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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck Serono S.A.S, France
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01111019
First received: April 23, 2010
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Hypochondroplasia
Drug: Recombinant human growth hormone (Somatropin)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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 With Hypochondroplasia

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Height-Standard deviation score (SDS) of treated children with hypochondroplasia over recombinant human growth hormone (r-hGH) treatment duration [ Time Frame: 3 years to 5 years or until near final height is reached, (if applicable) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Growth velocity (SDS/year) of treated children with hypochondroplasia over r-hGH treatment duration [ Time Frame: 3 years to 5 years or until near final height is reached, (if applicable) ] [ Designated as safety issue: No ]
  • Body proportions of treated children with hypochondroplasia over r-hGH treatment duration [ Time Frame: 3 years to 5 years or until near final height is reached, (if applicable) ] [ Designated as safety issue: No ]
    Body proportions include head circumference, superior segment, height, weight, and body mass index (BMI)

  • Genotype fibroblast growth factor receptor (FGFR3) of subjects [ Time Frame: 3 to 5 years (if applicable) ] [ Designated as safety issue: No ]
  • Body composition of treated children with hypochondroplasia over r-hGH treatment duration [ Time Frame: 3 years to 5 years or until near final height is reached, (if applicable) ] [ Designated as safety issue: No ]
    Body composition includes percent body fat, lean muscle mass, bone mineral density (BMD), osteocalcin, and carboxyterminal cross-linking (CTX)

  • Adverse event (AE) and serious adverse event (SAE) during the treatment and follow-up period [ Time Frame: years to 5 years or until near final height is reached, (if applicable) ] [ Designated as safety issue: Yes ]
    This includes local tolerance at the injection site, clinical tolerance at each visit and assessment of biological tolerance every 6 months.


Enrollment: 19
Study Start Date: March 2006
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treated subjects
Subjects will be treated with 0.057 milligram per kilogram per day (mg/kg/day) r-hGH. Subjects still under treatment after 31 January 2011 will be treated with a dose reduced to 0.035 mg/kg/day until the end of the study.
Drug: Recombinant human growth hormone (Somatropin)
Recombinant human growth hormone (Somatropin) will be administered at 0.057 mg/kg/day subcutaneous injection for 3 years, 5 years or until near final height is reached, if applicable. Subjects still under treatment after 31 January 2011 will be treated with a dose reduced to 0.035 mg/kg/day until the end of the study.
Other Name: Saizen®
No Intervention: Historic cohort of non-treated subjects

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111019

Locations
France
Endocrinologie Pédiatrique - centre des maladies rares de la croissance -Hôpital Necker Enfants Malades
Paris, France, 75015
Sponsors and Collaborators
Merck KGaA
Merck Serono S.A.S, France
Investigators
Principal Investigator: Michel Polak, MD, PhD Endocrinologie Pédiatrique & INSERM U845, centre des maladies rares de la croissance, Hôpital Necker Enfants Malades
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01111019     History of Changes
Other Study ID Numbers: IMP 26545 (EMR701048-506)
Study First Received: April 23, 2010
Last Updated: July 9, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Merck KGaA:
Hypochondroplasia
Skeletal dysplasia
Growth
Growth Hormone
Recombinant-human Growth Hormone

Additional relevant MeSH terms:
Dwarfism
Limb Deformities, Congenital
Lordosis
Bone Diseases
Bone Diseases, Developmental
Congenital Abnormalities
Endocrine System Diseases
Genetic Diseases, Inborn
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Spinal Curvatures
Spinal Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014