Growth Hormone Deficiency
Conditions
Brief summary
Multi-center, randomized, controlled, open-label, phase III study comparing the effects of two different dosages of somatropin treatment (in-label or doubled) after 12 and 24 months of treatment, on height velocity in early pubertal children with growth hormone deficiency (GHD). The study will be conducted in Italy. Approximately 26 subjects will participate in this study, distributed as 13 in the in-label dosage group (group A) and 13 in the doubled dosage group (group B).
Interventions
DRUGSomatropin
Doubled dosage with respect to the pre-enrollment (in-label) dosage
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 14 Years
Healthy volunteers
No
Inclusion criteria
* Height velocity (cm/y) less than 25th percentile at the time of diagnosis. * diagnosis of GHD * Replacement therapy at label dosage (from 0.025 to 0.035 mg/kg/day) must be started at least 1 year before the enrolment in this study, but at most 3 years before enrolment * Bone age less than 12 years for girls and less than 14 years for boys. This assessment should be made by the central reader of bone ages, based on the x-ray taken at Visit 0. * Informed consent obtained from either both of the subject's parents or legal representative.
Exclusion criteria
* Pubertal clinical stage less than 2 and greater than 3 according to Tanner score (for male subjects a volume of testicle greater than 15 mL). * Any evidence of active malignancy. In case of previous surgical removal of both diencephalic and hypophysial masses, an MRI, performed within six months before enrollment into the study, must exclude the growth of residual tumoral tissue. * Any known chronic disease such as diabetes mellitus, hepatic disease (defined by elevated liver enzymes 3-fold the upper limit of normal ranges), renal disease with creatinine levels greater than 130 micromol/L, or congestive heart failure. * Glucocorticoid therapy in supra physiological doses (inhaled corticoids will be accepted if below 3 puffs/day, for no more than 10 days consecutively). * Current or previous therapy with any therapy that may directly influence growth, including growth hormone releasing hormone, estrogens and anabolic steroids.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Height Velocity Standard Deviation Score (SDS) at 12-Month Endpoint | 12-Months | Height velocity (difference between 2 height measurements, divided by years elapsed between measurements) SDS was derived by subtracting age and gender-matched population mean height velocity from patient's height velocity (based on measurements 12 months apart) then dividing this value by age and gender-matched population height velocity SD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 12-Month and 24-Month Endpoints in Height Standard Deviation Score (SDS) | Baseline, 12-Months, 24-Months | This was derived by subtracting the age-and-gender-matched population 50th percentile height from the patient's height and then dividing this value by the age-and-gender-matched population height SD. |
| Height Velocity Standard Deviation Score (SDS) at 24 Month Endpoint | 24 Months | Height velocity (difference between 2 height measurements, divided by years elapsed between measurements) SDS was derived by subtracting age and gender-matched population mean height velocity from patient's height velocity (based on measurements 12 months apart) then dividing this value by age and gender-matched population height velocity SD. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Dose Somatropin Somatropin: 0.05 to 0.07 milligram/kilogram/day subcutaneous injection | 14 |
| Label Dose Somatropin Somatropin: 0.025 to 0.035 milligram/kilogram/day subcutaneous injection | 13 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Participant Moved Away | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Total | High Dose Somatropin | Label Dose Somatropin |
|---|---|---|---|
| Age Continuous | 13.3 years STANDARD_DEVIATION 1.3 | 13.5 years STANDARD_DEVIATION 1.2 | 13.0 years STANDARD_DEVIATION 1.5 |
| Baseline Predicted Height | 168 centimeters STANDARD_DEVIATION 8.7 | 168 centimeters STANDARD_DEVIATION 6.8 | 169 centimeters STANDARD_DEVIATION 10.7 |
| Baseline Predicted Height Standard Deviation Score (SDS) | -0.7 standard deviation score STANDARD_DEVIATION 0.9 | -0.9 standard deviation score STANDARD_DEVIATION 0.8 | -0.5 standard deviation score STANDARD_DEVIATION 1 |
| Body Mass Index | 19.2 kilograms per square meter (kg/m2) STANDARD_DEVIATION 3.4 | 18.9 kilograms per square meter (kg/m2) STANDARD_DEVIATION 3.2 | 19.4 kilograms per square meter (kg/m2) STANDARD_DEVIATION 3.7 |
| Bone Age | 12.2 years STANDARD_DEVIATION 0.8 | 12.4 years STANDARD_DEVIATION 0.7 | 12.1 years STANDARD_DEVIATION 1 |
