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

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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

NutropinAq® (Somatropin [rDNA origin])

Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])

About this trial

This is an interventional treatment trial for Insulin-like Growth Factor-1 Deficiency focused on measuring IGF-1 Deficiency, growth, ISS, Constitutional growth delay, Primary IGFD, Primary IGF Deficiency

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Ipsen

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

1. rhGH Alone

2. Combination Dose

3. Combination Dose

4. Combination Dose

Arm Description

Outcomes

Primary Outcome Measures

Height Velocity

Secondary Outcome Measures

Height Velocity

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)

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)

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)

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)

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

Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1)

Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1)

Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3)

Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS)

Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP)

Summary of Adverse Events With Number of Occurrences

A Data Monitoring Committee (DMC) was established to monitor subject safety

Full Information

NCT ID

NCT00572156

First Posted

December 10, 2007

Last Updated

March 3, 2023

Sponsor

Ipsen

1. Study Identification

Unique Protocol Identification Number

NCT00572156

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Terminated

Why Stopped

The study was prematurely terminated due to strategic reasons.

Study Start Date

December 2007 (undefined)

Primary Completion Date

April 2010 (Actual)

Study Completion Date

March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ipsen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Insulin-like Growth Factor-1 Deficiency

Keywords

IGF-1 Deficiency, growth, ISS, Constitutional growth delay, Primary IGFD, Primary IGF Deficiency

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

106 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1. rhGH Alone

Arm Type

Active Comparator

Arm Title

2. Combination Dose

Arm Type

Experimental

Arm Title

3. Combination Dose

Arm Type

Experimental

Arm Title

4. Combination Dose

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

NutropinAq® (Somatropin [rDNA origin])

Other Intervention Name(s)

GH

Intervention Description

rhGH (Somatropin) 45µg/kg once daily injection

Intervention Type

Drug

Intervention Name(s)

Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])

Other Intervention Name(s)

Increlex, rhIGF-1, GH

Intervention Description

rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Intervention Type

Drug

Intervention Name(s)

Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])

Other Intervention Name(s)

Increlex, rhIGF-1, GH

Intervention Description

rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections

Intervention Type

Drug

Intervention Name(s)

Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])

Other Intervention Name(s)

Increlex, rhIGF-1, GH

Intervention Description

rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections

Primary Outcome Measure Information:

Title

Height Velocity

Time Frame

First year of treatment

Secondary Outcome Measure Information:

Title

Height Velocity

Time Frame

Second, third and fourth year

Title

Cumulative Change in Height Standard Deviation Score (SDS)

Description

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

Title

Predicted Adult Height (PAH)

Description

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

Title

Total Change From Baseline (Day 1) in BMI SDS

Description

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)

Title

Skeletal Maturation

Description

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

Title

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

Time Frame