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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ipsen
ClinicalTrials.gov Identifier:
NCT00572156
First received: December 10, 2007
Last updated: April 30, 2012
Last verified: April 2012
  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: during the first year of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in height SDS [ Time Frame: during the first year of treatment ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Changes in serum concentrations of GH, IGF-1, IGFBP-1, IGFPB-3, ALS and GHBP [ Time Frame: during treatment ] [ Designated as safety issue: No ]
  • Change in bone age [ Time Frame: during treatment ] [ Designated as safety issue: No ]
  • Total change in height divided by total change in chronological age [ Time Frame: From year 2 until the end of the study ] [ Designated as safety issue: No ]
  • Total change in height SDS divided by total change in chronological age [ Time Frame: From year 2 until the end of the study ] [ Designated as safety issue: No ]
  • Total change in predicted adult height divided by the total change in chronological age [ Time Frame: From year 2 until the end of the study ] [ Designated as safety issue: No ]

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
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

Additional 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
Last Updated: April 30, 2012
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, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 14, 2014