E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed Type 1 Diabetes diagnosed within the previous three weeks at time of screening. Female and male patients between the ages of 6 and 15 years will be recruited. |
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E.1.1.1 | Medical condition in easily understood language |
In type 1 diabetes, the insulin secretion from the pancreas is insufficient to maintanin a normal blood glucose. The disease leads to increased morbidity and mortality an the causes remains unknown. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
The main study objective is to describe the influence of antiviral treatment (Pleconaril +Ribavirin) versus placebo on progression of disease and residual insulin secretion in patients diagnosed with type 1 diabetes at the age 6 -15 years. The study design a double-blind, placebo controlled, prospective, randomized trial examining the effect of antiviral treatment given for 6months on residual insulin secretion. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All of the following conditions must apply to the prospective patient at screening prior to receiving study agent:
1. Diagnosed type 1 Diabetes (E10.9). First injection of insulin maximum three weeks prior to inclusion.
2. Must be willing and capable of taking the study drugs and meet for tests and follow up as described.
3. Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
4. Aged 6-15 years at inclusion.
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E.4 | Principal exclusion criteria |
Patients will be excluded from taking part in the study if they meet any of the following criteria:
1. Treatment with any oral or injected anti-diabetic medications other than insulin or any of the study drugs.
2. A history of haemolytic anaemia or significantly abnormal haematology results at screening (Hb<11g/dl).
3. Participation in other clinical trials with a new chemical entity within the previous 3 months.
4. Inability or unwillingness to comply with the provisions of this protocol
5. Females who are lactating or pregnant. Males or females (after menarche) not willing to use adequate contraception, if sexually active, until 6 months after the last study drug administration.
6. Presence of serious disease or condition, which in the opinion of the investigator makes the patient non-eligible for the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is change in mean residual insulin secretion measured by Mixed Meal Tolerance Test (MMTT) stimulated C-peptide two-hour area under the curve profile from visit 1 to12 months after initiation of study treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months after inclusion in the study and initiation of study treatment. |
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E.5.2 | Secondary end point(s) |
The secondary end points are:
1. Change in mean residual insulin secretion measured by stimulated C-peptide two-hour area under the curve profile visit 1 to 3 months, 6 months, 24 months and 36 months
2. Proportion of patients with peak residual insulin secretion measured by MMTT: stimulated C-peptide >0,2 pmol/L.
3.Fasting and meal stimulated C-peptide from blood sampled on filter paper at home at two weekly intervals per month in 12 months and then at 4 weekly intervals
4. Mean Insulin dosage per kilo bodyweight for 24 hours one week before each control
5. HbA1c at every control
6. Number of severe hypoglycemic events
7. Insulin-dose-adjusted HbA1c (IDAA1c)
8. Proinsulin/c-peptide ratio in serum as a measure of beta cell stress
9. Change in presence of Enterovirus (PCR) in nose, blood and stool |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 months, 6 months, 24 months and 36 months after inclusion in the study and initiation of study treatment. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Add on to insulin treatment |
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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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 10 |