E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pre-Pubertal Children with Idiopathic Growth Hormone Deficiency |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056438 |
E.1.2 | Term | Growth hormone deficiency |
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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 demonstrate a superior efficacy on height velocity (HV) of treatment with a combination of flexible rhIGF-1 dose and 0.035 mg/kg/day of rhGH, as compared to treatment with 0.035 mg/kg/day of rhGH only, after one year of treatment in pre-pubertal children with IGHD, showing a poor response to rhGH treatment during the first treatment year. |
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E.2.2 | Secondary objectives of the trial |
• To assess: - effect on HV, delta height SDS, HV SDS of flexible rhIGF-1 dose and fixed rhGH dose combination therapy vs. fixed rhGH dose therapy - safety of flexible rhIGF-1 dose and fixed rhGH dose combination vs. fixed rhGH dose therapy - effect on serum concentrations of GH and IGF-1 and their binding proteins during flexible rhIGF-1 dose and fixed rhGH dose combination therapy vs. fixed rhGH dose therapy - effect on serum concentrations of IGF-1 SDS during flexible rhIGF-1 dose and fixed rhGH dose combination therapy vs. fixed rhGH dose therapy at each visit - effect on pubertal status - change in bone age • To identify prognostic factors of therapeutic response to flexible rhIGF-1 dose and fixed rhGH combination therapy, based on historical data (pre rhGH treatment and at study start), on GH stimulation tests, IGF-1, auxology and diagnosis • To assess changes in metabolic parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Treatment with rhGH at a minimum starting dose of 0.025 mg/kg/day (without dose reduction) to a maximum dose of 0.035 mg/kg/day for at least 12 months and a maximum of 18 months based on the diagnosis of IGHD with a pre-treatment GH stimulation test/spontaneous maximum of GH < 10µg/L • First year of rhGH treatment resulting in height gain < 0.5 SDS • Chronological age from 3 to 9 years inclusive for girls, from 3 to 10 years inclusive for boys • Pre-pubertal: Tanner stage 1 (Girls: Tanner B1, Boys: Testis ≤ 3ml) • Parent(s)/guardian(s) have provided written informed consent |
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E.4 | Principal exclusion criteria |
• Evidence (more than 20% rhGH injections missed) or suspicion of poor compliance during the first year of rhGH treatment • Hypothalamic-pituitary tumours diagnosed or treated prior to screening • Evidence of any active malignancy or intracranial tumours • Co-morbidity known to affect linear growth including, but not limited to, skeletal dysplasia • Chronic illness including but not limited to diabetes, inborn errors of metabolism, osteochondrodystrophy, disorders of genitourinary, cardiopulmonary, gastrointestinal, or central nervous system • Any named syndrome known to be associated with short stature but not limited to Prader-Willi syndrome, Russel Silver syndrome, etc. • Neurological disease and mental disabilities that may interfere with compliance [Attention Deficit Hyperactivity Disorders (ADHD), autism, Asperger] • Ongoing drug treatment known to alter growth, including but not limited to high dose glucocorticoids • Multiple hormonal deficiencies except hypothyroidism if corrected and well controlled • Abnormal findings at previous fundoscopy or echocardiogram • Significant abnormality in clinical screening laboratories, as determined by the Investigator • Syndromes that predispose the subject to cancer (e.g. Fanconi syndrome, Bloom syndrome, ataxia telangectasia) • Active seizure disorders, defined as one or more seizures per month irrespective of anticonvulsant therapy • Known allergy or hypersensitivity to any components of NutropinAq® (somatropin) or Increlex® (mecasermin) • Acute critical illness due to complications following open heart or abdominal surgery, multiple accidental traumas or acute respiratory failure • Any current or previous exposure to therapeutic spinal irradiation • Prior bone marrow transplantation • Evidence of clinical malnutrition or growth deficit attributable to emotional deprivation • Participation in a clinical trial within the last 12 weeks • Any social or medical condition that, in the opinion of the Investigator, would be detrimental to either the subject or the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in mean HV between the two treatment groups after 1 year of treatment. A difference of ≥ 1.5 cm/year is considered to be clinically relevant. |
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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) | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Prospective and multi-centre |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
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 | 3 |
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 |