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Optimization of the Dosage Regimen of Growth Hormone Therapy in Children Born Small for Gestational Age (SGA OPTIMIS)

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ClinicalTrials.gov Identifier: NCT00249821
Recruitment Status : Completed
First Posted : November 7, 2005
Results First Posted : October 10, 2012
Last Update Posted : September 26, 2017
Sponsor:
Collaborator:
Merck Serono S.A.S., an affiliate of Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Small Gestational Age (SGA)
Intervention Drug: Saizen®
Enrollment 22
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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. 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.
Period Title: Overall Study
Started 10 12
Completed 10 11
Not Completed 0 1
Reason Not Completed
Technical problem             0             1
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day Total
Hide Arm/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. 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. Total of all reporting groups
Overall Number of Baseline Participants 10 12 22
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 12 participants 22 participants
8.00  (1.49) 7.90  (0.90) 8.00  (1.17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 12 participants 22 participants
Female
4
  40.0%
4
  33.3%
8
  36.4%
Male
6
  60.0%
8
  66.7%
14
  63.6%
1.Primary Outcome
Title Height Velocity
Hide 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.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis (FA) set included all the participants 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.
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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.
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.
Overall Number of Participants Analyzed 10 12
Mean (Standard Deviation)
Unit of Measure: centimeter (cm)/year
6.40  (1.35) 4.40  (1.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Month 12: Analysis of co-variance (ANCOVA) method with covariates “height” and “age” at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Height-Standard Deviation Score (H-SDS) at Month 6 and Month 12
Hide 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.
Time Frame Baseline (randomization), Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all the participants 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.
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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.
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.
Overall Number of Participants Analyzed 10 12
Mean (Standard Deviation)
Unit of Measure: standard deviation score
Baseline (randomization) -1.30  (0.42) -1.50  (0.37)
Change at Month 6 0.30  (0.22) 0.10  (0.10)
Change at Month 12 0.30  (0.30) -0.10  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Change at Month 6: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Change at Month 12: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Height Velocity-Standard Deviation Score (HV-SDS)
Hide 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.
Time Frame Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all the participants who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. Here "n" signifies number of participants analyzed at that particular time point for each arm group respectively. LOCF was used to impute missing values.
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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.
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.
Overall Number of Participants Analyzed 10 12
Mean (Standard Deviation)
Unit of Measure: standard deviation score
Month 6 (n= 10,11) 0.60  (0.44) 0.10  (0.22)
Month 12 (n=10,12) 0.30  (0.29) -0.10  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Month 6: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Month 12: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Height at Month 6
Hide Description [Not Specified]
Time Frame Baseline (randomization) and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all the participants 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.
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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.
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.
Overall Number of Participants Analyzed 10 12
Mean (Standard Deviation)
Unit of Measure: cm
Baseline (randomization) 121.10  (7.99) 119.20  (5.29)
Change at Month 6 3.60  (1.31) 2.50  (0.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Change at Month 6: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Bone Age at Month 12
Hide Description Bone age was assessed by a left wrist X-Ray and evaluated by the investigator according to the Greulich and Pyle method.
Time Frame Baseline (randomization) and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
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 participants analyzed) signified those participants who were evaluable for this measure and "n" = number of participants analyzed at that particular time point for each arm group respectively.
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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.
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.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: years
Baseline (randomization) (n = 9,10) 7.50  (0.82) 7.00  (1.85)
Change at Month 12 (n=9,7) 1.40  (0.79) 1.40  (0.89)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Change at Month 12: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.972
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
6.Secondary Outcome
Title Insulin Like Growth Factor-1 (IGF-1) Levels
Hide Description [Not Specified]
Time Frame Baseline (randomization), Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
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 participants analyzed) signified those participants who were evaluable for this measure and "n" = number of participants analyzed at that particular time point for each arm group respectively.
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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.
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.
Overall Number of Participants Analyzed 10 11
Mean (Standard Deviation)
Unit of Measure: microgram/liter (mcg/L)
Baseline (randomization) (n= 10,11) 319.60  (146.27) 275.40  (98.82)
Month 6 (n= 9,7) 369.30  (120.13) 262.40  (65.52)
Month 12 (n=10,10) 414.30  (176.70) 263.00  (120.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Month 6: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Month 12: ANCOVA method with covariates “height” and “age” at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Hide Description [Not Specified]
Time Frame Baseline (randomization), Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
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 participants analyzed) signified those participants who were evaluable for this measure and "n" = number of participants analyzed at that particular time point for each arm group respectively.
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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.
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.
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: milligram/L (mg/L)
Baseline (randomization) (n= 10,10) 3.40  (0.70) 3.40  (0.60)
Month 6 (n= 9,7) 3.00  (0.84) 3.30  (0.81)
Month 12 (n= 9,10) 3.60  (1.02) 3.50  (0.77)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Month 6: ANCOVA method with covariates "height" and "age" at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.793
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Saizen® 0.057 mg/kg/Day, Saizen® 0.035 mg/kg/Day
Comments Month 12: ANCOVA method with covariates "height" and "age" at baseline was used to calculate presented p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.055
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide 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).
Time Frame Baseline (randomization) until Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all the participants who received at least 1 dose of study medication.
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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.
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.
Overall Number of Participants Analyzed 10 12
Measure Type: Number
Unit of Measure: participants
2 1
Time Frame 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.
Adverse Event Reporting 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 participants who completed the study.
 
Arm/Group Title Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Hide Arm/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. 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.
All-Cause Mortality
Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/12 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Saizen® 0.057 mg/kg/Day Saizen® 0.035 mg/kg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/10 (20.00%)      1/12 (8.33%)    
Immune system disorders     
Asthma * 1  0/10 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations     
Bronchitis * 1  1/10 (10.00%)  1 0/12 (0.00%)  0
Ear infection * 1  1/10 (10.00%)  2 0/12 (0.00%)  0
Investigations     
Insulin-like growth factor increased * 1  1/10 (10.00%)  1 0/12 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Participants’ inclusion period was extended but due to remaining low recruitment rate, it was finally decided to stop enrollment even if only 22 participants were enrolled.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT00249821     History of Changes
Other Study ID Numbers: IMP 25735
First Submitted: November 4, 2005
First Posted: November 7, 2005
Results First Submitted: June 28, 2012
Results First Posted: October 10, 2012
Last Update Posted: September 26, 2017