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Trial record 25 of 31 for:    IGFBP2

Prepubertal Children With Growth Failure Associated With Primary Insulin-Like Growth Factor-1 (IGF-1) Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00125164
Recruitment Status : Completed
First Posted : July 29, 2005
Results First Posted : April 30, 2010
Last Update Posted : June 21, 2012
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Growth Disorders
Insulin-Like Growth Factor-1 Deficiency
Intervention Drug: rhIGF-1 (mecasermin, Tercica, Inc.)
Enrollment 137
Recruitment Details Study Initiation Date: 14 March 2004. Study completion Date: 02 July 2008. 44 investigators screened subjects; 14 did not enroll any subjects. 137 subjects were enrolled. Consent for one randomized subject was withdrawn prior to any study measurements. This subject was excluded from all analyses.
Pre-assignment Details Subject screening consisted of three staged clinic visits over 6 weeks, including a medical history, complete physical examination, IGF-1 measurements, a Growth Hormone (GH) stimulation test, and an IGF-1 generation test.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description Observational Group Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm. Injection of rhIGF-1 80 μg/kg BID Injection of rhIGF-1 120 μg/kg BID
Period Title: Overall Study
Started 25 16 44 51
Completed 23 16 40 45
Not Completed 2 0 4 6
Reason Not Completed
Adverse Event             0             0             2             4
Lost to Follow-up             0             0             1             1
Withdrawal by Subject             2             0             1             1
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing) Total
Hide Arm/Group Description Observational Group Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm. Injection of rhIGF-1 80 μg/kg BID Injection of rhIGF-1 120 μg/kg BID Total of all reporting groups
Overall Number of Baseline Participants 25 16 44 51 136
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 16 participants 44 participants 51 participants 136 participants
7.0  (2.4) 7.6  (2.4) 7.7  (2.4) 7.6  (2.7) 7.5  (2.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 16 participants 44 participants 51 participants 136 participants
Female
10
  40.0%
4
  25.0%
14
  31.8%
8
  15.7%
36
  26.5%
Male
15
  60.0%
12
  75.0%
30
  68.2%
43
  84.3%
100
  73.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 16 participants 44 participants 51 participants 136 participants
Asian 1 0 1 2 4
Black 0 0 0 2 2
Hispanic 2 0 4 4 10
Native Hawaiian or Pacific Islander 0 0 0 1 1
White 22 16 38 41 117
Other 0 0 1 1 2
Stratum   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 16 participants 44 participants 51 participants 136 participants
Height Standard Deviation Score < -2.6 13 8 25 30 76
Height Standard Deviation Score >= -2.6 12 8 19 21 60
[1]
Measure Description: Please note that SD is a standard term used in growth studies and represents Standard Deviations calculated as the patient value minus the mean divided by the standard deviation. Standard Deviation Scores vary depending on the age and sex of the child.
Height Standard Deviation (SD) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  SD
Number Analyzed 25 participants 16 participants 44 participants 51 participants 136 participants
-2.8  (0.7) -2.6  (0.6) -2.7  (0.5) -2.9  (0.8) -2.8  (0.7)
[1]
Measure Description: Please note that SD is a standard term used in growth studies and represents Standard Deviations calculated as the patient value minus the mean divided by the standard deviation. Standard Deviation Scores vary depending on the age and sex of the child.
IGF-1 Standard Deviation (SD) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  SD
Number Analyzed 25 participants 16 participants 44 participants 51 participants 136 participants
-2.6  (0.7) -2.8  (0.8) -2.6  (0.7) -3.0  (0.8) -2.8  (0.8)
[1]
Measure Description: Please note that Standard Deviation (SD) Score is a term used in growth studies. The SD Score is calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child.
