Clinical trial NCT01111019: Efficacy and Safety Evaluation of Recombinant Human Growth Hormone (r-hGH), Saizen®, on a Population of Children With Hypochondroplasia, Treated at Least 3 Years or Until Near Final Height, When Applicable, in Comparison With a Historic Cohort of Non-treated Children
Official title: Efficacy and Safety Evaluation of Recombinant Human Growth Hormone (r-hGH), Saizen®, on a Population of Children With Hypochondroplasia, Treated Over a Period of 3 Years or 5 Years if Applicable, in Comparison With a Historic Cohort of Non-treated Children With Hypochondroplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypochondroplasia
Keywords: Hypochondroplasia
Skeletal dysplasia
Growth
Growth Hormone
Recombinant-human Growth Hormone
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Merck Serono S.A.S, France
First posted: 2010-04-27
Enrollment: 19
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is conducted to describe the efficacy and safety of recombinant human growth hormone (r-hGH) treatment Saizen® on children with hypochondroplasia.


Eligibility criteria: Inclusion Criteria:

* Male or female children with hypochondroplasia defined by a disproportional short limb height and a X-ray evidence of shortening of the long bones and failure of increase in the interpedicular distance between lumbar vertebrae L1 and L5
* Result of genetic analysis for mutation of gene FGFR3 already known or ongoing analysis at the beginning of the study
* Chronological age greater than or equal to 3 years
* Height for chronological age less than or equal to - 2 SDS
* Bone age less than or equal to 11 years for girls and 13 years for boys
* A written informed consent at the beginning of the pre-treatment period must be obtained from the parent(s)/legal guardian(s). Children able to understand the trial should personally sign and date the written informed consent

Additional inclusion criteria for each study prolongation:

* Bone age at Month 36 or Month 60 is compatible with treatment prolongation according to investigator opinion
* Subject is still under r-hGH treatment with Saizen® at Month 36 or Month 60
* Height gain greater than or equal to + 1 SDS after the 2 first years of treatment for treatment prolongation at Month 36 and growth velocity greater than or equal to 5 centimeter (cm) per year, with bone age less than 14 years for females or less than 16 years for males for treatment prolongation at Month 60
* According to investigator opinion, gene mutations of the subjects are not in connection with observed side effects during the 3 or 5 first years of treatment
* An updated written informed consent must be obtained from the parent(s)/legal guardian(s) before the start of each study prolongation. Children able to understand the trial should personally sign and date the written informed consent

Exclusion Criteria:

* Turner's Syndrome in girls
* Active malignant neoplastic disease
* Severe congenital malformations
* Proliferative or preproliferative diabetic retinopathy
* Evidence of any progression or recurrence of an underlying intra-cranial space occupying lesion
* Severe psychomotor retardation
* Diabetes mellitus or history of significant glucose intolerance as defined by a fasting blood glucose greater than 6.4 millimole per liter (mmol/L)
* Known renal insufficiency as defined by serum creatinine level 1.0 milligram per deciliter (mg/dL) (88 micromole per liter \[mcmol/L\])
* Known hepatic disease as defined by elevated liver enzymes or total bilirubin (\* 2 Normal)
* Current congestive heart failure, untreated hypertension, serious chronic edema of any cause
* Chronic infectious disease
* History of intracranial hypertension with papilledema
* Previous or ongoing treatment with sex steroid therapy such as estrogens or testosterone
* Previous or ongoing treatment with any therapy that may directly influence growth, including Growth Hormone (GH), Growth Hormone Releasing Hormone (GHRH) and long duration corticosteroids therapy
* Known hypersensitivity to somatropin or any of the excipients
* Epiphyseal fusion
* Participation to any clinical study within the 30 days preceding study entry
* Pregnant females

Primary outcomes:
measure: Change From Baseline in Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects at Year 3
timeFrame: Baseline (Month 0), Year 3
measure: Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects at Year 4
timeFrame: Year 4
Secondary outcomes:
measure: Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects
timeFrame: Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)
measure: Change From Baseline in Height of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years
timeFrame: Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)
measure: Change From Baseline in Upper Segment (Superior) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years
timeFrame: Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)
measure: Change From Baseline in Weight of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years
timeFrame: Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)
measure: Change From Baseline in Body Mass Index (BMI) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years
timeFrame: Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)
measure: Change From Baseline in Bone Mineral Density (BMD) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9 Years
timeFrame: Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 9 (only for male)
measure: Change From Baseline in Percent Body Fat Mass of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9 Years
timeFrame: Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 9 (only for male)
measure: Change From Baseline in Lean Body Mass (LBM) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9 Years
timeFrame: Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 9 (only for male)
measure: Growth (Height) Velocity of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years
timeFrame: Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)
measure: Head Circumference Values of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years
timeFrame: Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)
measure: Osteocalcin Values of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years
timeFrame: Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male), 9.5 (only for male)
measure: C-terminal Telopeptide (CTX) Values of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years
timeFrame: Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male), 9.5 (only for male)
measure: Number of Subjects With Fibroblast Growth Factor Receptor (FGFR3) Mutation
timeFrame: Baseline up to 3 years
measure: Number of Subjects With Adverse Event (AE) and Serious Adverse Event (SAE)
timeFrame: Baseline up to 9.5 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Endocrinologie Pédiatrique - centre des maladies rares de la croissance -Hôpital Necker Enfants Malades
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Pinto G, Cormier-Daire V, Le Merrer M, Samara-Boustani D, Baujat G, Fresneau L, Viaud M, Souberbielle JC, Pineau JC, Polak M. Efficacy and safety of growth hormone treatment in children with hypochondroplasia: comparison with an historical cohort. Horm Res Paediatr. 2014;82(6):355-63. doi: 10.1159/000364807. Epub 2014 Oct 15.