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 | 100000007153 |
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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 write) and 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 Anti-rhGH antibodies and E. coli host cell peptide (HCP) antibodies will be measured at baseline and visit F1. Only in the case of development of anti-rhGH antibodies or of E. coli host cell peptide (HCP) antibodies (ABs) in the previous visit follow-up measurements will be made 1, 5 and 10 years after end of treatment in study EP00-401. - Safety lab / urine analysis Hematology, blood chemistry and urine analysis will be measured at 6 months, 1, 5 and 10 years after the end of treatment in study EP00-401 unless more frequent assessment is clinically indicated - (Serious) Adverse events: Adverse events will be collected throughout the study. - Vital signs / weight: Vital signs (blood pressure, pulse) as well as weight will be examined at each visit. Efficacy endpoints: - Auxological: Height will be measured according to the usual clinical practice - Pharmacodynamic: IGF-I and IGFBP-3 serum levels will be assessed 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.8.5 | 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 |