Maximum Stimulated Growth Hormone   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 25 participants 16 participants 44 participants 51 participants 136 participants
17.0  (6.5) 16.9  (6.2) 17.8  (9.0) 20.7  (16.8) 18.6  (12.1)
[1]
Measure Description: Growth Hormone Stimulation Test results expressed in ng/mL
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 25 participants 16 participants 44 participants 51 participants 136 participants
17.8  (4.6) 18.5  (4.7) 19.4  (5.4) 18.5  (5.7) 18.6  (5.3)
1.Primary Outcome
Title Height Velocity During the First Year - Intent to Treat (ITT)Population
Hide Description Height to be measured standing without shoes as the average of three measurements by the same observer using identical technique with a Harpenden or other wall mounted stadiometer. Reposition subject between each measurement.
Time Frame Measured at baseline and at one year
Hide Outcome Measure Data
Hide Analysis Population Description
A modified intention-to-treat population consisting of all randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with a baseline height measurement and at least one on-treatment height measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 22 0 42 49
Mean (Standard Deviation)
Unit of Measure: cm/yr
5.2  (1.0) 6.9  (1.0) 7.7  (1.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Untreated, 80 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The two-sided p-values for the comparisons are adjusted for multiple comparisons using Dunnett’s method.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.79
Confidence Interval 95%
1.19 to 2.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Untreated, 120 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The two-sided p-values for the comparisons are adjusted for multiple comparisons using Dunnett’s method.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.58
Confidence Interval 95%
1.99 to 3.16
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 80 μg/kg BID (Twice Daily Dosing), 120 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares the 80 and 120 µg/kg BID groups using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.79
Confidence Interval 95%
0.27 to 1.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Height Standard Deviation (SD) Score at One Year - ITT Population
Hide Description Height to be measured standing without shoes as the average of three measurements by the same observer using identical technique with a Harpenden or other wall mounted stadiometer. Reposition subject between each measurement. Please note that Standard Deviation (SD) Score is a term used in growth studies. The SD Score is calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child.
Time Frame Measured at baseline and at one year
Hide Outcome Measure Data
Hide Analysis Population Description
A modified intention-to-treat population that consists of all randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with a baseline height measurement and at least one on-treatment height measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 22 0 42 49
Mean (Standard Deviation)
Unit of Measure: SD/year
0.02  (0.24) 0.38  (0.17) 0.48  (0.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Untreated, 80 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The two-sided p-values for the comparisons are adjusted for multiple comparisons using Dunnett’s method.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.37
Confidence Interval 95%
0.24 to 0.50
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.07
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Untreated, 120 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The two-sided p-values for the comparisons are adjusted for multiple comparisons using Dunnett’s method.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.47
Confidence Interval 95%
0.34 to 0.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.06
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 80 μg/kg BID (Twice Daily Dosing), 120 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares the 80 and 120 µg/kg BID groups using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0495
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.11
Confidence Interval 95%
0.00 to 0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.05
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Changes in Bone Age From Baseline to One Year
Hide Description Plain X-rays of the left hand and wrist exposed for bone age appraisal. The films are sent to a central facility for standardized evaluation.
Time Frame Measured at baseline and at one year
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 23 0 40 44
Mean (Standard Deviation)
Unit of Measure: Year
0.8  (0.3) 1.1  (0.4) 1.2  (0.5)
4.Secondary Outcome
Title Percent Changes From Baseline in Serum Concentrations of IGF-1 at One Year
Hide Description Blood sample was collected while subject is in a fasting state for measuring the level of IGF-1 in the growth factor panel.
Time Frame Measured at baseline and at one year
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 18 0 34 42
Mean (Standard Deviation)
Unit of Measure: Percent change
64  (120) 227  (220) 266  (215)
5.Secondary Outcome
Title Percent Changes From Baseline in Serum Concentrations of IGF-2 at One Year
Hide Description Blood sample was collected for measuring the level of IGF-2 in the growth factor panel.
