Trial Outcomes & Findings for Recombinant Human Insulin-Like Growth Factor (rhIGF-1) Treatment of Short Stature Associated With IGF-1 Deficiency (NCT NCT00125190)
NCT ID: NCT00125190
Last Updated: 2020-07-27
Results Overview
Height was 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. The subject was repositioned between each measurement. Height velocity during an interval of time is defined as the change in height during the time interval divided by the duration of the time interval. Missing Week 34 heights were imputed using the last height SD score carried forward.
COMPLETED
PHASE2/PHASE3
45 participants
Pretreatment to Week 34
2020-07-27
Participant Flow
This was a open-label, multi-center and single-arm study conducted at 12 investigational sites (11 active) between 12 January 2005 and 14 January 2009. A total of 45 subjects were enrolled in this study.
The screening period consisted of two-staged clinic visits for up to 6 weeks, followed by an open-label treatment period of 86 weeks.
Participant milestones
| Measure |
rhIGF-1 QD
During the treatment phase (Day 1 to Week 86), subjects received subcutaneous (SC) injections of rhIGF-1 at an initial dose of 60 microgram per kilogram (mcg/kg) once daily (QD) starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Overall Study
STARTED
|
45
|
|
Overall Study
Completed 34 Weeks of Study
|
43
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
15
|
Reasons for withdrawal
| Measure |
rhIGF-1 QD
During the treatment phase (Day 1 to Week 86), subjects received subcutaneous (SC) injections of rhIGF-1 at an initial dose of 60 microgram per kilogram (mcg/kg) once daily (QD) starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Overall Study
Subject/Parent Decision
|
7
|
|
Overall Study
Non-compliance
|
2
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Other
|
1
|
|
Overall Study
Lost to Follow-up
|
4
|
Baseline Characteristics
Recombinant Human Insulin-Like Growth Factor (rhIGF-1) Treatment of Short Stature Associated With IGF-1 Deficiency
Baseline characteristics by cohort
| Measure |
rhIGF-1 QD
n=45 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Age, Continuous
|
8.7 years
STANDARD_DEVIATION 2.8 • n=5 Participants
|
|
Age, Customized
Children (2-11 years)
|
36 Participants
n=5 Participants
|
|
Age, Customized
Adolescents (12-17 years)
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
12 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
31 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=5 Participants
|
|
Body Mass Index Standard Deviation (SD) Score
|
-0.4 SDs
STANDARD_DEVIATION 0.7 • n=5 Participants
|
|
Bone Age Imputed
|
7.2 years
STANDARD_DEVIATION 2.6 • n=5 Participants
|
|
Height for Age SD Score
|
-2.7 SDs
STANDARD_DEVIATION 0.6 • n=5 Participants
|
|
IGFBP-3 SD Score
|
-0.7 SDs
STANDARD_DEVIATION 1.0 • n=5 Participants
|
|
IGF-1 SD Score
|
-2.6 SDs
STANDARD_DEVIATION 0.5 • n=5 Participants
|
|
Maximum Stimulated GH
|
20.5 nanogram per milliliter
STANDARD_DEVIATION 9.9 • n=5 Participants
|
|
Weight for Age SD Score
|
-2.3 SDs
STANDARD_DEVIATION 0.7 • n=5 Participants
|
PRIMARY outcome
Timeframe: Pretreatment to Week 34Population: The ITT population included all treated subjects.
Height was 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. The subject was repositioned between each measurement. Height velocity during an interval of time is defined as the change in height during the time interval divided by the duration of the time interval. Missing Week 34 heights were imputed using the last height SD score carried forward.
Outcome measures
| Measure |
rhIGF-1 QD
n=45 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Height Velocity From Pretreatment (Week 0) to Week 34
|
7.0 centimeters per year (cm/yr)
Standard Deviation 1.5
|
PRIMARY outcome
Timeframe: Week 34 to 86Population: The ITT population included all treated subjects. Only subjects in the ITT population who continued past Week 34 were included in the analysis.
Height was 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. The subject was repositioned between each measurement. Height velocity during an interval of time is defined as the change in height during the time interval divided by the duration of the time interval. Missing Week 86 heights were imputed using the last height SD score carried forward.
Outcome measures
| Measure |
rhIGF-1 QD
n=40 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Height Velocity From Week 34 to 86
|
6.7 cm/yr
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: Pretreatment and Week 34Population: The ITT population included all treated subjects.
Height was 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. The subject was repositioned between each measurement. The SD score is calculated as the subject 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.
Outcome measures
| Measure |
rhIGF-1 QD
n=45 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Change in Height SD Score From Pretreatment to Week 34
|
0.21 SDs
Standard Deviation 0.20
|
SECONDARY outcome
Timeframe: Pretreatment and Week 86Population: The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.
Height was 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. Subjects were repositioned between each measurement. 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.
Outcome measures
| Measure |
rhIGF-1 QD
n=40 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Change in Height SD Score From Pretreatment to Week 86
|
0.45 SDs
Standard Deviation 0.39
|
SECONDARY outcome
Timeframe: Pretreatment to Week 86Population: The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.
