients who were initially treated with DiaPep277® and maintained their initial beta-cell function, required continuation of treatment, losing beta-cell function if switched to Placebo. These extension studies were too small for the outcome to be statistically significant, but they suggested that continuation of treatment is needed for long-term maintenance of efficacy. Therefore, in this extension study, patients who complete the 1001 phase 3 study (NCT01103284) and maintain clinically significant beta-cell function are offered a 2-year continuation of active treatment, since they are likely to benefit from use of the medication. The participation in the extension study will be offered to all eligible subjects who complete the 1001 study, regardless of the treatment arm allocation in the initial study. By achieving long-term preservation of beta-cell function, patients are expected to maintain good management of the disease, manifesting as better glycemic control and fewer hypoglycemic events.
Interventions
DRUGDiaPep277®
1 mg of DiaPep277® subcutaneously in the upper arm at 0, 3, 6, 9, 12, 15, 18, and 21 months, for a total of 8 administrations
Sponsors
Andromeda Biotech Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 47 Years
Healthy volunteers
No
Inclusion criteria
* patients with type 1 diabetes who participated in the 1001 study * residual beta-cell function demonstrated by stimulated C-peptide ≥ 0.20 nmol/L.
Exclusion criteria
* The subject has any significant ongoing diseases or conditions that is likely to affect the subject's response to treatment * The subject has a history of any kind of malignant tumor. * The subject has clinical evidence of any diabetes-related complication * Subject has history of endogenous allergic reactivity: * The subject has a known immune deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemic Events | At Early Termination Visit, Up to 25 Months | The number of hypoglycemic events recorded by each patient over the course of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glucagon-stimulated C-peptide AUC at Early Termination Visit | Baseline and Early Termination Visit, Up to 25 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 the early termination visit (up to 25 months), during a glucagon stimulation test (GST). Change was calculated for each patient by subtracting the baseline AUC value (defined as the last non-missing assessment prior to first dose in the 1010 study but after the end of study 1001) from the early termination visit AUC. |
Other
| Measure | Time frame |
|---|---|
| Change From Baseline in Daily Insulin Dose, Per kg Body Weight, at Early Termination Visit | Baseline and Early Termination Visit, up to 25 months |
| Glycemic Control (Change From Baseline in % HbA1c) | Baseline and Early Termination Visit, Up to 25 Months |
Countries
United States
Participant flow
Recruitment details
Patients diagnosed with Type 1 diabetes mellitus up to six months before randomization to Study 1001 (NCT01103284), from medical sites in the EU, US, Russia, and Israel
Participants by arm
| Arm | Count |
|---|---|
| Patients Treated With DiaPep (Originally Enrolled in Study1001 All patients enrolled in the 1010 study (NCT01898286), whether previously treated with DiaPep277 or placebo in the 1001 study (NCT01103284). | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Patients Treated With DiaPep (Originally Enrolled in Study1001 |
|---|---|
| Age, Continuous | 33.16 years STANDARD_DEVIATION 7.343 |
| Age, Customized | 32.00 years |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Black | 3 participants |
| Race/Ethnicity, Customized Caucasian | 33 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 38 |
| serious Total, serious adverse events | 1 / 38 |
Outcome results
Primary
Hypoglycemic Events
The number of hypoglycemic events recorded by each patient over the course of the study.
Time frame: At Early Termination Visit, Up to 25 Months
Population: Patients with hypoglycemic event data at the time of their early termination visit. This population is smaller than the population numbers in the patient flow categories because not all patients were willing to provide information on hypoglycemic events at early termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Treated With DiaPep (Originally Enrolled in Study1001 | Hypoglycemic Events | 3.3 hypoglycemic events | Standard Deviation 3.3 |
Secondary
Change From Baseline in Glucagon-stimulated C-peptide AUC at Early Termination Visit
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 the early termination visit (up to 25 months), during a glucagon stimulation test (GST). Change was calculated for each patient by subtracting the baseline AUC value (defined as the last non-missing assessment prior to first dose in the 1010 study but after the end of study 1001) from the early termination visit AUC.
Time frame: Baseline and Early Termination Visit, Up to 25 Months
Population: Only 9 patients had sufficient data for this analysis, as many patients declined to undergo the GST at the termination visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Treated With DiaPep (Originally Enrolled in Study1001 | Change From Baseline in Glucagon-stimulated C-peptide AUC at Early Termination Visit | 0.2 nmol*minute/L | Standard Deviation 2.334 |
Other Pre-specified
Change From Baseline in Daily Insulin Dose, Per kg Body Weight, at Early Termination Visit
Time frame: Baseline and Early Termination Visit, up to 25 months
Population: All patients with daily insulin dose data at baseline and their early termination visit. Only 11 patients could be included in this analysis, as not all patients provided insulin dose data at their early termination visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Treated With DiaPep (Originally Enrolled in Study1001 | Change From Baseline in Daily Insulin Dose, Per kg Body Weight, at Early Termination Visit | 0.025 IU/kg | Standard Deviation 0.027 |
Other Pre-specified
Glycemic Control (Change From Baseline in % HbA1c)
Time frame: Baseline and Early Termination Visit, Up to 25 Months
Population: All patients with % HbA1c data at baseline and their early termination visit. Only 5 patients were available for this analysis, as not all patients agreed to complete HbA1c testing at the early termination visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Treated With DiaPep (Originally Enrolled in Study1001 | Glycemic Control (Change From Baseline in % HbA1c) | 0.46 % HbA1c | Standard Deviation 0.907 |