Time Frame Measured at baseline and at one year
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 17 0 35 40
Mean (Standard Deviation)
Unit of Measure: Percent change
14  (28) -38  (37) -37  (32)
6.Secondary Outcome
Title Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) at One Year
Time Frame Measured at baseline and at one year
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 15 0 32 34
Mean (Standard Deviation)
Unit of Measure: Percent change
-16  (26) 58  (84) 61  (79)
7.Secondary Outcome
Title Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) at One Year
Hide Description Blood sample was collected while subject is in a fasting state for measuring the level of IGFBP-3 in the growth factor panel.
Time Frame Measured at baseline and at one year
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with baseline measurement and Month 12 measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 18 0 34 42
Mean (Standard Deviation)
Unit of Measure: Percent change
13  (33) -19  (22) -19  (28)
8.Secondary Outcome
Title IGF Generation Test: Change of Serum IGF-1 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH)
Hide Description Blood drawn at Study Day 1, followed by 7 days of rhGH daily dosing at 0.05 mg/kg of body weight. Additional blood draw at Study Day 7.
Time Frame Study Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with measurements both pre and post exposure to rhGH. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 18 0 34 42
Mean (Standard Deviation)
Unit of Measure: ng/mL
40  (49) 53  (49) 48  (43)
9.Secondary Outcome
Title IGF Generation Test: Change of Serum IGFBP-3 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH)
Hide Description Blood drawn at Study Day 1, followed by 7 days of rhGH daily dosing at 0.05 mg/kg of body weight. Additional blood draw at Study Day 7.
Time Frame Study Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects in the untreated control, 80 and 120 µg/kg BID groups with measurements both pre and post exposure to rhGH. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 18 0 34 42
Mean (Standard Deviation)
Unit of Measure: mg/dL
744  (459) 800  (1095) 681  (568)
10.Post-Hoc Outcome
Title Height Velocity During the First Year for Subjects - Completers
Hide Description Height to be measured standing without shoes as the average of three measurements by the same observer using identical technique with a Harpenden or other wall mounted stadiometer. Reposition subject between each measurement.
Time Frame One Year
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects who completed 12 months of treatment in the untreated control, 80 and 120 µg/kg BID groups with a baseline height measurement and at least one on-treatment height measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 21 0 39 43
Mean (Standard Deviation)
Unit of Measure: cm/year
5.2  (1.0) 7.0  (1.0) 7.9  (1.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Untreated, 80 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The two-sided p-values for the comparisons are adjusted for multiple comparisons using Dunnett’s method.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.83
Confidence Interval 95%
1.26 to 2.40
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Untreated, 120 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The two-sided p-values for the comparisons are adjusted for multiple comparisons using Dunnett’s method.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.83
Confidence Interval 95%
2.26 to 3.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 80 μg/kg BID (Twice Daily Dosing), 120 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares the 80 and 120 µg/kg BID groups using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.01
Confidence Interval 95%
0.50 to 1.51
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.25
Estimation Comments [Not Specified]
11.Post-Hoc Outcome
Title Change From Baseline in Height Standard Deviation (SD) Score at One Year - Completers
Hide Description Height to be measured standing without shoes as the average of three measurements by the same observer using identical technique with a Harpenden or other wall mounted stadiometer. Reposition subject between each measurement. Please note that Standard Deviation (SD) Score is a term used in growth studies. The SD Score is calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child.
Time Frame One Year
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects who completed 12 months of treatment in the untreated control, 80 and 120 µg/kg BID groups with a baseline height measurement and at least one on-treatment height measurement. Subjects assigned to 40 μg/kg BID arm were excluded from the analysis due to the dose change to 120 μg/kg BID.
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description:
Observational Group
Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm.
