E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Extreme short stature that does not have a diagnostic explanation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066333 |
E.1.2 | Term | Idiopathic short stature |
E.1.2 | System Organ Class | 100000004859 |
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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 evaluate the efficacy of recombinant human growth hormone (hGH) (Norditropin® Nordilet®) therapy compared with untreated group assessed by height velocity after 6 months of treatment in patients with idiopathic short stature (ISS) in Korea |
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E.2.2 | Secondary objectives of the trial |
- Evaluate height standard deviation scores in treatment (trt) group compared with untreated group after 6 months of trt - Evaluate concentrations of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in trt group compared with untreated group after 6 months of trt - Evaluate the safety profile of trt group as assessed by adverse events (AEs), physical examination, vital signs, clin. laboratory tests and bone age compared with untreated group after 6 months of trt - Evaluate the safety profile of group A (12-month GH trt period) as assessed by AEs, physical examination, vital signs, clin. laboratory tests and bone age during the trial - Evaluate the safety profile of group B (6-month untreated period followed by 6-month GH trt period) as assessed by AEs, physical examination, vital signs, clin. laboratory tests and bone age during the last 6-month trt period - Compare Ht-V of the first 6-month trt period with the following 6-month trt period in group A
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Informed consent obtained from subject’s parents or legally acceptable representative before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.) · Pre-pubertal status (males aged from 4 to 11 [both inclusive], females aged from 4 to 9 [both inclusive]): an absence of breast development in females (Tanner 1 only) and testicular volume < 4 mL in males · Height below 3 percentile† · Epiphyses confirmed as open in patients ≥10 years of age · Growth hormone level above 10 ng/mL following a stimulation test (test result within 6 months from screening can be used) · Bone age ≤ 12 years †:According to the 2007 Korean National growth chart (see Appendix D) |
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E.4 | Principal exclusion criteria |
· Known presence of one or more pituitary hormone deficiencies (ACTH, ADH, FSH, LH, TSH) · Known primary hypothyroidism, adrenal insufficiency or hypogonadism (treated or untreated) · Specific types of growth failure including, but not limited to, known chromosomal abnormalities associated with growth failure and altered sensitivity to growth hormone · Bone age is advanced over chronological age more than 3 years (inclusive) · Active malignancy, CNS trauma, active chemotherapy or radiation therapy for neoplasia within 5 years prior to screening (Visit 1) · Prior history of intracranial hypertension · Hypertrophic cardiomyopathy |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 6 months of treatment
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E.5.2 | Secondary end point(s) |
1 Change in the following parameters a - Ht-SDS b - IGF related factors: IGF-I c - IGF related factors: IGFBP-3 2 - Ht-V 3 - Occurrence of Adverse events 4 - Change in bone age |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1a, 1b, 1c - From the baseline to 6-month treatment 2 - At the first 6 months and the last 6 months of group A 3 - Throughout the trial (12 months) 4 - From baseline to 6-month treatment and 12-month treatment, respectively. In addition, for group B: From 6 months to 12 months
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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) | 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 |
Compare 12 months of treatment with 6 months of no treatment followed by 6 months treatment |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |