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Saizen in Intra-uterine Growth Retardation

Phase 3
Completed
Conditions
Children Born With Serious Intra-uterine Growth Retardation
Interventions
Other: Observation only
Registration Number
NCT01400698
Lead Sponsor
Merck KGaA, Darmstadt, Germany
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
91
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Saizen® (Continuous or intermittent treatment)Saizen® A-
Saizen® (Observed and then continuous or no treatment)Saizen® B-
Observation onlyObservation only-
Primary Outcome Measures
NameTimeMethod
Height Standard Deviation Score (HSDS)One year after final height was attained up to 10.6 years

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)

Final HeightOne year after final height was attained up to 10.6 years

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.

Secondary Outcome Measures
NameTimeMethod
Parental Adjusted Height Standard Deviation Score (PAHSDS)One year after final height was attained up to 10.6 years

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.

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