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 | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
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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 patients with Type 1 Diabetes Mellitus (T1D) on pancreatic beta-cell function as measured by stimulated C-peptide secretion. |
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E.2.2 | Secondary objectives of the trial |
Critical Secondary: • Investigate the effect of DiaPep277™ on daily insulin dose /body weight at study end • Investigate the effect of DiaPep277™ on hypoglycemic event rate Exploratory Secondary: • Assess the effect of DiaPep277™ on metabolic control • Other parameters for Beta-cell function • Immunological response • Assess the safety and tolerability of DiaPep277™
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients meeting all of the following inclusion criteria at screening should be considered for admission to the study: 1. The patient has a diagnosis of T1D mellitus according to the ADA/WHO for up to 3 months. 2. Evidence of residual beta-cell function demonstrated by basal fasting C-peptide concentrations ≥ 0.22 nmol/L. 3. Presence of 1 or more of the following criteria: • at least 1 diabetes-related autoantibody: IA-2, insulin or GAD at screening; • and/or: age at diagnosis < 20 years and ketonuria at diagnosis. 4. The patient is on insulin treatment for diabetes since diagnosis. 5. The patient is male or female, aged 16 to 45 years, inclusive. 6. If a female of child-bearing potential, the patient 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 screening visit. 8. Body mass index (BMI) equal to or greater than 17 kg/m2 and not greater than 28 kg/m2 at screening visit 9. Signed informed consent to participate in the study 10. Ability to comply with all study requirements. 11. The patient is on intensive insulin therapy (basis/bolus insulin) or is willing to initiate intensive insulin therapy or is using an insulin pump. Patients meeting the following inclusion criteria at baseline visit (visit 1) are considered eligible for randomization: 1. The patient has a diagnosis of T1D mellitus according to the ADA/WHO for up to 4 months. 2. The patient has NOT • had mean blood glucose levels > 200 mg/dl during any 3 days within the week before baseline visit • ketoacidosis • Ketonuria on urine stix testing (+)
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E.4 | Principal exclusion criteria |
Patients meeting any of the following exclusion criteria at screening will not be enrolled in the study. 1. The patient is treated with inhaled insulin. 2. The patient has had unintentional/unplanned weight loss of ≥ 10 percent of body weight within the previous 6 months. 3. The patient has any significant diseases or conditions, including psychiatric disorders and substance abuse that, in the opinion of the Investigator, are likely to affect the patient's response to treatment or the ability to complete the study. 4. The patient has a history of any kind of malignant tumor (not including basal cell skin cancer). 5. The patient has clinical evidence of any diabetes-related complication that in the opinion of the Investigator would interfere with the patient's participation in and/or completion of the study. 6. Patient has history of endogenous allergic reactivity: • Severe allergic reaction or severe exacerbation of allergic asthma within 12 months prior to screening visit. • Ongoing systemic asthma treatment. • Patients with history of life threatening or severe allergy, re-occurrence of which cannot be ruled out based on the Investigator’s judgment. 7. The patient has known allergy to lipid emulsions. 8. The patient has a known immune deficiency from any disease, or a condition associated with an immune deficiency. 9. The patient is receiving immunosuppressive or immunomodulating agents or cytotoxic therapy, or any medication that, in the opinion of the Investigator, might interfere with the study. 10. The patient has any of the following clinically significant laboratory abnormalities: • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than three times the upper limit of the normal (ULN) at the screening visit. • Total bilirubin greater than 1.3 times the ULN at the screening visit. • Patients with severe renal failure at the screening visit (as defined by glomerular filtration rate < 30 mL/min/1.73 m2 by Cockroft und Gault calculation [13]) • Clinically significant laboratory abnormalities, confirmed by repeat measurement, that may interfere with the assessment of safety and/or efficacy of the study drug, other than hyperglycemia and glycosuria at the screening visit. • Fasting triglycerides > 1000 mg/dL (11.3 mmol/L) at the screening visit. Suitable medical therapy for treatment of hyperlipidemia is allowed. 11. The patient is a known or suspected drug abuser. 12. The patient is known to test positive for HIV antibodies. 13. The patient has chronic hematologic disease. 14. The patient has liver disease such as cirrhosis or chronic active hepatitis. 15. The patient has received any investigational drug within 3 months prior to Visit 1. 16. The patient has already been treated with DiaPep277TM. 17. The patient has had a severe blood loss (≥ 400 mL, e.g., blood donation) within 2 months before the first dose of the study medication. For forbidden prior and concomitant medications/treatments please refer to section 8.2.
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E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate the efficacy of add-on therapy with DiaPep277™ in patients 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 24 months (9 administrations, 21 months treatment, 3 months follow up) Primary efficacy endpoint will be the difference in beta-cell function between Placebo and DiaPep277® treated, as determined by change from baseline in stimulated C-peptide(AUC 0-120 min) secretion. Two tests will be used to measure beta-cell function: the 2-hour MMTT and the I.V. glucagon test. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
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 | 27 |
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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |