Type I diabetes MedDRA version: 17.0 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Product Name: DiaPep277®
Product Code: DiaPep277®
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: DiaPep277®
CAS Number: 179822-83-4
Current Sponsor code: PO-10
Sponsors
Andromeda Biotech Ltd, 42 Hayarkon st, Yavne, 81227, Israel
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject can be randomized within no more than 6 months following the diagnosis of T1D mellitus according to the ADA/WHO criteria (2010 update of ADA recommendations). To achieve this, subject should be screened up to 5 months after diagnosis. Any period of misdiagnosis with T2D or unspecified type should be included in the calculation, although the initial misdiagnosis itself is not basis for exclusion. 2. Evidence of residual beta-cell function demonstrated by basal fasting C-peptide concentrations = 0.22 nmol/L, but not more than 0.8 nmol/L. 3. The subject is positive for at least 1 diabetes-related autoantibody: IA-2A, IAA or GADA at screening. Subjects with only IAA must be no more than 1 month on insulin therapy. 4. The subject has been on insulin treatment for diabetes within 1 month since diagnosis of T1D mellitus. 5. The subject is male or female, aged 20 to 45 years, inclusive. 6. If a female of child-bearing potential, the subject is not pregnant or lactating, and will use oral hormonal contraception or other equally effective contraceptive methods throughout the study. 7. Stable medical condition for diseases, other than diabetes, during 30 days before the Screening Visit. 8. Body mass index (BMI) equal to or greater than 17 kg/m2 and not greater than 30 kg/m2 at the Screening Visit. 9. Signed informed consent to participate in the study 10. Ability to comply with all study requirements. 11. The subject is willing to initiate intensive insulin therapy (basis and bolus insulin) at study entry, or is using an insulin pump Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 474 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1 The subject has a diagnosis of latent autoimmune diabetes in adults (LADA) (Pozzilli and Di Mario 2001). 2 The subject has any significant diseases or conditions, including psychiatric disorders and substance abuse that, in the opinion of the Investigator, are likely to affect the subject's response to treatment or the ability to complete the study. 3 The subject has a prior history of any kind of malignant tumor excluding adequately treated basal cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix. 4 The subject has clinical evidence of any diabetes-related complication that in the opinion of the Investigator would interfere with the subject's participation in and/or completion of the study. 5 Subject has history of endogenous allergic reactivity: a. Severe allergic reaction or severe exacerbation of allergic asthma within 12 months prior to the Screening Visit. b. Ongoing systemic parenteral or oral steroids for asthma treatment. c. Subjects with history of life-threatening or severe allergy, re-occurrence of which cannot be ruled out based on the Investigator’s judgment. d. The subject has known allergy to lipid emulsions. 6 The subject has a known immune deficiency from any disease, or a condition associated with an immune deficiency. 7 The subject is receiving immunosuppressive or immunomodulating agents or cytotoxic therapy or any medication for more than 4 weeks that in the opinion of the Investigator might interfere with the study. 8 The subject has any of the following clinically significant laboratory abnormalities: a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than three times the upper limit of the normal (ULN) at the Screening Visit. b. Total bilirubin greater than 2 times the ULN at the Screening Visit. c. Subjects with severe renal failure at the screening visit (as defined by glomerular filtration rate 1000 mg/dL (11.3 mmol/L) at the Screening Visit. Suitable medical therapy for treatment of hyperlipidemia is allowed. 9 The subject is a known or suspected drug abuser. 10 The subject is known to test positive for HIV antibodies. 11 The subject has chronic hematologic disease. 12 The subject has liver disease such as cirrhosis or chronic active hepatitis. 13 The subject has received any investigational drug or participated in another clinical study for the indication of prevention or treatment of diabetes, at any point in the past. 14 The subject has received any investigational drug, not diabetes-related, within 1 month prior to the Baseline Visit (Visit 1). 15 The subject has already been treated with DiaPep277®. 16 The subject has had a severe blood loss (>=400 mL, e.g., blood donation) within 2 months before the first dose of the study medication. 17 The subject receives a forbidden medication (listed within section 7.2. of study protocol)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the effect of DiaPep277® versus placebo in subjects with Type 1 Diabetes Mellitus (T1D) on endogenous insulin secretion or pancreatic beta cell function as measured by AUC0-20mins calculated from C-peptide concentration vs. time curve of glucagon-stimulated test (GST).;Secondary Objective: 1. Major Clinical Endpoints: -Assess effect of DiaPep on % of subjects that achieve HbA1c=7% -Assess effect of DiaPep on % of subjects who require a daily insulin dose = 0.5 IU/kg body weight -Assess effect of DiaPep on hypoglycemic events and event rate 2. Additional Clinical Endpoints: -Assess effect of DiaPep on glycemic control (%HbA1c) at study end -Assess effect of DiaPep on daily insulin dose per body weight at study end -Assess effect of DiaPep on glycemic control according to MAGE calculated from 7 point glucose profile and CGMS data 3. Beta-cell function Endpoints - Assess effect of DiaPep on other measurements of endogenous insulin secretion: -AUC0-120 calculated from concentration vs. time curve of mixed-meal tolerance test (MMTT) C-peptide secretion -GST and MMTT peak C-peptide concentration Cmax -Percent of subjects with Cmax >= 0.2 nmol/L at end of study for GST and MMTT -Fasting C-peptide 4. Assess the safety and tolerability of DiaPep ;Primary end point(s): The primary objective of this study is to demonstrate the efficacy of DiaPep277® in subjects with newly diagnosed T1D on intensive insulin therapy, by testing the hypothesis that pancreatic beta-cell function with DiaPep277® is superior to that with placebo after 10 administrations, 24 months of treatment. The primary efficacy endpoint will be the beta-cell function, as determined by the change from baseline up to the 24-month endpoint AUC0-20min calculated from concentration-time curve of GST C-peptide secretion throughout the course of the study.;Timepoint(s) of evaluation of this end point: The primary endpoint is evaluated at Baseline, 12, and 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To demonstrate the effect of DiaPep277® on major clinical endpoints: - The percentage of subjects in the DiaPep277® group achieving the glycemic target of HbA1c = 7% compared to the placebo group. - The percentage of subjects with low daily insulin requirement in the DiaPep277® group compared to the placebo group at end of study, as determined by the number of subjects with daily insulin dose = 0.5 IU/kg body weight. - To test the hypothesis that the number or the rate of hypoglycemic events (FPG = 0.2 nmol/L, as measured after GST and/or MMTT. o Time to event Cmax<0.2 nmol/L, as measured after GST and/or MMTT. ;Timepoint(s) of evaluation of this end point: MMTT-stimulated secretion is measured at Baseline (before first administration), 18 and 25 months. The other Secondary Endpoints are evaluated at each visit (every 3 months). | — |
Countries
Argentina, Austria, Belarus, Canada, Czech Republic, Finland, Germany, Hungary, Israel, Italy, Lithuania, Poland, Romania, Russian Federation, Serbia, Spain, United States
Contacts
Public ContactEleana Spanidis
inVentiv Health Clinical Spain, S.L.
Outcome results
None listed