Clinical Trial Results:
Optimization of the dosage regimen with growth hormone therapy in children born small for gestational age. An open label, randomized pilot study, comparing in children treated for 3 years, the efficacy of a Saizen® treatment at the same dose versus a lower maintenance dose prolonged during 1 additional year (SGA OPTIMIS)
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Summary
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EudraCT number |
2015-001696-51 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
12 Sep 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
23 May 2016
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First version publication date |
05 Aug 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
25735
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00249821 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck KGaA
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Sponsor organisation address |
Frankfurter Strasse 250, Darmstadt, Germany, 64293
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Public contact |
Communication Centre merck KGaA, Merck KGaA, +49 6151725200, service@merckgroup.com
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Scientific contact |
Communication Centre Merck KGaA, Merck KGaA, +49 6151725200, service@merckgroup.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Sep 2007
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Sep 2007
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Sep 2007
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluating the benefit in terms of height gain of a fourth year of an recombinant human growth hormone (r-hGH) induction regimen with a daily dose of 0.057 milligram /kilogram/day (mg/kg/day) in comparison to a maintenance regimen at a lower daily dose of 0.035 mg/kg/day, after an initial 3-year period at the induction dose of 0.057mg/kg/day in subjects born Small for gestational age (SGA).
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Protection of trial subjects |
Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Feb 2005
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 22
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Worldwide total number of subjects |
22
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EEA total number of subjects |
22
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
22
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
First subject signed informed consent form: February 28, 2005. Clinical data cutoff: September 12, 2007, Study completion date: September 12, 2007. | |||||||||||||||
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Pre-assignment
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Screening details |
A total of 22 subjects were included in the trial. | |||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Saizen® 0.035 mg/kg/day | |||||||||||||||
Arm description |
Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Somatropin
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Investigational medicinal product code |
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Other name |
Saizen
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
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Arm title
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Saizen® 0.057 mg/kg/day | |||||||||||||||
Arm description |
Saizen® r-hGH subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Somatropin
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Investigational medicinal product code |
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Other name |
Saizen
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.
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Baseline characteristics reporting groups
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Reporting group title |
Saizen® 0.057 mg/kg/day
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Reporting group description |
Saizen® r-hGH subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Saizen® 0.035 mg/kg/day
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Reporting group description |
Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Saizen® 0.035 mg/kg/day
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Reporting group description |
Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months. | ||
Reporting group title |
Saizen® 0.057 mg/kg/day
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Reporting group description |
Saizen® r-hGH subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months. | ||
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End point title |
Height Velocity | ||||||||||||
End point description |
Height Velocity (HV) is the change in height since the previous year´s measurement and more precisely:
HV = {(h-hp)/(d-dp)} * 365.25 [centimeter (cm)/year] where h is current height in cm, hp is previous height in cm, closest to 1 year previous, d is the current date and dp is the date of measurement of previous height, closest to 1 year previous. Additionally, d and dp have to be within 0.6 years and 1.5 years. HV is the mean height velocity over the interval between d and dp but is displayed as HV at d. Full Analysis (FA) set included all the subjects who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. Last observation carried forward (LOCF) was used to impute missing values.
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End point type |
Primary
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End point timeframe |
Month 12
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Statistical analysis title |
Statistical Analysis for Height Velocity | ||||||||||||
Statistical analysis description |
Month 12: Analysis of co-variance (ANCOVA) method with covariates “height” and “age” at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
22
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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End point title |
Change from baseline in Height-Standard Deviation Score (H-SDS) at Month 6 and Month 12 | |||||||||||||||||||||
End point description |
Height-Standard Deviation Score (H-SDS) was calculated as height minus mean (age-and sex-matched reference) divided by standard deviation (SD) [age and sex-matched reference]. Greater H-SDS indicates greater height. FA set included all the subjects who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. LOCF was used to impute missing values.
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End point type |
Secondary
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End point timeframe |
Baseline (randomization), Month 6 and Month 12
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Statistical analysis title |
Statistical analysis H-SDS: Month 6 | |||||||||||||||||||||
Statistical analysis description |
Change at Month 6: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
22
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
= 0.012 | |||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||
Confidence interval |
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Statistical analysis title |
Statistical analysis H-SDS: Month 12 | |||||||||||||||||||||
Statistical analysis description |
Change at Month 12: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
22
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
= 0.002 | |||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||
Confidence interval |
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End point title |
Height velocity-Standard deviation score (HV-SDS) | ||||||||||||||||||
End point description |
Height Velocity-Standard Deviation Score (HV-SDS) was calculated as height velocity minus reference mean height velocity divided by SD of the reference mean height velocity. Greater HV-SDS indicates greater height velocity. FA set included all the subjects who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. Here "n" signifies number of subjects analyzed at that particular time point for each arm group respectively. LOCF was used to impute missing values.
