Recombinant Human Insulin-Like Growth Factor (rhIGF-1) Treatment of Short Stature Associated With IGF-1 Deficiency

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00125190
• Collaborator: (none)
• Enrollment: 45
• Location: 1
• Arm: 1
• Duration (Months): 42.1
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This study is intended to assess the effects of once daily dosing of recombinant human insulin-like growth factor (rhIGF-1) in increasing height velocity.

Condition or Disease	Intervention/Treatment	Phase
Insulin-Like Growth Factor-1 Deficiency; Growth Disorders	Drug: rhIGF-1 (mecasermin) for a period of 86 weeks	Phase 2/Phase 3

Detailed Description

Growth failure associated with primary IGF-1 deficiency (IGFD). Primary IGFD is a term that has been used to describe patients with intrinsic cellular defects in growth hormone (GH) action. In this protocol, primary IGFD is defined as short stature (<-2 standard deviations [SDs] below the mean for age and gender), and abnormal serum IGF-1 (<-2 SDs below the mean for age and gender).

The trial is an open-label, concentration-controlled trial conducted at up to 20 centers throughout the United States.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Recombinant Human Insulin-Like Growth Factor (rhIGF-1) Treatment of Short Stature Associated With Primary IGF-1 Deficiency: A Multi-Center, Open Label, Concentration-Controlled Study
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rhIGF-1 QD Subjects received subcutaneous injection (SC) injections of rhIGF-1 once a day.	Drug: rhIGF-1 (mecasermin) for a period of 86 weeks; Once a day rhIGF-1 injections

Outcome Measures

Primary Outcome Measures

1. Height Velocity From Pretreatment (Week 0) to Week 34 [Pretreatment to Week 34]

   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.

2. Height Velocity From Week 34 to 86 [Week 34 to 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.

Secondary Outcome Measures

1. Change in Height SD Score From Pretreatment to Week 34 [Pretreatment and Week 34]

   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.

2. Change in Height SD Score From Pretreatment to Week 86 [Pretreatment and 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. 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.

3. Change in Bone Age From Pretreatment to Week 86 Minus Change in Chronological Age [Pretreatment to Week 86]

   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.

4. Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86 [Pretreatment and Week 86]

   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.

5. Percent Change in Serum Concentration of ALS From Pretreatment to Week 86 [Pretreatment and Week 86]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Chronological age ≥ 3

• Chronological age or bone age ≤ 12 for boys and ≤ 11 for girls

• Prepubertal at Visit 1

• Height SD score of < -2

• IGF-1 SD score of < -2

Exclusion Criteria:

• Prior treatment with GH, IGF-1, or other growth-influencing medications

• Growth failure associated with other identifiable causes (e.g., syndromes, chromosomal abnormality)

• Chronic illness such as diabetes, cystic fibrosis, etc.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ipsen	Brisbane	California	United States	94005

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Study Director, M.D., Ipsen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT00125190
• Other Study ID Numbers: MS308; 2019-001095-11
• First Posted: Jul 29, 2005
• Last Update Posted: Jul 27, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Ipsen: Primary IGF-1 Deficiency; IGF-1
• Additional relevant MeSH terms: Dwarfism; Growth Disorders; Mecasermin

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	The screening period consisted of two-staged clinic visits for up to 6 weeks, followed by an open-label treatment period of 86 weeks.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Period Title: Overall Study
STARTED	45
Completed 34 Weeks of Study	43
COMPLETED	30
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Overall Participants	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.7 (2.8)
Age, Customized (Count of Participants)
Children (2-11 years)	36 80%
Adolescents (12-17 years)	9 20%
Sex: Female, Male (Count of Participants)
Female	7 15.6%
Male	38 84.4%
Race/Ethnicity, Customized (participants) [Number]
Black	1 2.2%
Hispanic	12 26.7%
White	31 68.9%
Other	1 2.2%
Body Mass Index Standard Deviation (SD) Score (SDs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [SDs]	-0.4 (0.7)
Bone Age Imputed (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.2 (2.6)
Height for Age SD Score (SDs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [SDs]	-2.7 (0.6)
IGFBP-3 SD Score (SDs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [SDs]	-0.7 (1.0)
IGF-1 SD Score (SDs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [SDs]	-2.6 (0.5)
Maximum Stimulated GH (nanogram per milliliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nanogram per milliliter]	20.5 (9.9)
Weight for Age SD Score (SDs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [SDs]	-2.3 (0.7)

Outcome Measures

1. Primary Outcome

Title	Height Velocity From Pretreatment (Week 0) to Week 34
Description	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.
Time Frame	Pretreatment to Week 34

Outcome Measure Data

Analysis Population Description

The ITT population included all treated subjects.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Measure Participants	45
Mean (Standard Deviation) [centimeters per year (cm/yr)]	7.0 (1.5)

2. Primary Outcome

Title	Height Velocity From Week 34 to 86
Description	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.
Time Frame	Week 34 to 86

Outcome Measure Data

Analysis Population Description

The ITT population included all treated subjects. Only subjects in the ITT population who continued past Week 34 were included in the analysis.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Measure Participants	40
Mean (Standard Deviation) [cm/yr]	6.7 (1.8)

