Trial record 3 of 4 for:    "Skeletal dysplasias"

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: September 7, 2012
Last verified: September 2012
  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 2013 (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
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: September 7, 2012
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:
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014