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End point type |
Secondary
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End point timeframe |
Month 6 and Month 12
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Statistical analysis title |
Statistical analysis HV-SDS: Month 6 | ||||||||||||||||||
Statistical analysis description |
Month 6: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
22
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.022 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Confidence interval |
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Statistical analysis title |
Statistical analysis HV-SDS: Month 12 | ||||||||||||||||||
Statistical analysis description |
Month 12: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
22
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.002 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Confidence interval |
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End point title |
Change from baseline in height at Month 6 | ||||||||||||||||||
End point description |
FA set included all the subjects who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. LOCF was used to impute missing values.
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End point type |
Secondary
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End point timeframe |
Baseline (randomization) and Month 6
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Statistical analysis title |
Statistical Analysis:change from baseline height | ||||||||||||||||||
Statistical analysis description |
Change at Month 6: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
22
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.029 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Confidence interval |
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End point title |
Change from baseline in bone age at Month 12 | ||||||||||||||||||
End point description |
Bone age was assessed by a left wrist X-Ray and evaluated by the investigator according to the Greulich and Pyle method.FA set included all participants who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. ‘N’ (Number of subjects analyzed) signified those participants who were evaluable for this measure and "n" = number of subjects analyzed at that particular time point for each arm group respectively.
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End point type |
Secondary
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End point timeframe |
Baseline (randomization) and Month 12
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Statistical analysis title |
Statistical Analysis:change from baseline: height | ||||||||||||||||||
Statistical analysis description |
Change at Month 12: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
19
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.972 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Confidence interval |
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End point title |
Insulin Like Growth Factor-1 (IGF-1) Levels | |||||||||||||||||||||
End point description |
FA set included all subjects who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. ‘N’ (Number of subjects analyzed) signified those participants who were evaluable for this measure and "n" = number of subjects analyzed at that particular time point for each arm group respectively.
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End point type |
Secondary
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End point timeframe |
Baseline (randomization), Month 6 and Month 12
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Statistical analysis title |
Statistical Analysis:IGF-1 Month 6 | |||||||||||||||||||||
Statistical analysis description |
Month 6: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
= 0.058 | |||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||
Confidence interval |
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level |
95% | |||||||||||||||||||||
Statistical analysis title |
Statistical Analysis:IGF-1 Month 12 | |||||||||||||||||||||
Statistical analysis description |
Month 12: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
= 0.026 | |||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||
Confidence interval |
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End point title |
Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Levels | |||||||||||||||||||||
End point description |
FA set included all subjects who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. ‘N’ (Number of subjects analyzed) signified those subjects who were evaluable for this measure and "n" = number of subjects analyzed at that particular time point for each arm group respectively.
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End point type |
Secondary
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End point timeframe |
Baseline (randomization), Month 6 and Month 12
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Statistical analysis title |
Statistical Analysis:IGBP-3: Month 6 | |||||||||||||||||||||
Statistical analysis description |
Month 6: ANCOVA method with covariates "height" and "age" at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
= 0.793 | |||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||
Confidence interval |
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Statistical analysis title |
Statistical Analysis:IGBP-3: Month 12 | |||||||||||||||||||||
Statistical analysis description |
Month 12: ANCOVA method with covariates "height" and "age" at baseline was used to calculate presented p-value.
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Comparison groups |
Saizen® 0.057 mg/kg/day v Saizen® 0.035 mg/kg/day
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
= 0.055 | |||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||
Confidence interval |
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End point title |
Number of subjectss with treatment emergent adverse events (TEAEs) | ||||||||||||
End point description |
Adverse Events (AEs): Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications. TEAEs: AEs that occur during treatment with the Investigational Medicinal Product (IMP). The safety population included all the subjects who received at least 1 dose of study medication.
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End point type |
Secondary
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End point timeframe |
Baseline (randomization) until Month 12
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Events (AEs) are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until 4 weeks post drug administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment.
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Adverse event reporting additional description |
Pre-Treatment:Medical conditions present at initial study visit that did not worsen in severity or frequency during study;Treatment-Emergent: If onset date of AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of AE was post 4 weeks after drug administration for subjects who completed the study.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.0
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Reporting groups
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Reporting group title |
Saizen® 0.035 mg/kg/day
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Reporting group description |
Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Saizen® 0.057 mg/kg/day
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Reporting group description |
Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Subject's inclusion period was extended but due to remaining low recruitment rate, it was finally decided to stop enrollment even if only 22 subjects were enrolled. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/22508151 |
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