E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Growth disturbance (current height standard deviation score (SDS) < -2.5 and parental adjusted SDS < -1) in short children born small for gestational age (SGA), with a birth weight and/or length below -2 standard deviation (SD), who failed to show catch-up growth (height velocity (HV) SDS < 0 during the last year) by 4 years of age or later |
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E.1.1.1 | Medical condition in easily understood language |
Short children born small for gestational age |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018747 |
E.1.2 | Term | Growth hormone |
E.1.2 | System Organ Class | 100000004848 |
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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 |
To evaluate the long-term effect of growth hormone treatment on the development of diabetes in short children born SGA for 10 years after the end of treatment. |
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E.2.2 | Secondary objectives of the trial |
- To report the incidence of anti-rhGH antibodies (ABs) 6 months after termination of growth hormone treatment. - To evaluate final height in follow-up period. - To evaluate IGF-I and IGFBP-3 levels for 10 years after end of growth hormone treatment. - To evaluate incidence and severity of adverse events.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. All patients who fulfilled the diagnosis SGA, participated in study EP00-401, and received at least one dose of study medication. 2. Written informed patient of patient (for children who can read and/or write) and/or parent or legal guardian. |
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E.4 | Principal exclusion criteria |
1. Patients unwilling and/or parents/guardians who are not capable of ensuring compliance with the provisions of the study protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints: - Carbohydrate metabolism: Fasting plasma glucose and insulin levels will be measured 6 months, 1, 5 and 10 years after the end of treatment in study EP00-401. Glycosylated haemoglobin (HbA1C) will be measured 6 months, 1, 5 and 10 years after the end of treatment in study EP00-401. An oral glucose tolerance test (OGTT) will be performed 6 months, 1, 5 and 10 years after the end of treatment in study EP00-401. - Immunogenicity Subjects will be screened for anti-rhGH antibodies (ABs) 6 months after treatment. Only in case of positive antibodies measurements in previous visit follow-up measurements are planned after 1 year, 5 years and 10 years. - Additional safety criteria: Additional criteria for assessing safety will consist of monitoring and recording all adverse events, vital signs and body weight, physical condition, haematology, blood chemistry, thyroid function tests, lipids and urinalysis. Adverse events, body weight and physical condition will be assessed at every study visit. Laboratory tests for safety will be performed, 6 months, 1, 5 and 10 years after the end of treatment. - Vital signs / weight: Vital signs (blood pressure and pulse rate) will be recorded at each visit in a standardised manner, i.e., after the patient has rested for five minutes in the sitting position. Weight will be measured according to the usual clinical practice. Efficacy endpoints: - Auxological: Patients' height will be measured at each visit. - Pharmacodynamic: IGF-I and IGFBP-3 serum levels will be assessed by a central laboratory 6 months, 1, 5 and 10 years after the end of treatment in study EP00-401. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Interim analyses are planned at the following time points: • 2022 with data of patients who completed 1 year of follow-up • 2026 with data of patients who completed 5 years of follow-up • 2031 with data of patients who completed 10 years of follow-up |
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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 | No |
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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Belgium |
Czech Republic |
Georgia |
Germany |
Hungary |
Poland |
Romania |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 25 |
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 | 25 |
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 |