3. Secondary Outcome

Title	Change in Height SD Score From Pretreatment to Week 34
Description	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.
Time Frame	Pretreatment and Week 34

Outcome Measure Data

Analysis Population Description

The ITT population included all treated subjects.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Measure Participants	45
Mean (Standard Deviation) [SDs]	0.21 (0.20)

4. Secondary Outcome

Title	Change in Height SD Score From Pretreatment to Week 86
Description	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.
Time Frame	Pretreatment and Week 86

Outcome Measure Data

Analysis Population Description

The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Measure Participants	40
Mean (Standard Deviation) [SDs]	0.45 (0.39)

5. Secondary Outcome

Title	Change in Bone Age From Pretreatment to Week 86 Minus Change in Chronological Age
Description	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.
Time Frame	Pretreatment to Week 86

Outcome Measure Data

Analysis Population Description

The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Measure Participants	30
Mean (Standard Deviation) [years]	0.2 (0.68)

6. Secondary Outcome

Title	Percent Change in Serum Concentration of IGFBP-1, IGFBP-2 and IGFBP-3 From Pretreatment to Week 86
Description	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.
Time Frame	Pretreatment and Week 86

Outcome Measure Data

Analysis Population Description

The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Measure Participants	29
IGFBP-1	-89.6
IGFBP-2	37.9
IGFBP-3	0

7. Secondary Outcome

Title	Percent Change in Serum Concentration of ALS From Pretreatment to Week 86
Description	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.
Time Frame	Pretreatment and Week 86

Outcome Measure Data

Analysis Population Description

The ITT population included all treated subjects. Only subjects who had both pretreatment and Week 86 measurements were included in the analysis.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Measure Participants	29
Median (Inter-Quartile Range) [percent change]	-7.7

8. Post-Hoc Outcome

Title	Increase in Height Velocity From Pretreatment to Week 34
Description	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.
Time Frame	Pretreatment to Week 34

Outcome Measure Data

Analysis Population Description

Completer population included all subjects who remained on study to Week 86. Subjects who completed Week 34 were included in the analysis.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
Measure Participants	43
Mean (Standard Deviation) [cm/yr]	1.3 (3.56)

9. Post-Hoc Outcome

Title	Increase in Height Velocity From Pretreatment to Week 86
Description	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.
Time Frame	Pretreatment to Week 86

Outcome Measure Data

Analysis Population Description

Completer population included all subjects who remained on study to Week 86.

Arm/Group Title	rhIGF-1 QD
Arm/Group Description	During the treatment phase, subjects received subcutaneous (SC) injections of rhIGF-1 at an initial dose of 60 µg/kg QD, with subsequent dose adjustments 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.
Measure Participants	30
Mean (Standard Deviation) [cm/yr]	1.3 (3.58)

Adverse Events

Time Frame	Treatment emergent adverse events were collected from Day 1 to Week 86 (approximately 21 months).
Arm/Group Title	rhIGF-1 QD
Arm/Group Description	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.
All Cause Mortality
	rhIGF-1 QD
	Affected / at Risk (%)	# Events
Total	0/45 (0%)
Serious Adverse Events
	rhIGF-1 QD
	Affected / at Risk (%)	# Events
Total	2/45 (4.4%)
Congenital, familial and genetic disorders
Arnold-Chiari Malformation	1/45 (2.2%)	1
Infections and infestations
Gastroenteritis	1/45 (2.2%)	1
Nervous system disorders
Syringomyelia	1/45 (2.2%)	1
Other (Not Including Serious) Adverse Events
	rhIGF-1 QD
	Affected / at Risk (%)	# Events
Total	41/45 (91.1%)
Gastrointestinal disorders
Abdominal Pain	3/45 (6.7%)	3
Abdominal Pain Upper	3/45 (6.7%)	4
Diarrhoea	5/45 (11.1%)	6
Stomach Discomfort	3/45 (6.7%)	3
Vomiting	18/45 (40%)	21
General disorders
Injection Site Bruising	3/45 (6.7%)	5
Pyrexia	14/45 (31.1%)	18
Infections and infestations
Gastroenteritis	6/45 (13.3%)	8
Gastroenteritis Viral	3/45 (6.7%)	4
Influenza	5/45 (11.1%)	6
Nasopharyngitis	3/45 (6.7%)	5
Otitis Media	5/45 (11.1%)	7
Sinusitis	4/45 (8.9%)	4
Upper Respiratory Tract Infection	13/45 (28.9%)	24
Viral Infection	7/45 (15.6%)	13
Metabolism and nutrition disorders
Hypoglycaemia	5/45 (11.1%)	14
Musculoskeletal and connective tissue disorders
Arthralgia	6/45 (13.3%)	8
Nervous system disorders
Headache	18/45 (40%)	32
Respiratory, thoracic and mediastinal disorders
Cough	11/45 (24.4%)	13
Nasal Congestion	6/45 (13.3%)	9
Pharyngolaryngeal Pain	4/45 (8.9%)	5
Rhinorrhoea	3/45 (6.7%)	3
Skin and subcutaneous tissue disorders
Dermatitis Contact	3/45 (6.7%)	3
Rash	5/45 (11.1%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.