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

Sponsor:	Ipsen
Information provided by:	Ipsen
ClinicalTrials.gov Identifier:	NCT00125164

Purpose

This study is intended to determine whether twice daily weight based dosing with recombinant human insulin-like growth factor (rhIGF-1) will safely and effectively increase the growth of prepubertal children with short stature associated with low IGF-1 levels but who produce sufficient growth hormone (GH). Subjects will be randomized to either an observation arm or to active treatment.

Condition	Intervention	Phase
Growth Disorders Insulin-Like Growth Factor-1 Deficiency	Drug: rhIGF-1 (mecasermin, Tercica, Inc.)	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Recombinant Human Insulin-Like Growth Factor (rhIGF-1) Treatment of Prepubertal Children With Growth Failure Associated With Primary IGF-1 Deficiency: A Phase 3, Randomized, Open Label, Observation-Controlled, Multicenter, Parallel-Dose Comparison Trial

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Growth Disorders

Drug Information available for: Insulin Insulin-like growth factor I Mecasermin Mecasermin rinfabate

U.S. FDA Resources

Further study details as provided by Ipsen:

Primary Outcome Measures:

Height Velocity During the First Year - Intent to Treat (ITT)Population [ Time Frame: Measured at baseline and at one year ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Change From Baseline in Height Standard Deviation (SD) Score at One Year - ITT Population [ Time Frame: Measured at baseline and at one year ] [ Designated as safety issue: No ]
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.
Changes in Bone Age From Baseline to One Year [ Time Frame: Measured at baseline and at one year ] [ Designated as safety issue: Yes ]
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.
Percent Changes From Baseline in Serum Concentrations of IGF-1 at One Year [ Time Frame: Measured at baseline and at one year ] [ Designated as safety issue: No ]
Blood sample was collected while subject is in a fasting state for measuring the level of IGF-1 in the growth factor panel.
Percent Changes From Baseline in Serum Concentrations of IGF-2 at One Year [ Time Frame: Measured at baseline and at one year ] [ Designated as safety issue: No ]
Blood sample was collected for measuring the level of IGF-2 in the growth factor panel.
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 ] [ Designated as safety issue: No ]
Blood sample was collected for measuring the level of insulin-like growth factor binding protein-2 (IGFBP-2) in the growth factor panel.
Percent Changes From Baseline in Serum Concentrations of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) at One Year [ Time Frame: Measured at baseline and at one year ] [ Designated as safety issue: No ]
Blood sample was collected while subject is in a fasting state for measuring the level of IGFBP-3 in the growth factor panel.
IGF Generation Test: Change of Serum IGF-1 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) [ Time Frame: Study Day 1 and Day 7 ] [ Designated as safety issue: No ]
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.
IGF Generation Test: Change of Serum IGFBP-3 After 7 Days Exposure to Recombinant Human Growth Hormone (rhGH) [ Time Frame: Study Day 1 and Day 7 ] [ Designated as safety issue: No ]
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.

Enrollment:	137
Study Start Date:	March 2004
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: Untreated Observational Group
Experimental: 40 μg/kg BID (twice daily dosing) 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.	Drug: rhIGF-1 (mecasermin, Tercica, Inc.) Twice Daily Injection
Experimental: 80 μg/kg BID (twice daily dosing) Injection of rhIGF-1 80 μg/kg BID	Drug: rhIGF-1 (mecasermin, Tercica, Inc.) Twice Daily Injection
Experimental: 120 μg/kg BID (twice daily dosing) Injection of rhIGF-1 120 μg/kg BID	Drug: rhIGF-1 (mecasermin, Tercica, Inc.) Twice Daily Injection

Detailed Description:

Prepubertal 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 GH action. In this protocol, primary IGFD is defined as short stature (height standard deviation score[SDS]<-2 below the mean for age and gender), low serum IGF-1 (IGF-1 SDS <-2 below the mean for age and gender), and levels of growth hormone (GH) that are normal (≥7ng/mL) after a GH stimulation test. Primary IGFD is believed to result from a lower than normal ability to produce IGF-1 when exposed to normal levels of GH, i.e., a type of GH insensitivity or GH resistance.

This trial is one year, randomized, open label, observation-controlled, parallel-dose comparison efficacy and safety study conducted in approximately 40 centers across the United States.

Eligibility

Ages Eligible for Study:	3 Years to 12 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Chronological age ≥ 3 and chronological or bone age less than or equal to 11 years inclusive in girls;
Chronological age ≥ 3 and chronological or bone age less than or equal to 12 years inclusive for boys
Prepubertal
Height SD score of < -2
IGF-1 SD score of < -2

Exclusion Criteria:

Prior treatment with rhGH, rhIGF-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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00125164

Locations

United States, California
Ipsen (formerly Tercica)
Brisbane, California, United States, 94005

Sponsors and Collaborators

Ipsen

Investigators

Study Director:

Ipsen Study Director, M.D.

Ipsen

More Information

No publications provided

Responsible Party:	Cathryn Clary, MD, Ipsen
ClinicalTrials.gov Identifier:	NCT00125164 History of Changes
Other Study ID Numbers:	MS301
Study First Received:	July 27, 2005
Results First Received:	July 8, 2009
Last Updated:	March 17, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Ipsen:

Primary IGF-1 Deficiency

Additional relevant MeSH terms:

Failure to Thrive
Growth Disorders
Pathologic Processes
Mitogens

Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012