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

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

Sponsors

Lead Sponsor: Merck KGaA, Darmstadt, Germany

Collaborator: Merck Serono S.A.S, France

Source Merck KGaA, Darmstadt, Germany
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.

Overall Status Completed
Start Date March 21, 2006
Completion Date January 17, 2017
Primary Completion Date January 17, 2017
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Change From Baseline in Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects at Year 3 Baseline (Month 0), Year 3
Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects at Year 4 Year 4
Secondary Outcome
Measure Time Frame
Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects 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)
Change From Baseline in Height of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years 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)
Change From Baseline in Upper Segment (Superior) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years 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)
Change From Baseline in Weight of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years 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)
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 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)
Change From Baseline in Bone Mineral Density (BMD) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9 Years Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 9 (only for male)
Change From Baseline in Percent Body Fat Mass of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9 Years Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 9 (only for male)
Change From Baseline in Lean Body Mass (LBM) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9 Years Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 9 (only for male)
Growth (Height) Velocity of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years 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)
Head Circumference Values of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years 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)
Osteocalcin Values of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years 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)
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 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)
Number of Subjects With Fibroblast Growth Factor Receptor (FGFR3) Mutation Baseline up to 3 years
Number of Subjects With Adverse Event (AE) and Serious Adverse Event (SAE) Baseline up to 9.5 years
Enrollment 19
Condition
Intervention

Intervention Type: Drug

Intervention Name: Recombinant human growth hormone (r-hGH)

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.

Arm Group Label: r-hGH (Saizen®)

Other Name: Saizen®, Somatropin

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

Gender: All

Minimum Age: 3 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Medical Responsible Study Director Merck KGaA, Darmstadt, Germany
Location
Facility: Endocrinologie Pédiatrique - centre des maladies rares de la croissance -Hôpital Necker Enfants Malades
Location Countries

France

Verification Date

October 2018

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: r-hGH (Saizen®)

Type: Experimental

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov