E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Short Stature children born small for Gestational Age (SGA) |
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E.1.1.1 | Medical condition in easily understood language |
Short stature in children born small for gestational age (SGA) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041093 |
E.1.2 | Term | Small for gestational age |
E.1.2 | System Organ Class | 10036585 - Pregnancy, puerperium and perinatal conditions |
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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 primary objective of this trial is to evaluate the efficacy of Genotropin® treatment on height SDS in short SGA children starting treatment at an age of 24-30 months as compared to untreated controls.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this trial are to evaluate the effect of Genotropin® treatment on the overall mental and psychomotor development, body weight, body mass index (BMI) and head growth as compared to untreated controls as well as to demonstrate the safety of Genotropin® treatment in young short SGA children. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Caucasian male or female subjects aged between 19-29 months at Screening Visit 1.
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
- Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
2. Born SGA (birth length and/or weight <-2 SD for gestational age, using country-specific standards).
3. Height below -2.5 SD at screening (19-35 months of age).
4. At least one measurement of length between 12 and 18 months of age.
5. Normal karyotype in girls to exclude Turners syndrome.
6. Screening laboratory values within normal limits, or abnormalities clinically insignificant in the judgement of the investigator. |
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study:
1. Severe Intra-Uterine Growth Retardation (IUGR) (birth length below - 4 SD for
gestational age), if associated with dysmorphic features.
2. Severe prematurity (Gestational Age (GA) <32 weeks of gestation).
3. Ongoing catch-up growth (defined as growth velocity SDS at inclusion >0) based on at least 4 months measurement interval).
4. Severe familial short stature defined as: Father’s height below 155 cm or mother’s height below 145 cm.
5. Defined neurological defects and/or severe neurodevelopmental delay.
6. Defined syndromes such as fetal alcohol syndrome.
7. Severe perinatal complications like asphyxia, sepsis, Necrotizing Enterocolitis (NEC), respiratory distress syndrome, if associated with long-term sequelae (like short bowel syndrome, Broncho Pulmonary Dysplasia (BPD), cerebral palsy etc).
8. Other specific reason for short stature (eg, osteochondrodysplasia).
9. Any severe, acute or chronic illness (neurological, respiratory, gastrointestinal (eg,
Coeliac disease etc) which in the opinion of the investigator may interfere with the
interpretation of safety or efficacy evaluations.
10. Will be unlikely to comply with the protocol eg, inability to return for follow-up visits, or is unlikely to complete the study.
11. Is participating in any other studies involving investigational or marketed products.
12. Is currently treated with systemic glucocorticoids or has been treated with glucocorticoids for a period of one week or longer in the past 6 months. Topical or inhaled corticosteroids are permitted.
13. Subjects receiving other hormone treatment are not eligible for this study (except stable thyroid hormone replacement).
14. Any patient who meets any contraindication specified in the Genotropin Core Data Sheet, such as hypersensitivity to the active substance or to any of the excipients or any evidence of tumor activity. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the change from baseline in height SDS after 24 months of treatment. |
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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) |
Change from baseline in height velocity SDS after 24 months of treatment.
Change from baseline in height SDS and height velocity SDS, after 12 months of treatment.
Change from baseline in mental and psychomotor development using the MDI and PDI (normalized using US ranges) of the Bayley Scale after 12 months of treatment.
Head circumference (SDS) [cm] at all time points of the study.
Change from baseline in body weight and Body Mass Index (BMI). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 and 24 months of 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 | 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) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
no active treatment, observation |
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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
| 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Austria |
Belgium |
Chile |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Ireland |
Italy |
Luxembourg |
Netherlands |
Norway |
Poland |
Russian Federation |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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 | 5 |
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 | 5 |
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 |