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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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, Ran

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.


Detailed Summary:
Sponsor: Ipsen

Current Primary Outcome: Height Velocity [ Time Frame: First year of treatment ]

Original Primary Outcome: Height Velocity [ Time Frame: during the first year of treatment ]

Current Secondary Outcome:

  • Height Velocity [ Time Frame: Second, third and fourth year ]
  • Cumulative Change in Height Standard Deviation Score (SDS) [ Time Frame: First, second, third and fourth year ]

    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)

  • Predicted Adult Height (PAH) [ Time Frame: At baseline (Day 1), year 1,2,3 and 4 ]

    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)

  • Total Change From Baseline (Day 1) in BMI SDS [ Time Frame: At year 1,2,3,4 and end of study (visit 23) versus baseline (day 1) ]

    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)

  • Skeletal Maturation [ Time Frame: At baseline(day 1), year 1,2,3 and 4 ]

    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)

  • Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) [ Time Frame: At Baseline (Day 1), Year 1,2,3 and 4 ]
  • Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) [ Time Frame: At Baseline (Day 1), Year 1,2,3 and 4 ]
  • Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) [ Time Frame: At Baseline (Day 1), Year 1,2,3 and 4 ]
  • Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) [ Time Frame: At Baseline (Day 1), Year 1,2,3 and 4 ]
  • Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) [ Time Frame: At Baseline (Day 1), Year 1,2,3 and 4 ]
  • Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) [ Time Frame: At Baseline (Day 1), Year 1,2,3 and 4 ]
  • Summary of Adverse Events With Number of Occurrences [ Time Frame: Approximately up to 4 years. ]
    A Data Monitoring Committee (DMC) was established to monitor subject safety


Original Secondary Outcome:

  • Change in height SDS [ Time Frame: during the first year of treatment ]
  • Safety assessments including: physical exam, funduscopic exams, adverse events, safety and metabolic labs and anti-GH and anti-IGF-1 antibodies [ Time Frame: during treatment ]
  • Changes in serum concentrations of GH, IGF-1, IGFBP-1, IGFPB-3, ALS and GHBP [ Time Frame: during treatment ]
  • Change in bone age [ Time Frame: during treatment ]
  • Changes in adipokines [ Time Frame: during treatment ]


Information By: Ipsen

Dates:
Date Received: December 10, 2007
Date Started: December 2007
Date Completion:
Last Updated: November 10, 2015
Last Verified: November 2015