Saizen in Intra-uterine Growth Retardation
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.
|Children Born With Serious Intra-uterine Growth Retardation||Drug: Saizen® A Drug: Saizen® B Other: Observation only||Phase 3|
|Study Design:||Allocation: Randomized
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|
- Final Height [ Time Frame: One 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.
- Height Standard Deviation Score (HSDS) [ Time Frame: 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)
- Parental Adjusted Height Standard Deviation Score (PAHSDS) [ Time Frame: 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.
|Study Start Date:||November 1998|
|Study Completion Date:||February 2010|
|Primary Completion Date:||February 2010 (Final data collection date for primary outcome measure)|
|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).
|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: Observation only
Subjects were only observed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01400698
|Study Director:||Medical Director||Merck Serono S.A., Geneva|