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

March 3, 2023 updated by: Ipsen

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

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 Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

106

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Brisbane, California, United States, 94005
        • Ipsen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1. rhGH Alone
Drug: NutropinAq® (Somatropin [rDNA origin])
rhGH (Somatropin) 45µg/kg once daily injection
Other Names:
  • GH
Experimental: 2. 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:
  • GH
  • Increlex
  • rhIGF-1
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:
  • GH
  • Increlex
  • rhIGF-1
Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
Other Names:
  • GH
  • Increlex
  • rhIGF-1
Experimental: 3. 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:
  • GH
  • Increlex
  • rhIGF-1
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:
  • GH
  • Increlex
  • rhIGF-1
Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
Other Names:
  • GH
  • Increlex
  • rhIGF-1
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:
  • GH
  • Increlex
  • rhIGF-1
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:
  • GH
  • Increlex
  • rhIGF-1
Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
Other Names:
  • GH
  • Increlex
  • rhIGF-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Height Velocity
Time Frame: First year of treatment
First year of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Height Velocity
Time Frame: Second, third and fourth year
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)
First, second, third and fourth year
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)
At baseline (Day 1), year 1,2,3 and 4
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)
At year 1,2,3,4 and end of study (visit 23) versus baseline (day 1)
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)
At baseline(day 1), year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH)
Time Frame: At Baseline (Day 1), Year 1,2,3 and 4
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
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
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
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
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
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
Approximately up to 4 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ipsen

Investigators

  • Study Director: Ipsen Medical Director, Ipsen (formerly Tercica, Inc.)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

December 10, 2007

First Submitted That Met QC Criteria

December 10, 2007

First Posted (Estimate)

December 12, 2007

Study Record Updates

Last Update Posted (Actual)

March 30, 2023

Last Update Submitted That Met QC Criteria

March 3, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MS316
  • 2019-000843-29 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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