Growth Hormone Insensitivity Syndrome
Conditions
Keywords
growth, insulin like growth factor, Laron syndrome
Brief summary
The objective of this study was to evaluate the long-term safety and effectiveness of mecasermin (the study drug) in children with growth failure due to severe Primary insulin-like growth factor-1 deficiency (Primary IGFD).
Interventions
DRUGmecasermin
injections BID of rhIGF-1, mecasermin
Sponsors
University of Oklahoma
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Height \<-2SD for age and gender * IGF-1 \<-2SD for age and gender * Evidence of GH resistance
Exclusion criteria
* closed epiphyses * prior active malignancy * major organ disfunction * treatment with medications that would diminish growth * clinically significant cardiac abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Height Velocity Up to 12 Years | Baseline (Pre-dose) and up to 12 years | Height velocity is the difference between 2 height measurements, divided by years elapsed between measurements. |
| Number of Naive Participants With Height Velocity <5 cm/y at the End of 1 Year of Study Treatment | Baseline (Pre-dose) and 1 year | Height measurements were performed using wall-mounted stadiometers for analysis of growth data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Height Velocity Standard Deviation Score Up to 12 Years | Baseline (Pre-dose) and up to 12 years | Center for disease control growth charts from the US were used as reference for age and gender-dependent mean and standard deviation. Height velocity-standard deviation score was calculated as height velocity minus reference mean height velocity divided by standard deviation of the reference mean height velocity. Greater height velocity standard deviation score indicates better outcome. |
| Height Standard Deviation Score Up to 12 Years | Baseline (Pre-dose) and up to 12 years | Center for disease control growth charts from the US were used as reference for age and gender-dependent mean and standard deviation. Height standard deviation score was calculated as height minus reference mean height divided by standard deviation of the reference mean height. A higher height standard deviation score indicates a better outcome. |
| Approximate Increase in Height Over Expected for Naïve Participants With Near-Adult Height | Baseline (Pre-dose) and up to 19 years | Height measurements were performed using wall-mounted stadiometers for analysis of growth data. |
Countries
United States
Participant flow
Recruitment details
This Phase 3, open-label study was conducted in children with short stature due to severe primary insulin like growth factor-1 deficiency at 2 investigative sites in the US in conjunction with sites in 23 other countries (Argentina, Australia, Austria, Bahamas, Brazil, Canada, Egypt, France, Germany, Iran, Israel, Italy, Kuwait, Pakistan, Poland, Russia, Saudi Arabia, Spain, Sweden, Syria, Taiwan, Ukraine, and Yemen).
Pre-assignment details
Participants who had been treated with mecasermin in previous Genentech-sponsored studies (F0206s, F0375g, F0632g, F0671g), as well as new participants naïve to mecasermin treatment, were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Mecasermin Participants who were entered from previous studies continued to receive mecasermin 80 to 120 mcg/kg SC twice daily and naïve-to-treatment participants were administered mecasermin 60 to 80 mcg/kg SC twice daily for 1 to 2 weeks, and then increased to 120 mcg/kg as tolerated. | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not enter in this study | 1 |
| Overall Study | Lost to Follow-up | 30 |
| Overall Study | Non-compliance | 4 |
| Overall Study | On-treatment at end of study | 8 |
| Overall Study | Parent/patient decision | 2 |
| Overall Study | Participant transferred to commercial drug | 14 |
| Overall Study | Poor growth | 1 |
| Overall Study | Unable to provide study drug | 6 |
Baseline characteristics
| Characteristic | Mecasermin |
|---|---|
| Age, Continuous | 7.6 years STANDARD_DEVIATION 4.3 |
| Race/Ethnicity, Customized African American | 3 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 77 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 92 |
| other Total, other adverse events | 73 / 92 |
| serious Total, serious adverse events | 18 / 92 |
Outcome results
Primary
Annualized Height Velocity Up to 12 Years
Height velocity is the difference between 2 height measurements, divided by years elapsed between measurements.
