E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
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 objective of this study is to determine whether intranasal administration of insulin to young children and adults at risk for type 1 diabetes (T1D) will reduce their rate of development of diabetes. |
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E.2.2 | Secondary objectives of the trial |
Secondary objective is to determine whether intranasal insulin administration to children and young adults at risk for T1D will: 1) prevent expected loss of pancreatic ß-cell function 2) improve insulin action 3) stimulate immune responses consistent with the induction of immune tolerance to insulin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. First-degree or 2nd-degree relative of person with T1D diagnosed before age 40; 2. Age 4-30 years if 1st-degree relative Age 4-20 years if 2nd-degree-relative 3. Confirmed serum antibodies to 2 or more islet antigens 4. Normal OGTT 5. FPIR at or above threshold - Primary Stratum: ≥ 10th percentile for siblings, offspring and second-degree relatives of someone with T1D (≥ 100uU/ml if aged ≥ 8 years or ≥ 60uU/ml if aged < 8 years) and ≥ 1st percentile for parents of someone with T1D (≥ 60uU/ml); Secondary Stratum: ≥ 1st <10th percentile for siblings, offspring and second-degree relatives of someone with T1D (≥ 50uU/ml <100uU/ml if aged ≥ 8 years or ≥ 20uU/ml < 60uU/ml if aged < 8 years) 6. Provision of written consent |
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E.4 | Principal exclusion criteria |
1. History of treatment with insulin or oral hypoglycaemic agents 2. Known diabetes by ADA/WHO criteria (fasting plasma glucose ³7mM or 2 hour plasma glucose in the OGTT ³ 11.1mM). 3. Pregnant or lactating, or of child-bearing potential not using a highly effective method of contraception (failure rate <1% per year when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner). 4. Concomitant disease or treatment which may interfere with assessment or cause immunosuppression, as judged by the investigators. 5. Uncorrected vitamin D deficiency (serum 25OHD <50nM). 6. Known alcohol or drug abuse, psychiatric or other condition that could be associated with poor compliance. 7. Known liver disease, or persisting elevation of plasma AST (³ 100 IU/L) or ALT (³ 110 IU/L) levels. 8. Impaired renal function (serum creatinine ³ 110uM in females or ³ 130uM in males). 9. Any defect or pathology of nasal passage which would preclude application of the intranasal spray. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The onset of diabetes, defined by ADA/WHO criteria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108 and 120 months |
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E.5.2 | Secondary end point(s) |
B-cell function assessed by the glucose and insulin responses in the OGTT Insulin resistance assessed by HOMA-R Iselt autoantibody levels and T cell responses to islet autoantigens |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108 and 120 months |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | 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 | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 1 |
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 | No |
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 |
Australia |
Germany |
New Zealand |
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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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intervention of 12 months and follow-up monitoring for at least 4 years and maximum 10 years. |
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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 | 10 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |