Endocrine System Diseases, Growth Hormone Deficiency, Pediatric, Hormone Deficiency, 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 Growth Hormone, Growth Hormone Deficiency, TransCon GH
Brief summary
A 26 week trial of TransCon hGH, a long-acting growth hormone product, administered once-a-week. Approximately 150 children (males and females) with growth hormone deficiency (GHD) will be included. All study participants will receive TransCon hGH. This is a global trial that will be conducted in, but not limited to, the United States, Canada, Australia, and New Zealand.
Interventions
DRUGTransCon hGH
Once weekly subcutaneous injection at a starting dose of 0.24 mg/kg/week
Sponsors
Ascendis Pharma Endocrinology Division A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All study participants will receive TransCon hGH
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Investigator-determined GHD diagnosis prior to the historical initiation of daily hGH therapy. 2. 6 months to 17 years old, inclusive, at Visit 1 1. If 3 to 17 years old, are taking daily hGH at a dose of ≥ 0.20 mg hGH/kg/week for at least 13 weeks but no more than 130 weeks prior to Visit 1 2. If ≥ 6 months but \< 3 years old, are either hGH treatment-naïve or are taking daily hGH at a dose of ≥ 0.20mg hGH/kg/week for no more than 130 weeks prior to Visit 1 3. Tanner stage \< 5 at Visit 1 4. Open epiphyses (bone age ≤14.0 years for females or ≤16.0 years for males) 5. Written, signed, informed consent of the parent or legal guardian of the subject and written assent of the subject as required by the IRB/HREC/IEC
Exclusion criteria
1. Weight of \< 5.5 kg or \> 80 kg at Visit 1 2. Females of child-bearing potential 3. History of malignant disease 4. Any clinically significant abnormality likely to affect growth or the ability to evaluate growth (eg, chronic diseases or conditions such as renal insufficiency, spinal cord irradiation, hypothyroidism, active celiac disease, malnutrition or psychosocial dwarfism) 5. Poorly-controlled diabetes mellitus (HbA1c \>8.0%) or diabetic complications 6. Known neutralizing antibodies against hGH 7. Major medical conditions, unless approved by Medical Monitor 8. Pregnancy 9. Presence of contraindications to hGH treatment 10. Likely to be non-compliant with respect to trial conduct (in regards to the subject and/or the parent/legal guardian/caregiver) 11. Participation in any other trial of an investigational agent within 30 days prior to Visit 1 12. Prior exposure to investigational hGH
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | 26 weeks | Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment | 26 weeks | Annualized height velocity (AHV) at 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. The AHV at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model. |
| Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment | 26 weeks | 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. |
| Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment | Baseline and 26 weeks | 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 SDS indicates a better outcome. The height SDS change from baseline at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model. |
| Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation | 26 weeks | Number of participants with treatment emergent anti-hGH antibodies over 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. All samples were negative for anti-hGH neutralizing antibodies. |
Countries
Australia, Canada, New Zealand, United States
Contacts
STUDY_DIRECTORAimee Shu, MD
Ascendis Pharma, Inc.
Participant flow
Pre-assignment details
A total of 162 subjects were screened for entry into this trial; of these, 16 subjects did not meet eligibility criteria and were considered screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Lonapegsomatropin Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week | 146 |
| Total | 146 |
Baseline characteristics
| Characteristic | Lonapegsomatropin |
|---|---|
| Age, Continuous | 10.6 years STANDARD_DEVIATION 3.9 |
| Age, Customized Age, Categorical: ≥11 years (girls) or ≥12 years (boys) | 67 Participants |
| Age, Customized Age, Categorical: ≥3 and <6 years | 20 Participants |
| Age, Customized Age, Categorical: <3 years | 4 Participants |
| Age, Customized Age, Categorical: ≥6 to <11 years (girls) or ≥6 to <12 years (boys) | 55 Participants |
| Body Mass Index (BMI) | 17.5 kg/m^2 STANDARD_DEVIATION 3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants |
| Height | 132.4 cm STANDARD_DEVIATION 22.5 |
| Height SDS | -1.42 standard deviation score STANDARD_DEVIATION 0.84 |
| IGF-1 SDS | 0.85 standard deviation score STANDARD_DEVIATION 1.29 |
| Race/Ethnicity, Customized Race Asian | 6 Participants |
| Race/Ethnicity, Customized Race Black or African American | 3 Participants |
| Race/Ethnicity, Customized Race More than one race | 2 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Race Unknown | 9 Participants |
| Race/Ethnicity, Customized Race White | 124 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 110 Participants |
| Weight | 32.3 kg STANDARD_DEVIATION 14.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 146 |
| other Total, other adverse events | 65 / 146 |
| serious Total, serious adverse events | 1 / 146 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment
Time frame: 26 weeks
Population: The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | TEAE | 83 Participants |
| Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | Related TEAE | 6 Participants |
| Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | Serious TEAE | 1 Participants |
| Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | Related Serious TEAE | 0 Participants |
Secondary
Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment
Annualized height velocity (AHV) at 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. The AHV at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.
Time frame: 26 weeks
Population: The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lonapegsomatropin | Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment | 8.72 cm/year | Standard Error 0.24 |
Secondary
Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment
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 SDS indicates a better outcome. The height SDS change from baseline at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.
Time frame: Baseline and 26 weeks
Population: The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lonapegsomatropin | Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment | 0.25 standard deviation score | Standard Error 0.02 |
Secondary
Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation
Number of participants with treatment emergent anti-hGH antibodies over 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. All samples were negative for anti-hGH neutralizing antibodies.
Time frame: 26 weeks
Population: The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lonapegsomatropin | Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation | 4 Participants |
Secondary
Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment
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.
Time frame: 26 weeks
Population: The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lonapegsomatropin | Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment | 74 Participants |