E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Noonan syndrome associated short stature |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029748 |
|
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 is to evaluate the effect of Norditropin® on final height in children with Noonan syndrome |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
The present inclusion criteria are • Informed consent before any trial related activities • Participation in the original Norditropin® study (S/GHD/004/NOO) or following the protocol for S/GHD/004/NOO without being randomised in the trial The original inclusion criteria were • Verbal informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.) • Children with Noonan Syndrome. The diagnostic criteria will be
o Short stature o Hypertelorism o Low set ears o And one of the following criteria: Ptosis Cubiti valga Testicular dysplasia Hypogonadotroph hypogonadism • Bone age determination showing no significant acceleration (more than one year above chronological age) according to Greulich and Pyle (14). Patients showing an accelerated bone age (> chronological age) at the first examination will be reevaluated within 6 weeks before treatment start in order to evaluate the development process • Age at start of the treatment Age: 3.00-11.99 years • Prepubertal according to Tanner standards: < stage 2 with testes < 4 ml (boys) and no breast development (girls) • Height < -2 SD of the used Swedish National growth standards (15)taranger • Height velocity below 1 SD during the 12 months pre-treatment period (15) • Normal thyroid function • Normal karyotype • Available height data since birth • Parent heights available |
|
E.4 | Principal exclusion criteria |
The original exclusion criteria were • Earlier or ongoing treatment with growth hormone, anabolic steroids or corticosteroids • Subjects with congenital heart defect perceived to possibly have a major impact on growth • History of or actual endocrine, metabolic or other serious chronic disease perceived to possibly have a major impact on growth • Fasting blood glucose consistently above 6.7 mmol/l • Growth hormone deficiency defined as o GH levels below 10 µg/l during two consecutive GH stimulation tests
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint: Change in height SDS from start of treatment to final height (referenced to normal population)
Secondary Endpoints: Efficacy • Final height SDS (referenced to normal population and Noonan population, respectively) • Change in height SDS from start of treatment to final height (referenced to Noonan population) • Height velocity • Change in height velocity from start of treatment • Sitting height • Number and proportion of subjects with final height SDS above -2 SDS Safety • Adverse events (AEs) • HbA1c, Free Thyroxin and TSH • Fasting blood glucose and insulin • Haematology, serum biochemistry and urinalysis laboratory variables • Physical examinations, BP and pulse • Bone age • ECG • Echocardiography • IGF-I, and IGFBP-3 levels and SDS • PqCT for assessment of bone mineral status • DXA scan for assessment of body composition and bone mineral status • Plasma leptin, ghrelin and adiponectin for assessment of these growth hormone dependent hormones
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Present trial: Not randomised or controlled; Original trial as above. |
|
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 1 |