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

• ClinicalTrials.gov Identifier: NCT00572156
• Recruitment Status: Terminated
• First Posted: December 12, 2007
• Results First Posted: December 15, 2015
• Last Update Posted: September 9, 2019
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

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.

Condition or disease	Intervention/treatment	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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: December 2007
• Actual Primary Completion Date: April 2010
• Actual Study Completion Date: March 2012

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Height Velocity [ Time Frame: First year of treatment ]

Secondary Outcome Measures :

1. Height Velocity [ Time Frame: Second, third and fourth year ]
2. 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)

3. 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)

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)

5. 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)

6. Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) [ Time Frame: At Baseline (Day 1), Year 1,2,3 and 4 ]
7. 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 ]
8. 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 ]
9. 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 ]
10. 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 ]
11. 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 ]
12. 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

Eligibility Criteria

• Ages Eligible for Study: 5 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, California

Ipsen

Brisbane, California, United States, 94005

Sponsors and Collaborators

Ipsen

Investigators

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

More Information

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT00572156
• Other Study ID Numbers: MS316; 2019-000843-29 ( EudraCT Number )
• First Posted: December 12, 2007
• Results First Posted: December 15, 2015
• Last Update Posted: September 9, 2019
• Last Verified: September 2019

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; Mecasermin; Growth Substances; Physiological Effects of Drugs