E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Children with growth failure associated with primary insulin-like growth factor deficiency (IGFD). |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
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 |
The primary objective of the study is to demonstrate the safety and efficacy of rhIGF-1 in promoting the growth of children with growth failure associated with Primary IGFD. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to:
1. Demonstrate the dose-response relationship between rhIGF-1 and linear growth in prepubertal children
2. Identify a dose range with an acceptable risk-to-benefit profile
3. Assess the treatment-outcome predictive powers of an IGF generation test |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- IGF-1 deficiency as evidenced by an IGF-1 SD score of < –2.0 for age and gender at Visit 1, using provided normal data; or as the average of the IGF-1 SD score at Visit 1 and the most recent prior IGF-1 SD score from an approved IGF-1 assay.
- Short stature as defined by a height SD score of < –2.0 for age and gender using provided normal data
- Chronological age equals or more than 3 years and chronological or bone age equals or less than 11 in girls and equals or less than 12 in boys (if bone age alone was used, the bone age must have been taken within 6 months of screening)
- GH sufficiency, defined at Visit 2 as a maximal arginine-clonidine stimulated GH response of equials or more than 7 ng/mL (or with other stimulants approved by the Sponsor).
- Prepubertal Status: Girls were at less than Tanner stage 2 breast development and boys had testicular volume equials or more than 3 mL, as measured by the standardized orchidometer (Prader type). The onset of pubic hair development, up to and including Tanner stage 2, was allowed at study entry.
- Adequate nutrition as evidenced by a body mass index greater than or equal to the 5th percentile for age and gender using provided normal data |
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E.4 | Principal exclusion criteria |
- Documented mutation of the GH receptor (Laron syndrome) or documented deletion of the GH gene
- Any previous therapeutic use of IGF-1, GH, Lupron®, or sex steroids. A short-term (i.e., 7 days or fewer) exposure to GH for a diagnostic test was permitted.
- Known or suspected allergy to trial product or related products
- Chronic illness, including diabetes mellitus, inborn errors of metabolism, osteo- or chondrodystrophies, disease of the genitourinary, cardiopulmonary,
gastrointestinal, or central nervous system.
- Chromosomal aneuploidy (eg, Down syndrome, trisomies, Turner syndrome, etc.)
- Syndromes with known predisposition to develop malignant tumors (eg, Bloom syndrome, Fanconi syndrome)
- Prior bone marrow transplantation
- Any named syndrome known associated with short stature, including but not
limited to Prader-Willi syndrome, Russell-Silver syndrome, Turner syndrome, and Noonan syndrome
- Active seizure disorders, defined as one or more seizures per month, irrespective of anticonvulsant therapy
- Administration of any growth-altering medication within 3 months of Visit 1
- Significant abnormality in clinical screening laboratories, as determined by the investigator
- Any current or previous exposure to therapeutic spinal irradiation
- Evidence of clinical malnutrition or growth deficit attributable to emotional deprivation
- Evidence of any active malignancy or intracranial tumors
- Use of investigational medication(s) within the last month
- Any other 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) |
First-year height velocity |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline (Visit 4) to 12 months (Visit 9) |
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E.5.2 | Secondary end point(s) |
Change in height SD score, bone age, changes in serum concentrations of IGF-1, IGF-2, insulin-like growth factor binding protein-2 (IGFBP-2), and insulin-like growth factor binding protein-3 (IGFBP-3) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline (Visit 4) to 12 months (Visit 9) |
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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 | Yes |
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 |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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.8.9.2 | In all countries concerned by the trial years | 1 |