Time frame: Baseline (Pre-dose) and up to 12 years
Population: The intention-to-treat population consisted of all 92 participants. Only data from the participants naïve to exogenous recombinant human insulin-like growth factor-1 (rhIGF-1) and whose pre-treatment height velocity were available were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 10 years | 4.5 centimeter per year (cm/y) | Standard Deviation 2 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 9 years | 4.4 centimeter per year (cm/y) | Standard Deviation 1.7 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 11 years | 4.1 centimeter per year (cm/y) | Standard Deviation 2 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 12 years | 3.9 centimeter per year (cm/y) | Standard Deviation 2 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | Baseline (Pre-dose) | 2.6 centimeter per year (cm/y) | Standard Deviation 1.7 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 1 year | 8.0 centimeter per year (cm/y) | Standard Deviation 2.3 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 2 years | 5.9 centimeter per year (cm/y) | Standard Deviation 1.7 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 3 years | 5.5 centimeter per year (cm/y) | Standard Deviation 1.8 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 4 years | 5.2 centimeter per year (cm/y) | Standard Deviation 1.5 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 5 years | 4.9 centimeter per year (cm/y) | Standard Deviation 1.5 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 6 years | 4.8 centimeter per year (cm/y) | Standard Deviation 1.4 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 7 years | 4.3 centimeter per year (cm/y) | Standard Deviation 1.5 |
| Mecasermin | Annualized Height Velocity Up to 12 Years | >= 8 years | 4.4 centimeter per year (cm/y) | Standard Deviation 1.5 |
Primary
Number of Naive Participants With Height Velocity <5 cm/y at the End of 1 Year of Study Treatment
Height measurements were performed using wall-mounted stadiometers for analysis of growth data.
Time frame: Baseline (Pre-dose) and 1 year
Population: The intention-to-treat population consisted of all 92 participants. Only data from the participants naïve to exogenous rhIGF-1 were reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mecasermin | Number of Naive Participants With Height Velocity <5 cm/y at the End of 1 Year of Study Treatment | 7 Participants |
Secondary
Approximate Increase in Height Over Expected for Naïve Participants With Near-Adult Height
Height measurements were performed using wall-mounted stadiometers for analysis of growth data.
Time frame: Baseline (Pre-dose) and up to 19 years
Population: The intention-to-treat population consisted of all 92 participants. Only data from the participants naïve to exogenous rhIGF-1 and who attained near adult height were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mecasermin | Approximate Increase in Height Over Expected for Naïve Participants With Near-Adult Height | 13.3 cm | Standard Deviation 8.4 |
Secondary
Height Standard Deviation Score Up to 12 Years
Center for disease control growth charts from the US were used as reference for age and gender-dependent mean and standard deviation. Height standard deviation score was calculated as height minus reference mean height divided by standard deviation of the reference mean height. A higher height standard deviation score indicates a better outcome.
Time frame: Baseline (Pre-dose) and up to 12 years
Population: The intention-to-treat population consisted of all 92 participants. Only data from the participants naïve to exogenous rhIGF-1 were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 3 years | -5.3 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 12 years | -4.4 Standard deviation score | Standard Deviation 1.3 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | Baseline (Pre-dose) | -6.9 Standard deviation score | Standard Deviation 1.8 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 1 year | -6.1 Standard deviation score | Standard Deviation 1.8 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 2 years | -5.6 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 4 years | -5.1 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 5 years | -5.0 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 6 years | -4.9 Standard deviation score | Standard Deviation 1.6 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 7 years | -4.9 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 8 years | -5.1 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 9 years | -5.0 Standard deviation score | Standard Deviation 1.6 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 10 years | -5.0 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Standard Deviation Score Up to 12 Years | >= 11 years | -4.7 Standard deviation score | Standard Deviation 1.2 |
Secondary
Height Velocity Standard Deviation Score Up to 12 Years
Center for disease control growth charts from the US were used as reference for age and gender-dependent mean and standard deviation. Height velocity-standard deviation score was calculated as height velocity minus reference mean height velocity divided by standard deviation of the reference mean height velocity. Greater height velocity standard deviation score indicates better outcome.
Time frame: Baseline (Pre-dose) and up to 12 years
Population: The intention-to-treat population consisted of all 92 participants. Only data from the participants naïve to exogenous rhIGF-1 and whose pre-treatment height velocity were available were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | Baseline (Pre-dose) | -3.4 Standard deviation score | Standard Deviation 1.6 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 1 year | 1.7 Standard deviation score | Standard Deviation 2.8 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 2 years | -0.0 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 3 years | -0.1 Standard deviation score | Standard Deviation 1.9 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 4 years | -0.2 Standard deviation score | Standard Deviation 1.9 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 5 years | -0.3 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 6 years | -0.2 Standard deviation score | Standard Deviation 1.6 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 7 years | -0.5 Standard deviation score | Standard Deviation 1.7 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 8 years | -0.2 Standard deviation score | Standard Deviation 1.6 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 9 years | -0.4 Standard deviation score | Standard Deviation 0.8 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 10 years | 0.1 Standard deviation score | Standard Deviation 1.6 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 11 years | 0.5 Standard deviation score | Standard Deviation 2.6 |
| Mecasermin | Height Velocity Standard Deviation Score Up to 12 Years | >= 12 years | -0.1 Standard deviation score | Standard Deviation 1.5 |