E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic short stature (ISS) |
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E.1.1.1 | Medical condition in easily understood language |
Growth failure seen in children |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Demonstrate that an individualized, formula-based Genotropin regimen for children with ISS would lead to a targeted height gain (to reach the target of 10th percentile (%), or -1.3 standard deviation score [SDS]) during 24 months of treatment. |
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E.2.2 | Secondary objectives of the trial |
1. More uniformly achieve the desired height gain at 24 months with the goal of minimizing the variability between subjects.
2. Demonstrate the safety of Genotropin treatment with this treatment paradigm.
3. Identify pharmacogenomic variants related to growth/stature.
4. Explore treatment efficiency over 4 years of 2 formula-based dose regimens (sub-arms) compared to standard treatment.
5. Explore maintained treatment efficacy at 4 years of 2 formula-based dose regimens (sub-arms) compared to standard treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Pre pubertal children with bone ages between 3 and 10 years of age for males and 3 and 9 years of age for females (maximum age is lower in females as females typically have less growth potential at the same chronological age, and it is desired to minimize this difference).
2. Height between 2.25 and 3.0 Standard Deviations (SD’s) below the mean.
3. Growth velocity below the 25 th percentile (-0.67 SD) for bone age.
4. Peak Growth hormone (GH) stimulation testing greater than or equal to (>=) 10 nanogram per milliter (ng/ml).
5. Normal karyotype in females.
6. Naïve to GH treatment.
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E.4 | Principal exclusion criteria |
Abnormal karyotype.
Small for gestational age (SGA)
Documented resistance to recombinant human growth hormone(rhGH) /primary Insulin like growth factor (IGF1) deficiency.
Skeletal dysplasia.
Chronic diseases (except for well controlled hypothyroidism).
Excessive corticosteroid use.
1. More than (>)200 microgram(mcg)/day inhaled corticosteroids (fluticasone or budesonide or equivalent)
2. >= 4 episodes of oral corticosteroids (at supraphysiologic doses) per year
3. Inability to comply with research study requirements.
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute On-target Difference (AOTD) at 24 Months |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Variability of Height SDS at 24 Months
2) Time Cost (Months Until >= -2 SDS)
3) Computed Cost of Height Gain at 48 Months
4) Estimated Cost of Height Gain Estimated Until Full Adult Height (FAH) at 48 Months
5) Change From Baseline in Height SDS at 48 Months. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 2 years
2) 2 years
3) 4 years
4) 4 years
5) 4 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
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 | Information not present in EudraCT |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 25 |