rhGH and rhIGF-1 Combination Therapy in Children With Short Stature Associated With IGF-1 Deficiency

Phase 2TerminatedNCT00572156

Ipsen106 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

106

Conditions

Insulin-like Growth Factor-1 Deficiency

Interventions

Eligibility

Sex: ALLMin age: 5 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Height Velocity

Time frame: First year of treatment

Secondary Outcomes

Height Velocity

Time frame: Second, third and fourth year

Cumulative Change in Height Standard Deviation Score (SDS)

Height was measured standing and without shoes, and recorded as the mean of three measurements (the subject being repositioned each time) by the same observer using a Harpenden or other wall-mounted stadiometer which was to be calibrated prior to measurement of each subject and a calibration log kept. The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)

Time frame: First, second, third and fourth year

Predicted Adult Height (PAH)

Predicted Adult Height calculated by method, Roche-Wainer-Thissen (RWT) and mid-parental target height SDS. The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)

Time frame: At baseline (Day 1), year 1,2,3 and 4

Total Change From Baseline (Day 1) in BMI SDS

BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)

Time frame: At year 1,2,3,4 and end of study (visit 23) versus baseline (day 1)

Skeletal Maturation

Assessed by bone age. Bone age was determined by the radiograph. The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)

Time frame: At baseline(day 1), year 1,2,3 and 4

Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH)