E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigate 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 AUC0-120mins calculated from C-peptide concentration vs. time curve of mixed-meal tolerance test (MMTT). |
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E.2.2 | Secondary objectives of the trial |
Investigate the effect of DiaPep277® on other measurements of endogenous insulin secretion: AUC0-20 calculated from concentration vs. time curve of glucagon-stimulated C-peptide secretion; MMTT and glucagon-stimulated peak C-peptide concentration Cmax, and percent of subjects with Cmax ≥ 0.2 nmol/L at end of study.
Investigate the effect of DiaPep277® on percent of subjects that achieve HbA1c≤7%.
Investigate the effect of DiaPep277® on daily insulin dose per body weight at study end
Investigate the effect of DiaPep277® on hypoglycemic event rate
Assess the effect of DiaPep277® on glycemic control according to MAGE calculated from 7 point glucose profile and CGMS data.
Assess the safety and tolerability of DiaPep277® |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female subjects between the ages of 20 and 45 years (inclusive) at screening.
A diagnosis of T1D according to the American Diabetes Association and World Health Organization (ADA/WHO) criteria for up to 5 months at screening
A diagnosis of T1D for up to 6 months at randomization (baseline)
Subject has been on insulin since diagnosis of T1D.
Fasting C-peptide levels >= 0.22 nmol/L and <0.8 nmol/L.
Presence of at least 1 of the diabetes-related autoantibodies (IA-2A, GADA, or IAA)
Body mass index (BMI) ≥17 kg/m2 and < 30 kg/m2 at screening
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E.4 | Principal exclusion criteria |
1 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. 2 The subject has a history of any kind of malignant tumor (not including basal cell skin cancer). 3 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. 4 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 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. 5 The subject has a known immune deficiency from any disease, or a condition associated with an immune deficiency. 6 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. 7 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 < 30 mL/min/1.73 m2 by Cockroft Gault calculation (Cockcroft and Gault, 1976)). d. Clinically significant laboratory abnormalities, confirmed by repeat measurement, which may interfere with the assessment of safety and/or efficacy of the study drug, other than hyperglycemia and glycosuria at the Screening Visit. e. Fasting triglycerides >1000 mg/dL (11.3 mmol/L) at the Screening Visit. Suitable medical therapy for treatment of hyperlipidemia is allowed. 8 The subject is a known or suspected drug abuser. 9 The subject is known to test positive for HIV antibodies. 10 The subject has chronic hematologic disease. 11 The subject has liver disease such as cirrhosis or chronic active hepatitis. 12 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. 13 The subject has received any investigational drug, not diabetes-related, within 1 month prior to the Baseline Visit (Visit 1). 14 The subject has already been treated with DiaPep277®. 15 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. 16 The subject receives a forbidden medication
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E.5 End points |
E.5.1 | 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 25 months (10 administrations, 24 months of treatment, 1 month of follow-up). The primary efficacy endpoint will be the difference between placebo and DiaPep277® treatment in β-cell function, as determined by the change from baseline to the 25-month endpoint AUC0-120 calculated from concentration-time curve of MMTT-stimulated C-peptide secretion.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last subject.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |