Endocrine System Diseases, Growth Hormone Deficiency, Pediatric, hGH (Human Growth Hormone), Hormones, Pituitary Diseases
Conditions
Keywords
Human Growth Hormone, hGH, GHD, rHGH, Pediatric Growth Hormone Deficiency, Long Acting Growth Hormone, Somatropin, Prodrug, Growth Failure, Growth Hormone Replacement Therapy, Sustained Release, Sustained Release Growth Hormone, Growth Hormone Deficiency
Brief summary
A 52 week trial of TransCon hGH, a long-acting growth hormone product, versus human growth hormone therapy. TransCon hGH will be given once-a-week, human growth hormone (hGH) will be given daily. Approximately 150 prepubertal, hGH-treatment naïve children (males and females) with GHD will be included. Randomization will occur in a 2:1 ratio (TransCon hGH : Genotropin). This is a global trial that will be conducted in Armenia, Australia, Belarus, Bulgaria, Georgia, Greece, Italy, New Zealand, Poland, Romania, Russia, Turkey, Ukraine, and the United States.
Interventions
DRUGOnce weekly subcutaneous injection of TransCon hGH
Once weekly subcutaneous injection
DRUGOnce daily subcutaneous injection of Genotropin
Once daily subcutaneous injection
Sponsors
Ascendis Pharma Endocrinology Division A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Prepubertal children with GHD (either isolated or as part of a multiple pituitary hormone deficiency) in Tanner stage 1 (Tanner 1982) aged: * Boys: 3-12 years, inclusive * Girls: 3-11 years, inclusive * Impaired height (HT) defined as at least 2.0 standard deviations (SD) below the mean height for chronological age and sex (HT SDS ≤ -2.0) according to the 2000 CDC Growth Charts for the United States Methods and Development, available at http://www.cdc.gov/growthcharts/ * Diagnosis of GHD confirmed by 2 different GH stimulation tests, defined as a peak GH level of ≤10 ng/mL, determined with a validated assay * Bone age (BA) at least 6 months less than chronological age * Baseline IGF-1 level of at least 1 SD below the mean IGF-1 level standardized for age and sex (IGF-1 SDS ≤-1) * Written, signed informed consent of the parent(s) or legal guardian(s) of the subject and written assent of the subject (if the subject is able to read, understand, and sign)
Exclusion criteria
* Children with a body weight below 12 kg * Prior exposure to recombinant hGH or IGF-1 therapy * Children with past or present intracranial tumor growth as confirmed by a sellar MRI scan (with contrast) at Screening (MRI results from up to 6 months prior to Screening may be accepted) * Children with psychosocial dwarfism * Children with idiopathic short stature * History or presence of malignant disease; any evidence of present tumor growth * Closed epiphyses * Major medical conditions and/or presence of contraindication to hGH treatment * Participation in any other trial of an investigational agent within 3 months prior to Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Height Velocity at 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | 52 weeks | Annualized height velocity (AHV) at 52 weeks for weekly lonapegsomatropin (TransCon hGH) and daily hGH treatment groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | 52 Weeks | Number of participants with Treatment-Emergent Adverse Events for the weekly lonapegsomatropin and daily hGH treatment groups |
| Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 5, Week 13, Week 26, Week 39 and Week 52 | Annualized height velocity (AHV) over 52 weeks for weekly lonapegsomatropin and daily hGH treatment groups. AHV by visit was determined by ANCOVA model with multiple imputation. For each imputed data set, an ANCOVA model with by visit AHV as the dependent variable, treatment and gender as factors, baseline age, baseline peak GH levels (log transformed) at stimulation test, and baseline height SDS - average parental height SDS as covariates were fitted. |
| Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 5, Week 13, Week 26, Week 39 and Week 52 | Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)\^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height Standard Deviation Score (SDS) indicates a better outcome. The change from baseline in height SDS by visit was determined by ANCOVA model and included baseline age, peak GH levels (log transformed) at stimulation test and baseline height SDS as covariates, as well as treatment and gender as factors. |
| Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 13, Week 26, Week 39, and Week 52 | IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)\^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean. Average IGF-1 SDS by visit was determined by ANCOVA. The ANCOVA model included baseline age, peak GH levels (log transformed) at stimulation test, baseline IGF-1 SDS as covariates, as well as treatment and gender as factors. Modeled values begin at Week 13 corresponding with achievement of IGF-1 steady state. Average IGF-1 SDS values by visit for the Lonapegsomatropin group were derived from a population pharmacodynamic model; the average IGF-1 SDS values for the Genotropin group are represented by observed values. |
| Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation | Start of study treatment through Week 52 | Number of participants with treatment emergent anti-hGH binding antibody formation during the 52 week study. All samples were negative for anti-hGH neutralizing antibodies. |
Countries
Armenia, Australia, Belarus, Bulgaria, Georgia, Greece, Italy, New Zealand, Poland, Romania, Russia, Turkey (Türkiye), Ukraine, United States
Contacts
STUDY_DIRECTORStudy Director, MD
Ascendis Pharma A/S
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lonapegsomatropin Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) | 105 |
| Daily hGH Once daily subcutaneous injection of Genotropin | 56 |
| Total | 161 |
Baseline characteristics
| Characteristic | Lonapegsomatropin | Daily hGH | Total |
|---|---|---|---|
| Age, Continuous | 8.5 years STANDARD_DEVIATION 2.7 | 8.5 years STANDARD_DEVIATION 2.8 | 8.5 years STANDARD_DEVIATION 2.7 |
| Age, Customized Age, Categorical <6 years | 25 Participants | 14 Participants | 39 Participants |
| Age, Customized Age, Categorical ≥6 years | 80 Participants | 42 Participants | 122 Participants |
| BMI SDS | -0.32 standard deviation score STANDARD_DEVIATION 0.95 | -0.14 standard deviation score STANDARD_DEVIATION 1.07 | -0.25 standard deviation score STANDARD_DEVIATION 0.99 |
| Body Mass Index (BMI) | 16.06 kg/m^2 STANDARD_DEVIATION 1.78 | 16.46 kg/m^2 STANDARD_DEVIATION 2.17 | 16.20 kg/m^2 STANDARD_DEVIATION 1.93 |
| Height | 112.93 cm STANDARD_DEVIATION 14.09 | 112.15 cm STANDARD_DEVIATION 15.29 | 112.66 cm STANDARD_DEVIATION 14.48 |
| Height SDS | -2.89 standard deviation score STANDARD_DEVIATION 0.85 | -3.00 standard deviation score STANDARD_DEVIATION 0.9 | -2.93 standard deviation score STANDARD_DEVIATION 0.87 |
| IGF-1 SDS | -2.08 standard deviation score STANDARD_DEVIATION 0.88 | -1.96 standard deviation score STANDARD_DEVIATION 0.98 | -2.04 standard deviation score STANDARD_DEVIATION 0.92 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 100 Participants | 54 Participants | 154 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Race White | 100 Participants | 52 Participants | 152 Participants |
| Sex: Female, Male Female | 19 Participants | 10 Participants | 29 Participants |
| Sex: Female, Male Male | 86 Participants | 46 Participants | 132 Participants |
| Weight | 21.01 kg STANDARD_DEVIATION 6.54 | 21.20 kg STANDARD_DEVIATION 6.67 | 21.08 kg STANDARD_DEVIATION 6.56 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 56 |
| other Total, other adverse events | 81 / 105 | 39 / 56 |
| serious Total, serious adverse events | 1 / 105 | 1 / 56 |
Outcome results
Primary
Annualized Height Velocity at 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups
Annualized height velocity (AHV) at 52 weeks for weekly lonapegsomatropin (TransCon hGH) and daily hGH treatment groups
Time frame: 52 weeks
Population: The Intention-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of active treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lonapegsomatropin | Annualized Height Velocity at 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | 11.17 cm/year | Standard Error 0.23 |
| Daily hGH | Annualized Height Velocity at 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | 10.31 cm/year | Standard Error 0.3 |
Comparison: ANCOVA model with multiple imputation. For each imputed data set, an ANCOVA model with by visit AHV as the dependent variable; treatment and gender as factors; and baseline age, baseline peak GH levels (log transformed) at stimulation test, and baseline height SDS - average parental height SDS as covariates were fitted.p-value: 0.0088ANCOVA with multiple imputation
Secondary
Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups
Annualized height velocity (AHV) over 52 weeks for weekly lonapegsomatropin and daily hGH treatment groups. AHV by visit was determined by ANCOVA model with multiple imputation. For each imputed data set, an ANCOVA model with by visit AHV as the dependent variable, treatment and gender as factors, baseline age, baseline peak GH levels (log transformed) at stimulation test, and baseline height SDS - average parental height SDS as covariates were fitted.
Time frame: Week 5, Week 13, Week 26, Week 39 and Week 52
Population: The Intention-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of active treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Lonapegsomatropin | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 13 | 13.28 cm/year | Standard Error 0.49 |
| Lonapegsomatropin | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 39 | 11.89 cm/year | Standard Error 0.26 |
| Lonapegsomatropin | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 26 | 12.65 cm/year | Standard Error 0.32 |
| Lonapegsomatropin | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 52 | 11.17 cm/year | Standard Error 0.23 |
| Lonapegsomatropin | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 5 | 13.54 cm/year | Standard Error 1.07 |
| Daily hGH | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 52 | 10.31 cm/year | Standard Error 0.3 |
| Daily hGH | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 5 | 12.83 cm/year | Standard Error 1.37 |
| Daily hGH | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 13 | 12.22 cm/year | Standard Error 0.63 |
| Daily hGH | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 26 | 11.21 cm/year | Standard Error 0.42 |
| Daily hGH | Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 39 | 10.90 cm/year | Standard Error 0.33 |
Secondary
Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups
IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)\^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean. Average IGF-1 SDS by visit was determined by ANCOVA. The ANCOVA model included baseline age, peak GH levels (log transformed) at stimulation test, baseline IGF-1 SDS as covariates, as well as treatment and gender as factors. Modeled values begin at Week 13 corresponding with achievement of IGF-1 steady state. Average IGF-1 SDS values by visit for the Lonapegsomatropin group were derived from a population pharmacodynamic model; the average IGF-1 SDS values for the Genotropin group are represented by observed values.
Time frame: Week 13, Week 26, Week 39, and Week 52
Population: The Intention-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of active treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Lonapegsomatropin | Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 13 | 0.31 standard deviation score | Standard Error 0.09 |
| Lonapegsomatropin | Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 26 | 0.46 standard deviation score | Standard Error 0.08 |
| Lonapegsomatropin | Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 39 | 0.59 standard deviation score | Standard Error 0.09 |
| Lonapegsomatropin | Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 52 | 0.72 standard deviation score | Standard Error 0.09 |
| Daily hGH | Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 52 | -0.02 standard deviation score | Standard Error 0.12 |
| Daily hGH | Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 13 | -0.60 standard deviation score | Standard Error 0.11 |
| Daily hGH | Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 39 | -0.30 standard deviation score | Standard Error 0.11 |
| Daily hGH | Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 26 | -0.51 standard deviation score | Standard Error 0.1 |
Secondary
Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups
Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)\^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height Standard Deviation Score (SDS) indicates a better outcome. The change from baseline in height SDS by visit was determined by ANCOVA model and included baseline age, peak GH levels (log transformed) at stimulation test and baseline height SDS as covariates, as well as treatment and gender as factors.
Time frame: Week 5, Week 13, Week 26, Week 39 and Week 52
Population: The Intention-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of active treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Lonapegsomatropin | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 13 | 0.38 standard deviation score | Standard Error 0.02 |
| Lonapegsomatropin | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 39 | 0.92 standard deviation score | Standard Error 0.03 |
| Lonapegsomatropin | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 26 | 0.68 standard deviation score | Standard Error 0.03 |
| Lonapegsomatropin | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 52 | 1.10 standard deviation score | Standard Error 0.04 |
| Lonapegsomatropin | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 5 | 0.13 standard deviation score | Standard Error 0.02 |
| Daily hGH | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 52 | 0.96 standard deviation score | Standard Error 0.05 |
| Daily hGH | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 5 | 0.12 standard deviation score | Standard Error 0.02 |
| Daily hGH | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 13 | 0.33 standard deviation score | Standard Error 0.03 |
| Daily hGH | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 26 | 0.58 standard deviation score | Standard Error 0.04 |
| Daily hGH | Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups | Week 39 | 0.80 standard deviation score | Standard Error 0.04 |
Secondary
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
Number of participants with Treatment-Emergent Adverse Events for the weekly lonapegsomatropin and daily hGH treatment groups
Time frame: 52 Weeks
Population: The safety analysis population included all randomized subjects who had received at least 1 dose of active treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | TEAEs | 81 Participants |
| Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | TEAEs related to study drug | 12 Participants |
| Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | SAEs | 1 Participants |
| Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | SAEs related to study drug | 0 Participants |
| Daily hGH | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | SAEs related to study drug | 0 Participants |
| Daily hGH | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | TEAEs | 39 Participants |
| Daily hGH | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | SAEs | 1 Participants |
| Daily hGH | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | TEAEs related to study drug | 10 Participants |
Secondary
Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation
Number of participants with treatment emergent anti-hGH binding antibody formation during the 52 week study. All samples were negative for anti-hGH neutralizing antibodies.
Time frame: Start of study treatment through Week 52
Population: The safety analysis population included all randomized subjects who had received at least 1 dose of active treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lonapegsomatropin | Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation | 6 Participants |
| Daily hGH | Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation | 2 Participants |