Plain X-rays of the left hand and wrist were exposed for bone age appraisal. The films were sent to a central facility for standardized evaluation.
Outcome measures
| Measure |
rhIGF-1 QD
n=30 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Change in Bone Age From Pretreatment to Week 86 Minus Change in Chronological Age
|
0.2 years
Standard Deviation 0.68
|
SECONDARY outcome
Timeframe: Pretreatment and Week 86Population: The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.
Growth factor panels for measuring IGFBP-1, IGFBP-2 and IGFBP-3 were evaluated from screening and at each study visit up to Week 86. Inter-quartile range (Q1-Q3) is 10th to 90th percentile.
Outcome measures
| Measure |
rhIGF-1 QD
n=29 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86
IGFBP-1
|
-89.6 percent change
Interval -96.0 to -13.0
|
|
Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86
IGFBP-2
|
37.9 percent change
Interval -25.0 to 227.0
|
|
Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86
IGFBP-3
|
0 percent change
Interval -27.0 to 48.0
|
SECONDARY outcome
Timeframe: Pretreatment and Week 86Population: The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.
Growth factor panels for measuring ALS were evaluated from screening and at each study visit up to Week 86. Inter-quartile range (Q1-Q3) is 10th to 90th percentile.
Outcome measures
| Measure |
rhIGF-1 QD
n=29 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Percent Change in Serum Concentration of ALS From Pretreatment to Week 86
|
-7.7 percent change
Interval -36.0 to 42.0
|
POST_HOC outcome
Timeframe: Pretreatment to Week 34Population: Completer population included all subjects who remained on study to Week 86. Subjects who completed Week 34 were included in the analysis.
Height was 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. The subject was repositioned between each measurement. Height velocity during an interval of time is defined as the change in height during the time interval divided by the duration of the time interval. Missing Week 34 heights were imputed using the last height SD score carried forward.
Outcome measures
| Measure |
rhIGF-1 QD
n=43 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Increase in Height Velocity From Pretreatment to Week 34
|
1.3 cm/yr
Standard Deviation 3.56
|
POST_HOC outcome
Timeframe: Pretreatment to Week 86Population: Completer population included all subjects who remained on study to Week 86.
Height was 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. The subject was repositioned between each measurement. Height velocity during an interval of time is defined as the change in height during the time interval divided by the duration of the time interval. Missing Week 86 heights were imputed using the last height SD score carried forward.
Outcome measures
| Measure |
rhIGF-1 QD
n=30 Participants
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Increase in Height Velocity From Pretreatment to Week 86
|
1.3 cm/yr
Standard Deviation 3.58
|
Adverse Events
rhIGF-1 QD
Serious adverse events
| Measure |
rhIGF-1 QD
n=45 participants at risk
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Infections and infestations
Gastroenteritis
|
2.2%
1/45 • Number of events 1 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Congenital, familial and genetic disorders
Arnold-Chiari Malformation
|
2.2%
1/45 • Number of events 1 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Nervous system disorders
Syringomyelia
|
2.2%
1/45 • Number of events 1 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
Other adverse events
| Measure |
rhIGF-1 QD
n=45 participants at risk
During the treatment phase (Day 1 to Week 86), subjects received SC injections of rhIGF-1 at an initial dose of 60 mcg/kg QD starting on Day 1 (Visit 3). From Week 2 (Visit 4) subsequent dose adjustments were made in order to achieve the target serum IGF-1 concentration for the subject's age and sex. The maximum dose in any circumstance was 240 mcg/kg/day.
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
6.7%
3/45 • Number of events 3 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
6.7%
3/45 • Number of events 4 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
5/45 • Number of events 6 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Gastrointestinal disorders
Stomach Discomfort
|
6.7%
3/45 • Number of events 3 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
18/45 • Number of events 21 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
General disorders
Injection Site Bruising
|
6.7%
3/45 • Number of events 5 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
General disorders
Pyrexia
|
31.1%
14/45 • Number of events 18 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Infections and infestations
Gastroenteritis
|
13.3%
6/45 • Number of events 8 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Infections and infestations
Gastroenteritis Viral
|
6.7%
3/45 • Number of events 4 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Infections and infestations
Influenza
|
11.1%
5/45 • Number of events 6 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
3/45 • Number of events 5 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Infections and infestations
Otitis Media
|
11.1%
5/45 • Number of events 7 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Infections and infestations
Sinusitis
|
8.9%
4/45 • Number of events 4 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
28.9%
13/45 • Number of events 24 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Infections and infestations
Viral Infection
|
15.6%
7/45 • Number of events 13 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
11.1%
5/45 • Number of events 14 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.3%
6/45 • Number of events 8 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Nervous system disorders
Headache
|
40.0%
18/45 • Number of events 32 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
24.4%
11/45 • Number of events 13 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
13.3%
6/45 • Number of events 9 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
|
8.9%
4/45 • Number of events 5 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.7%
3/45 • Number of events 3 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
6.7%
3/45 • Number of events 3 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
|
Skin and subcutaneous tissue disorders
Rash
|
11.1%
5/45 • Number of events 7 • Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER