E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Short children born of premature gestation |
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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 |
To determine whether growth hormone therapy improves growth velocity and height SDS after one year in (very low birth weight (VLBW) preterm infants born appropriate-for-gestational age (AGA) with short stature. |
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E.2.2 | Secondary objectives of the trial |
To determine improvement of growth velocity and height SDS after two years, changes in body composition (skinfold thickness measurements), changes in bone density, bone structure and bone stability (peripheral quantitative computed tomography (pQCT)), changes in muscle strength (grip force) as well as insulin sensitivity. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Prepubertal caucasian boys between 4 and 10 years of age and girls between 4 and 9 years of age. Girls: Tanner stage 1 breast development Boys: Testis volume ≤ 3 ml Tanner stage 1 pubic hair development (to exclude confounding effect of adrenarche on growth velocity, insulin sensitivity and body composition). (In case of any signs or symptoms of gonadal puberty a GnRH-test must decide if the subject is still prepubertal)
2) Height ≤ -2 SD for chronological age (Brandt/Reinken).
3) Growth velocity SDS below 0 SD for chronological age (Brandt/Reinken based on 12 ± 3 months observation period before screening).
4) Premature born defined as ≤ 1500 g birth weight.
5) GH sufficiency (GH level >7 μg/l following any routine GH stimulation test).
6) Written informed consent of both parents (legal guardians) and oral/written consent of patient due to age specific information.
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E.4 | Principal exclusion criteria |
1) Other endocrine diseases except for well substituted hypothyroidism.
2) Severe chronic diseases or medication that might influence linear growth or insulin sensitivity (e.g. Glucocorticoids).
3) Positive GAD (Glutamatdecarboxylase, GAD65) and IA-2 (Tyrosinphosphatase) antibodies (for type 1 diabetes). (Note: A positive result of antibody determinations confirms type 1 diabetes but a negative result of GAD antibodies does not exclude type 1 diabetes).
4) History of malignancy.
5) Children who meet all of the following criteria: · actual body height <-2,5 SDS (Brandt/Reinken) and parent adjusted target height < -1 SDS (Hermanussen + Cole) · length and/or body weight retardations adjusted to gestational age at birth <-2,0 SDS (Lawrence et al., 1989, Voigt et al., 1996) · children with chronological age ≥4 years and · growth velocity < 0 SDS during the last year before inclusion.
6) Chromosomal aberrations or syndromes.
7) Suspected non-compliance or impossibility to follow the two or three year treatment schedule, respectively (e.g. social implications).
8) Severe hemiparesis and severe CNS defects.
9) Retinopathia ≥ third degree or coagulation treatment.
10) Participation in any other clinical trial during active treatment phase.
11) Other severe acute or chronic medical or psychiatric condition or clinically relevant laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgement of the investigator, would make the subject inappropriate for entry into this trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in growth velocity SDS and height SDS after one year. |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | No |
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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End of Trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the trial as stated in the regulatory application (i.e., Clinical Trial Application (CTA)) and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the trial in that Member State. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |