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
Condition: Hypochondroplasia
MeSH terms: Dwarfism; Lordosis; Limb Deformities, Congenital
Intervention: Recombinant human growth hormone (r-hGH)
Intervention description: Subjects will receive a single subcutaneous injection of recombinant human growth hormone (r-hGH) equivalent to a dose of 0.057 milligram per kilogram per day (mg/kg/day). The dose will be subsequently adjusted during the trial and subjects will be treated for at least 3 years or until near final height is reached.
Intervention MeSH terms: Hormones
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 3 Years
Healthy volunteers: No
Keywords: Hypochondroplasia; Skeletal dysplasia; Growth; Growth Hormone; Recombinant-human Growth Hormone

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