Injection of rhIGF-1 80 μg/kg BID
Injection of rhIGF-1 120 μg/kg BID
Overall Number of Participants Analyzed 21 0 39 43
Mean (Standard Deviation)
Unit of Measure: SD/year
0.02  (0.24) 0.39  (0.17) 0.53  (0.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Untreated, 80 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The two-sided p-values for the comparisons are adjusted for multiple comparisons using Dunnett’s method.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.37
Confidence Interval 95%
0.25 to 0.50
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.06
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Untreated, 120 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares each of the 80 and 120 µg/kg BID groups with the untreated control group using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The two-sided p-values for the comparisons are adjusted for multiple comparisons using Dunnett’s method.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.52
Confidence Interval 95%
0.39 to 0.64
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.06
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 80 μg/kg BID (Twice Daily Dosing), 120 μg/kg BID (Twice Daily Dosing)
Comments The analysis compares the 80 and 120 µg/kg BID groups using analysis of covariance (ANCOVA), where the covariates are the baseline height SD score stratum used in the randomization, the pretreatment height velocity, the baseline bone age, the baseline chronological age, and sex.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0071
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.15
Confidence Interval 95%
0.04 to 0.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.06
Estimation Comments [Not Specified]
Time Frame Adverse events were collected until 30 days after last subject visit or until resolution. Adverse event collection for an individual subject was 1 year 1 month. Across study adverse event reporting continued for a total of 4 years 5 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Hide Arm/Group Description Observational Group Injection of rhIGF-1 40 μg/kg BID. Per protocol amendment these subjects were reassigned to receive 120 μg/kg BID. Due to the dose change, the efficacy results for these subjects were analysed in a separate subanalysis. For all outcome measures, mean and standard deviations were not calculated for this arm. Injection of rhIGF-1 80 μg/kg BID Injection of rhIGF-1 120 μg/kg BID
All-Cause Mortality
Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/25 (4.00%)      1/16 (6.25%)      2/44 (4.55%)      5/51 (9.80%)    
Congenital, familial and genetic disorders         
Cor Triatriatum * 1  0/25 (0.00%)  0 0/16 (0.00%)  0 0/44 (0.00%)  0 1/51 (1.96%)  1
Endocrine disorders         
Hypoglycemic seizure * 1  0/25 (0.00%)  0 0/16 (0.00%)  0 0/44 (0.00%)  0 1/51 (1.96%)  1
Gastrointestinal disorders         
Gastroenteritis * 1  0/25 (0.00%)  0 1/16 (6.25%)  1 0/44 (0.00%)  0 0/51 (0.00%)  0
Gastroenteritis escherichia coli * 1  0/25 (0.00%)  0 0/16 (0.00%)  0 1/44 (2.27%)  1 0/51 (0.00%)  0
Vomiting * 1  0/25 (0.00%)  0 1/16 (6.25%)  1 0/44 (0.00%)  0 0/51 (0.00%)  0
Infections and infestations         
Cellulitis * 1  1/25 (4.00%)  1 0/16 (0.00%)  0 0/44 (0.00%)  0 0/51 (0.00%)  0
Gastroenteritis viral * 1  0/25 (0.00%)  0 0/16 (0.00%)  0 0/44 (0.00%)  0 1/51 (1.96%)  1
Pneumonia * 1  0/25 (0.00%)  0 0/16 (0.00%)  0 0/44 (0.00%)  0 1/51 (1.96%)  1
Metabolism and nutrition disorders         
Dehydration * 1  0/25 (0.00%)  0 0/16 (0.00%)  0 0/44 (0.00%)  0 1/51 (1.96%)  1
Nervous system disorders         
