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

This study has been terminated.
(The study was prematurely terminated due to strategic reasons.)
Sponsor:
Information provided by (Responsible Party):
Ipsen
ClinicalTrials.gov Identifier:
NCT00572156
First received: December 10, 2007
Last updated: November 10, 2015
Last verified: November 2015
  Purpose

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.


Condition Intervention Phase
Insulin-like Growth Factor-1 Deficiency
Drug: NutropinAq® (Somatropin [rDNA origin])
Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
Phase 2

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 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

Resource links provided by NLM:


Further study details as provided by Ipsen:

Primary Outcome Measures:
  • Height Velocity [ Time Frame: First year of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Height Velocity [ Time Frame: Second, third and fourth year ] [ Designated as safety issue: No ]
  • Cumulative Change in Height Standard Deviation Score (SDS) [ Time Frame: First, second, third and fourth year ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Summary of Adverse Events With Number of Occurrences [ Time Frame: Approximately up to 4 years. ] [ Designated as safety issue: Yes ]
    A Data Monitoring Committee (DMC) was established to monitor subject safety


Enrollment: 106
Study Start Date: December 2007
Study Completion Date: March 2012
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1. rhGH Alone Drug: NutropinAq® (Somatropin [rDNA origin])
rhGH (Somatropin) 45µg/kg once daily injection
Other Name: GH
Experimental: 2. Combination Dose Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
Other Names:
  • Increlex
  • rhIGF-1
  • GH
Experimental: 3. Combination Dose Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
Other Names:
  • Increlex
  • rhIGF-1
  • GH
Experimental: 4. Combination Dose Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection
Other Names:
  • Increlex
  • rhIGF-1
  • GH

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00572156

Locations
United States, California
Ipsen
Brisbane, California, United States, 94005
Sponsors and Collaborators
Ipsen
Investigators
Study Director: Catherine Lesage, M.D. Ipsen (formerly Tercica, Inc.)
  More Information

No publications provided

Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT00572156     History of Changes
Other Study ID Numbers: MS316 
Study First Received: December 10, 2007
Results First Received: August 6, 2015
Last Updated: November 10, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Ipsen:
IGF-1 Deficiency
growth
ISS
Constitutional growth delay
Primary IGFD
Primary IGF Deficiency

Additional relevant MeSH terms:
Dwarfism
Bone Diseases
Bone Diseases, Developmental
Endocrine System Diseases
Genetic Diseases, Inborn
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on February 11, 2016