Children with Idiopathic Short Stature (ISS) at puberty onset. MedDRA version: 8.1 Level: LLT Classification code 10040600 Term: Short stature
Conditions
Interventions
Trade Name: ENANTONE® LP 11,25 mg
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Leuprorelin
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 11
Sponsors
LILLY FRANCE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female children with ISS defined as height = –2.5 SDS for age and gender (according to national references) or predicted adult height = –2.5 SDS at study entry based on the Bayley-Pinneau method, with a bone age reading by the central reader. 2.A chronological age = 8 years and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Growth hormone deficiency (GHD) based on two GH stimulation tests performed in the 3 years before the screening visit resulting in both GH values = 20 mIU/L (depending on the conversion factor, usually: 10 ng/ml). Note: one stimulation test with a GH peak value > 20 mIU/L (depending on the conversion factor, usually: 10 ng/ml) is sufficient to eliminate a GHD. 2.Chromosomal abnormality diagnosed locally on a karyotype. For girls, the karyotype, to eliminate a Turner syndrome, is mandatory. 3.Small for gestational age (SGA): defined as length and/or weight at birth < –2 SDS versus normal gestational age height and weight measurements (Usher and McLean standards). Patients will not be excluded due to an unknown birth weight or length. 4.Has reached menarche (had her first menstrual period). 7.Have been currently or previously treated with any drug that may directly influence growth, such as somatropin, growth hormone releasing hormone or GnRH agonists, anabolic steroids, or aromatase inhibitors. This includes the previous completion or withdrawal from this study or any other study investigating any of these treatments. 8.Have any significant concomitant disease that is likely to interfere with growth or with the study, or is a known contraindication to GH treatment (malignancy, intra-cranial tumor, chronic disease such as insulin-dependent diabetes mellitus, chronic infectious disease, chronic renal insufficiency, chronic heart failure, chronic hepatic disease, chronic pulmonary disease, active rheumatological disease, psychosis, neurofibromatosis, McCune Albright syndrome, dysmorphic syndromes such as Russell-Silver syndrome, Leri-Weill syndrome, achondroplasia, etc.) Hypothyroidism correctly substituted with thyroid hormone replacement treatment is not an exclusion criterion. 9.Have any known contraindication to GnRHa treatment (known hypersensitivity to GnRH, to GnRH agonists or to one of its ingredients) or presents genital bleeding of undetermined cause. 10.Receiving systemic or inhaled glucocorticoid therapy (more than ten days of treatment during the past three months) or receiving any other drug that is likely to directly interfere with growth (see classes of prohibited drugs in the appendix of protocol). A hypothyroidism correctly substituted with thyroid hormone replacement treatment is not an exclusion criterion. 11.Presenting with a lumbar spine BMD < –2 SDS (Z-score) assessed by DXA carried out at the screening visit and centrally assessed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is: To test the hypothesis that combined treatment with 0.05 mg/kg/day of somatropin (0.35 mg/kg/week) until adult height is reached and 11.25 mg of leuprorelin every three months for three years (or for a minimum two years and up to a chronological age of 13 years for girls and 15 years for boys, whichever occurs first) in pubertal children with idiopathic short stature results in a greater adult height, expressed in standard deviation score (SDS), than treatment with 0.05 mg/kg/day of somatropin alone (0.35 mg/kg/week) until adult height is reached. ;Secondary Objective: The secondary objectives of the study are : -To compare the annual height velocity, height SDS and gain in height velocity and height SDS between the two groups -To compare the difference between adult height SDS and target height SDS between the two groups. -To compare the difference between adult height SDS and baseline predicted height SDS between the two groups. -To compare the difference between adult height SDS and baseline height SDS between the two groups. -To compare the proportion of children with normal adult height SDS between the two groups. -To compare the annual progression of bone age between the two groups. -To compare the safety profiles between the two study groups. ;Primary end point(s): Gain in adult height SDS at last visit in patients with combined treatment (Humatrope and Enantone) compared to treatment with Humatrope alone. | — |
Countries
Netherlands
Outcome results
None listed