Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Saizen in Intra-uterine Growth Retardation

This study has been completed.
Sponsor:
Collaborator:
Merck Serono S.A., Geneva
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01400698
First received: July 21, 2011
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

Study of safety of Saizen® in children born with serious intra-uterine growth retardation (IUGR) treated to final height. An open, phase III study involving 17 centers in France.

The study enrolled children who have completed 3 or 2 years of treatment and at least one year of post treatment observation in the Sponsor Studies GF 4001 (Safety and Efficacy of Saizen in the Treatment of Young Children Born with Severe IUGR) or GF 6283 (Effect of Intermittent versus Continuous Saizen Therapy in Young Children Born with Severe IUGR), respectively.

Detailed description: Serious IUGR is a syndrome characterized by low birth length and weight for gestational age (less than 10 percentile). The secretion of growth hormone in response to provocative stimuli (e.g. arginine, insulin) is normal in these children. Apart from low birth weight, children born with IUGR may have minor or major malformations.

A catch-up period with a supraphysiological growth velocity generally occurs during the first 6 to 24 months of life in 80 to 90 percent (%) of these children. This generally allows them to reach normal height. That means that conversely, approximately 10 to 20% of children do maintain a statural handicap. Puberty occurs at a normal age and the retardation in bone maturation present during the first years of life disappears very quickly. This leads to short adult stature in subjects who have not shown spontaneous catch-up during the first years of life. A safe and effective means of promoting growth without accelerating the timing or tempo of puberty would therefore be desirable.


Condition Intervention Phase
Children Born With Serious Intra-uterine Growth Retardation
Drug: Saizen® A
Drug: Saizen® B
Other: Observation only
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Study of the Safety and Efficacy of Saizen®, (Recombinant Human Growth Hormone, r-hGH), in Children Born With Serious Intra-uterine Growth Retardation (IUGR) Treated to Final Height

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Final Height [ Time Frame: One year after final height was attained up to 10.6 years ] [ Designated as safety issue: No ]
    Final height was defined as the height reached 1 year after height velocity (HV) was less than 2 centimeter/year (cm/year). Height velocity was the change in height since the previous year's measurement. Height was measured with a wall-mounted stadiometer (or in supine position if the participant's age was less than 3 years) and the measurement was repeated thrice by the same observer. The mean of the values obtained in the repeated measurements was taken for the analysis.

  • Height Standard Deviation Score (HSDS) [ Time Frame: One year after final height was attained up to 10.6 years ] [ Designated as safety issue: No ]
    HSDS was calculated as height minus reference mean height divided by SD of the reference mean height, both given by the reference growth table (Sempe) for the corresponding chronological age at the height measurement. Greater HSDS indicate greater height. (Sempe M et al., 1979)


Secondary Outcome Measures:
  • Parental Adjusted Height Standard Deviation Score (PAHSDS) [ Time Frame: One year after final height was attained up to 10.6 years ] [ Designated as safety issue: No ]
    PAHSDS is the distance between the participant's current and target heights, expressed in units of SD of the height distribution of the reference population. Target height is a measure of the height which the participant could hypothetically reach based only on his parents' heights. Target height standard deviation score (THSDS) was calculated as target height minus mean adult height of the reference population divided by SD of the mean adult height of the reference population.


Enrollment: 91
Study Start Date: November 1998
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Saizen® (Continuous or intermittent treatment) Drug: Saizen® A
Continuous or intermittent treatment with recombinant human Growth Hormone (r-hGH) 0.067 milligram/kilogram/day (mg/kg/day) subcutaneously (sc).
Other Names:
  • r-hGH
  • Somatropin
Experimental: Saizen® (Observed and then continuous or no treatment) Drug: Saizen® B
Observed until the first signs of puberty and then continuous treatment with r-hGH 0.067 mg/kg/day sc or observed without treatment.
Other Names:
  • r-hGH
  • Somatropin
Observation only Other: Observation only
Subjects were only observed.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previous inclusion, good compliance and normal completion of GF4001 or GF6283 in the treatment of growth failure in children born with serious IUGR (3-year continuous r-hGH treatment in GF4001 or 2-year continuous or intermittent r-hGH treatment in GF6283).
  • Increase in height greater than 0.5 standard deviation (SD) during the first 2 years of r-hGH treatment in GF4001 or after 2 years of continuous or intermittent r-hGH treatment in GF6283.
  • A written Informed Consent at the beginning of the pre-study visit must be obtained from the parent(s)/legal guardian(s), with the understanding that consent may be withdrawn by the subject or parents at any time without prejudice to their future medical care. Children able to understand the trial should personally sign and date the written informed consent, too.
  • Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

  • Known multiple malformation syndrome with severe psychomotor retardation and/or body hemihypertrophy.
  • Severe psychomotor retardation.
  • Severe congenital malformations.
  • Other protocol-defined exclusion criteria may apply.
  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: NCT01400698

Sponsors and Collaborators
Merck KGaA
Merck Serono S.A., Geneva
Investigators
Study Director: Medical Director Merck Serono S.A., Geneva
  More Information

Publications:
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01400698     History of Changes
Other Study ID Numbers: 20184
Study First Received: July 21, 2011
Results First Received: June 27, 2012
Last Updated: September 9, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee

Keywords provided by Merck KGaA:
Intra-uterine growth retardation (IUGR)
Saizen
Recombinant human growth hormone (r-hGH)
Final height
Bone age
SGA (Small for Gestational Age)

Additional relevant MeSH terms:
Fetal Growth Retardation
Fetal Diseases
Growth Disorders
Pathologic Processes
Pregnancy Complications
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014