| Height | 145 centimeters STANDARD_DEVIATION 6.5 | 145 centimeters STANDARD_DEVIATION 5.1 | 146 centimeters STANDARD_DEVIATION 7.8 |
| Height Standard Deviation Score (SDS) | -1.4 standard deviation score STANDARD_DEVIATION 1 | -1.7 standard deviation score STANDARD_DEVIATION 1 | -1.1 standard deviation score STANDARD_DEVIATION 1 |
| Race/Ethnicity Caucasian | 26.0 participants | 14 participants | 12 participants |
| Race/Ethnicity Other | 1.0 participants | 0 participants | 1 participants |
| Region of Enrollment Italy | 27.0 participants | 14 participants | 13 participants |
| Sex: Female, Male Female | 4.0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 23.0 Participants | 13 Participants | 10 Participants |
| Target Height | 168 centimeters STANDARD_DEVIATION 6.2 | 168 centimeters STANDARD_DEVIATION 5 | 168 centimeters STANDARD_DEVIATION 7.5 |
| Target Height Standard Deviation Score (SDS) | -0.8 standard deviation score STANDARD_DEVIATION 0.6 | -0.9 standard deviation score STANDARD_DEVIATION 0.7 | -0.6 standard deviation score STANDARD_DEVIATION 0.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / — | 5 / — |
| serious Total, serious adverse events | 1 / — | 0 / — |
Outcome results
Primary
Height Velocity Standard Deviation Score (SDS) at 12-Month Endpoint
Height velocity (difference between 2 height measurements, divided by years elapsed between measurements) SDS was derived by subtracting age and gender-matched population mean height velocity from patient's height velocity (based on measurements 12 months apart) then dividing this value by age and gender-matched population height velocity SD.
Time frame: 12-Months
Population: All enrolled participants with baseline and 12-month height measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose Somatropin | Height Velocity Standard Deviation Score (SDS) at 12-Month Endpoint | 1.83 standard deviation score | Standard Deviation 0.91 |
| Label Dose Somatropin | Height Velocity Standard Deviation Score (SDS) at 12-Month Endpoint | 1.38 standard deviation score | Standard Deviation 1.41 |
p-value: 0.3495% CI: [-0.5, 1.4]ANOVA
Secondary
Change From Baseline to 12-Month and 24-Month Endpoints in Height Standard Deviation Score (SDS)
This was derived by subtracting the age-and-gender-matched population 50th percentile height from the patient's height and then dividing this value by the age-and-gender-matched population height SD.
Time frame: Baseline, 12-Months, 24-Months
Population: All enrolled participants with at least one post-baseline height measurement, using last observation available prior to 12-month and 24-month visits respectively, if 12-month or 24-month height was not available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose Somatropin | Change From Baseline to 12-Month and 24-Month Endpoints in Height Standard Deviation Score (SDS) | 12-Month Height SDS Change (N=14, N=12) | 0.49 standard deviation score | Standard Error 0.12 |
| High Dose Somatropin | Change From Baseline to 12-Month and 24-Month Endpoints in Height Standard Deviation Score (SDS) | 24-Month Height SDS Change (N=13, N=11) | 0.88 standard deviation score | Standard Error 0.17 |
| Label Dose Somatropin | Change From Baseline to 12-Month and 24-Month Endpoints in Height Standard Deviation Score (SDS) | 12-Month Height SDS Change (N=14, N=12) | 0.34 standard deviation score | Standard Error 0.13 |
| Label Dose Somatropin | Change From Baseline to 12-Month and 24-Month Endpoints in Height Standard Deviation Score (SDS) | 24-Month Height SDS Change (N=13, N=11) | 0.40 standard deviation score | Standard Error 0.18 |
p-value: 0.38895% CI: [-0.21, 0.53]ANOVA
p-value: 0.06195% CI: [-0.02, 0.99]ANOVA
Secondary
Height Velocity Standard Deviation Score (SDS) at 24 Month Endpoint
Height velocity (difference between 2 height measurements, divided by years elapsed between measurements) SDS was derived by subtracting age and gender-matched population mean height velocity from patient's height velocity (based on measurements 12 months apart) then dividing this value by age and gender-matched population height velocity SD.
Time frame: 24 Months
Population: All enrolled participants with at least one post-baseline height velocity measurement, using the last observation available prior to the 24-month visit if the 24-month height velocity was not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose Somatropin | Height Velocity Standard Deviation Score (SDS) at 24 Month Endpoint | 2.58 standard deviation score | Standard Deviation 1.86 |
| Label Dose Somatropin | Height Velocity Standard Deviation Score (SDS) at 24 Month Endpoint | 1.45 standard deviation score | Standard Deviation 1.06 |
p-value: 0.08895% CI: [-0.18, 2.44]ANOVA