Benign Itracranial Hypertension  1  0/25 (0.00%)  0 0/16 (0.00%)  0 0/44 (0.00%)  0 1/51 (1.96%)  1
Intracranial pressure increased  1  0/25 (0.00%)  0 0/16 (0.00%)  0 1/44 (2.27%)  1 0/51 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.00
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Untreated 40 μg/kg BID (Twice Daily Dosing) 80 μg/kg BID (Twice Daily Dosing) 120 μg/kg BID (Twice Daily Dosing)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/25 (72.00%)      16/16 (100.00%)      37/44 (84.09%)      43/51 (84.31%)    
Ear and labyrinth disorders         
Ear infection * 1  0/25 (0.00%)  0 1/16 (6.25%)  3 1/44 (2.27%)  1 6/51 (11.76%)  8
Ear pain * 1  2/25 (8.00%)  2 1/16 (6.25%)  1 3/44 (6.82%)  3 1/51 (1.96%)  2
Gastrointestinal disorders         
Nausea * 1  0/25 (0.00%)  0 4/16 (25.00%)  5 6/44 (13.64%)  7 2/51 (3.92%)  2
Gastroenteritis * 1  0/25 (0.00%)  0 3/16 (18.75%)  4 4/44 (9.09%)  7 3/51 (5.88%)  4
General disorders         
Injection site bruising * 1  0/25 (0.00%)  0 3/16 (18.75%)  3 6/44 (13.64%)  10 4/51 (7.84%)  7
Injection site pain * 1  0/25 (0.00%)  0 2/16 (12.50%)  2 7/44 (15.91%)  7 4/51 (7.84%)  6
Infections and infestations         
Upper respiratory tract infection * 1  6/25 (24.00%)  7 3/16 (18.75%)  5 10/44 (22.73%)  17 12/51 (23.53%)  13
Nasopharyngitis * 1  2/25 (8.00%)  3 2/16 (12.50%)  3 5/44 (11.36%)  5 7/51 (13.73%)  12
Gastroenteritis viral * 1  0/25 (0.00%)  0 3/16 (18.75%)  4 8/44 (18.18%)  10 3/51 (5.88%)  3
Pharyngitis streptococcal * 1  2/25 (8.00%)  2 1/16 (6.25%)  1 4/44 (9.09%)  6 7/51 (13.73%)  9
Influenza * 1  1/25 (4.00%)  1 1/16 (6.25%)  1 4/44 (9.09%)  7 7/51 (13.73%)  10
Otitis media * 1  3/25 (12.00%)  3 3/16 (18.75%)  3 2/44 (4.55%)  3 4/51 (7.84%)  6
Sinusitis * 1  3/25 (12.00%)  4 0/16 (0.00%)  0 1/44 (2.27%)  1 4/51 (7.84%)  8
Metabolism and nutrition disorders         
Hypoglycemia  1 [1]  1/25 (4.00%)  1 2/16 (12.50%)  4 3/44 (6.82%)  3 9/51 (17.65%)  10
Musculoskeletal and connective tissue disorders         
Pain in extremity * 1  1/25 (4.00%)  1 1/16 (6.25%)  1 3/44 (6.82%)  5 6/51 (11.76%)  7
Nervous system disorders         
Headache * 1  4/25 (16.00%)  9 8/16 (50.00%)  16 13/44 (29.55%)  30 21/51 (41.18%)  35
Respiratory, thoracic and mediastinal disorders         
Cough * 1  4/25 (16.00%)  7 4/16 (25.00%)  6 10/44 (22.73%)  17 7/51 (13.73%)  7
Nasal congestion * 1  0/25 (0.00%)  0 4/16 (25.00%)  5 5/44 (11.36%)  6 5/51 (9.80%)  7
Pharyngolaryngeal pain * 1  0/25 (0.00%)  0 3/16 (18.75%)  3 4/44 (9.09%)  4 4/51 (7.84%)  4
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.00
[1]
In order to avoid under-reporting hypoglycemia, transient symptoms with no accompanying blood glucose measurements were also reported as "hypoglycemia" or "hypoglycemia/decreased blood glucose".
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.
Each investigator may publish or report data from their own subjects. The trial data in aggregate are the property of Tercica, Inc. and may not be published without permission of Tercica, Inc. Tercica, Inc. will be the final arbitrator of issues relating to the publication or presentation of the aggregate data.
Results Point of Contact
Name/Title: Medical Director, Pediatric Endocrinology
Organization: Ipsen
Phone: clinical.trials@ipsen.com
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT00125164     History of Changes
Other Study ID Numbers: MS301
First Submitted: July 27, 2005
First Posted: July 29, 2005
Results First Submitted: July 8, 2009
Results First Posted: April 30, 2010
Last Update Posted: June 21, 2012