E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Niños pre-puberales con déficit idiopático de hormona de crecimiento |
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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 |
Demostrar la mayor eficacia del tratamiento con una combinación de dosis flexibles de rhIGF-1 y 0,035 mg/kg día de rhGH sobre la velocidad del crecimiento (VC) comparada con un tratamiento de 0,035 mg/kg/día de rhGH únicamente, después de un año de tratamiento en niños prepuberales con deficiencia de IGH, que presentaron mala respuesta a la terapia con rhGH durante el primer año de tratamiento |
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E.2.2 | Secondary objectives of the trial |
Evaluar -efecto del tratamiento combinado con dosis flexibles de rhIGF1 y dosis fijas de rhGH sobre la Puntuación de la Desviación Típica (PDT) de la estatura delta. -seguridad de la combinación de dosis flexibles de rhIGF1 y dosis fijas de rhGH vs dosis fijas de rhGH. -efecto sobre las concentraciones séricas de GH y IGF-1 y sus proteínas fijadoras durante tratamiento combinado rhIGF1 y rhGH vs rhGH -efecto sobre las concentraciones séricas de la PDT del IGF1 durante tratamiento combinado rhIGF1 y rhGH vs rhGH por visita -efecto sobre el estado puberal. -cambios en la edad ósea. -Identificar factores pronósticos de respuesta terapéutica al tratamiento combinado rhIGF-1 y rhGH, sobre la base de los datos históricos, sobre las pruebas de estimulación de la GH, el IGF-1, la auxología y el diagnóstico -Evaluar los cambios en los parámetros metabólicos. |
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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) |
Una diferencia en la VC media entre los dos grupos de tratamiento después de 1 año de tratamiento. Se considera clínicamente pertinente una diferencia de ? 1,5 cm/año. |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 |
Prospectivo y multicentrico |
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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 | 8 |
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 |