E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Growth disturbance (current height SDS < -2.5 and parental adjusted height SDS < -1) in short children born small for gestational age (SGA), with a birth weight and/or length below -2 SD, who failed to show catch-up growth (HV SDS < 0 during the last year) by 4 years of age or later. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041093 |
E.1.2 | Term | Small for gestational age |
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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 |
Primary objective is to determine whether growth hormone therapy improves motor- performance and coordinative skills in pre-pubertal individuals with SGA as defined by efficiency of muscular function. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to determine positive effects of growth hormone on cognitive performance (especially attention, alertness and memory), motor performance and coordinative skills as defined by peak jump power, peak jump force and maximal jump velocity, increment in muscle strength (dynamometer), changes in body composition (skinfold thickness measurements), changes in height SDS and growth velocity SDS. Furthermore, it should be demonstrated that growth hormone therapy in SGA children is safe and no new or unexpected side effects compared to the classical indications are probable.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Pre-pubertal boys between 6 and 10 years of age or girls between 6 and 9 years of age 2. Birth length- and/or birth weight-SDS adjusted to gestational age < -2.0 (Voigt et al. 2002, Voigt et al. 2006 or Lawrence et al. 1989) 3. Current height-SDS < -2.5 (Brandt/Reinken 1992) and parental adjusted height-SDS < -1 (Hermanussen and Cole 2003) 4. Growth velocity SDS < 0 during the last year before inclusion (Brandt/Reinken 1988) 5. Girls: Tanner stage 1 breast development (Tanner 1962) 6. Boys: Testis volume ≤ 3 ml (Prader 1966) 7. Tanner stage 1 pubic hair development (to exclude confounding effect of adrenarche on growth velocity, insulin sensitivity and body composition) 8. Evidence of a personally signed and dated informed consent document indicating that both parents of the subject (both legally acceptable representatives) has been informed of all pertinent aspects of the study and oral/written consent of subject due to age specific information has been obtained 9. Subject (and a legally acceptable representative) is willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
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E.4 | Principal exclusion criteria |
1. Severe SGA (birth weight or length < -4 SD) and clinically relevant dysmorphic features 2. Severe pre-maturity (GA < 32 weeks of gestation) 3. Severe perinatal complications like asphyxia, sepsis, necrotizing enterocolitis (NEC), respiratory distress syndrome, if associated with long-term sequelae (like short bowel syndrome, bronchopulmonary dysplasia (BPD), cerebral palsy etc) 4. Inability to perform one- or two leg jumps from a standing position 5. Prior GH treatment 6. Other endocrine diseases except for well substituted hypothyroidism (stable replacement therapy for at least 3 months prior to randomization) 7. Any severe acute or chronic diseases (neurological, respiratory, gastrointestinal etc) or medication that might influence linear growth, cognitive performance or insulin sensitivity (e.g. prednisolone for more than 7 days in doses above 10 mg per day or other per oral glucocorticosteroids in equivalent doses are not permitted throughout the trial. Treatment with topical or inhaled steroids is permitted). Individuals should not be under treatment of musculoskeletal diseases. Moreover, the administration of neuropharmacological and psychopharmacological drugs is not allowed (including methylphenidate, atomoxetin) 8. Known diabetes mellitus 9. Active malignancy/tumor or history of malignancy/tumor disease 10. Turner syndrome in girls 11. Other defined chromosomal aberrations or syndromes (e.g. fetal alcohol syndrome, osteochondrodysplasia), except Silver-Russell syndrome 12. Suspected non-compliance or impossibility to follow the treatment schedule, respectively (e.g. social implications) 13. Defined neurological defects, e.g. paresis, severe microcephaly 14. Severe non-corrected impaired vision 15. Ongoing psychotherapy 16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study 17. Participation in any other study during active treatment phase 18. Any other contraindications and warnings referring to the SGA indication and referenced in the actual local SmPC version of Genotropin®
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E.5 End points |
E.5.1 | Primary end point(s) |
• Changes in efficiency of muscular function (Emf) after six months (two-leg-jump; Leonardo jump plate)(hierarchic testing) |
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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 | 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 | 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 |
treated vs untreated group during 6 month study period |
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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 | 14 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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See protocol, chapter 13. |
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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 | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |