Clinical trial NCT00572156: rhGH and rhIGF-1 Combination Therapy in Children With Short Stature Associated With IGF-1 Deficiency
Official title: Recombinant Human Growth Hormone (rhGH) and Recombinant Human Insulin-like Growth Factor-1 rhIGF-1) Combination Therapy in Children With Short Stature Associated With IGF-1 Deficiency: A Six-year, Randomized, Multi-center, Open-label, Parallel-group, Active Treatment Controlled, Dose Selection Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Insulin-like Growth Factor-1 Deficiency
Keywords: IGF-1 Deficiency
growth
ISS
Constitutional growth delay
Primary IGFD
Primary IGF Deficiency
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2007-12-12
Enrollment: 106
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: IGF-1 (insulin-like growth factor-1) is a hormone that is normally produced in the body in response to another hormone called growth hormone. Growth Hormone is produced by a small gland at the base of the brain (the pituitary). Together IGF-1 and GH are large contributors to growth during infancy, childhood, and adolescence.

Children with IGF Deficiency are short and have an imbalance in the levels of growth hormone and IGF-1 that their body produces. Their growth hormone levels are normal or even high, but IGF-1 levels do not increase normally in response to growth hormone. As a result, they have a type of growth hormone insensitivity and an inability to grow normally.

This study is a test to see whether daily dosing with a combination of rhIGF-1 and rhGH will help children with IGFD grow taller more quickly than children treated with rhGH alone. The study medications, rhIGF-1 and rhGH, are approved by the US Food and Drug Administration (FDA) for use in some growth disorders in children, but the combination of rhIGF-1 and rhGH in children with IGF-1 deficiency (IGFD) is investigational.


Eligibility criteria: Inclusion Criteria:

* Parents or legally authorized representatives must give signed informed consent before any trial-related activities
* IGF-1 SDS of ≤ -1 for age and gender
* Short stature, as defined by a height SDS of ≤ -2 for age and gender
* Chronological age ≥ 5 years
* Bone age ≤ 11 years in boys and ≤ 9 years in girls
* GH sufficiency, defined as a maximal stimulated GH response of greater than or equal to 10 ng/mL at Visit 2 (note: upon approval of the Medical Monitor, the result of a prior GH stimulation test may satisfy this requirement).
* Prepubertal status
* Adequate nutrition as evidenced by a body mass index (BMI) greater than or equal to the 5th percentile for age and gender

Exclusion Criteria:

* Severe Primary IGFD (defined as height and IGF-1 SDS ≤ 3, and stimulated GH response greater than or equal to 10 ng/mL)
* Prior or current use of medications with the potential to alter growth patterns including GH, IGF-1, IGFBP-3, gonadotrophin agonists (e.g., Lupron), aromatase inhibitors, androgens and estrogens
* Known or suspected allergy to rhGH, rhIGF-1 or a constituent of their formulations
* Current use of medications for attention deficit disorder
* A chronic health condition that requires anti-inflammatory steroids or daily medication unless approved by the Medical Monitor

Primary outcomes:
measure: Height Velocity
timeFrame: First year of treatment
Secondary outcomes:
measure: Height Velocity
timeFrame: Second, third and fourth year
measure: Cumulative Change in Height Standard Deviation Score (SDS)
timeFrame: First, second, third and fourth year
measure: Predicted Adult Height (PAH)
timeFrame: At baseline (Day 1), year 1,2,3 and 4
measure: Total Change From Baseline (Day 1) in BMI SDS
timeFrame: At year 1,2,3,4 and end of study (visit 23) versus baseline (day 1)
measure: Skeletal Maturation
timeFrame: At baseline(day 1), year 1,2,3 and 4
measure: Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH)
timeFrame: At Baseline (Day 1), Year 1,2,3 and 4
measure: Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1)
timeFrame: At Baseline (Day 1), Year 1,2,3 and 4
measure: Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1)
timeFrame: At Baseline (Day 1), Year 1,2,3 and 4
measure: Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3)
timeFrame: At Baseline (Day 1), Year 1,2,3 and 4
measure: Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS)
timeFrame: At Baseline (Day 1), Year 1,2,3 and 4
measure: Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP)
timeFrame: At Baseline (Day 1), Year 1,2,3 and 4
measure: Summary of Adverse Events With Number of Occurrences
timeFrame: Approximately up to 4 years.
Other outcomes:
Locations:
city: Brisbane
country: United States
facility: Ipsen
state: California
Study officials:
affiliation: Ipsen (formerly Tercica, Inc.)
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: