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 multicenter, phase 3, long-term extension trial of TransCon hGH administered once-weekly in children with growth hormone deficiency (GHD) who previously participated in a phase 3 TransCon hGH trial. Approximately 300 children (males and females) with 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, Poland, Bulgaria, Ukraine, Armenia, Russia and Australia.
Interventions
DRUGTransCon hGH
Once weekly subcutaneous injection of TransCon hGH
Sponsors
Ascendis Pharma 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
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Children who have completed a prior phase 3 TransCon hGH trial 2. Children who have not permanently discontinued study drug in the prior trial 3. 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. Poorly-controlled diabetes mellitus (HbA1c ≥ 8.0%) or diabetic complications 2. Evidence of closed epiphyses, defined as bone age \> 14.0 years for females or \> 16.0 years for males 3. Major medical conditions unless approved by Medical Expert 4. Known hypersensitivity to the components of the trial medication 5. Likely to be non-compliant with respect to trial conduct (in regards to the subject and/or the parent/legal guardian/caregiver) 6. Pregnancy 7. Any other reason that in the opinion of the investigator would prevent the subject from completing participation or following the trial schedule
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment-Emergent Adverse Events [Long-Term Safety and Tolerability] | Up to Week 208 | Long-term safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Height Velocity by Visit | Up to Week 208 | Annualized height velocity (AHV) by visit with long-term dosing of weekly lonapegsomatropin treatment |
| IGF-1 SDS by Visit | Up to Week 208 | Insulin-like Growth Factor-1 (IGF-1) standard deviation score (SDS) by visit with long-term dosing of weekly lonapegsomatropin treatment at Week 13, Week 52, Week 104, Week 156, and Week 208. IGF-1 SDS is the number of standard deviations above or below the mean IGF-1 level for a child of the same age and sex. The target range for IGF-1 SDS was 0 to +2. An IGF-1 SDS of 0 represents the population mean. If the IGF-1 SDS is \< 0, then the negative score indicates an IGF-1 below the mean IGF-1 for a child of the same age and sex. If the IGF-1 SDS is \> 0, then the positive score indicates an IGF-1 above the mean IGF-1 for a child of the same age and sex. A positive score of IGF-1 SDS indicates a better outcome. |
| Height SDS - Change From Baseline | Up to Week 208 | Change in Height Standard Deviation Score (SDS) from baseline with long-term dosing of weekly lonapegsomatropin treatment at Week 13, Week 52, Week 104, Week 156, and Week 208. Height SDS is the number of standard deviations above or below the mean height for age and sex. A Standard Deviation Score of 0 equals the population mean. If the Height SDS is \< 0, then the negative score indicates a height below the mean height for a child of the same age and sex. If the Height SDS is \> 0, then the positive score indicates a height above the mean height for a child of the same age and sex. A positive change from baseline in Height SDS indicates improved outcomes. |
Countries
Armenia, Australia, Belarus, Bulgaria, Georgia, Greece, New Zealand, Poland, Russia, Ukraine, United States
Contacts
STUDY_DIRECTORMedical Director, MD
Ascendis Pharma A/S
Participant flow
Recruitment details
Overall, 298 subjects entered the extension trial from the parent trials: 103 subjects from the CT-301 Lonapegsomatropin group, 55 subjects from the CT-301 Genotropin group, and 140 subjects from the CT-302 Lonapegsomatropin group.
Pre-assignment details
Patients who completed a prior phase 3 lonapegsomatropin trial were screened. Patients with poorly controlled diabetes or diabetic complications, or with evidence of closed epiphyses or known hypersensitivity to the trial medication were excluded. All inclusion/exclusion criteria were met during enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Lonapegsomatropin Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) | 298 |
| Total | 298 |
Baseline characteristics
| Characteristic | Lonapegsomatropin |
|---|---|
| Age, Continuous | 10.27 years STANDARD_DEVIATION 3.421 |
| Age, Customized Adolescents (12-17 years) | 101 Participants |
| Age, Customized Children (2-11 years) | 196 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 1 Participants |
| Height SDS | -1.564 Height Standard Deviation Score STANDARD_DEVIATION 0.878 |
| IGF-1 SDS | 0.515 IGF-1 Standard Deviation Score STANDARD_DEVIATION 1.579 |
| Race/Ethnicity, Customized Asian | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 15 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 272 Participants |
| Race/Ethnicity, Customized Not reported | 8 Participants |
| Race/Ethnicity, Customized Other | 4 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants |
| Race/Ethnicity, Customized White | 270 Participants |
| Region of Enrollment Armenia | 10 Participants |
| Region of Enrollment Australia | 5 Participants |
| Region of Enrollment Belarus | 5 Participants |
| Region of Enrollment Bulgaria | 3 Participants |
| Region of Enrollment Canada | 1 Participants |
| Region of Enrollment Georgia | 10 Participants |
| Region of Enrollment Greece | 3 Participants |
| Region of Enrollment Italy | 3 Participants |
| Region of Enrollment New Zealand | 9 Participants |
| Region of Enrollment Poland | 8 Participants |
| Region of Enrollment Romania | 3 Participants |
| Region of Enrollment Russia | 50 Participants |
| Region of Enrollment Turkey | 3 Participants |
| Region of Enrollment Ukraine | 11 Participants |
| Region of Enrollment United States | 174 Participants |
| Sex: Female, Male Female | 63 Participants |
| Sex: Female, Male Male | 235 Participants |
| Tanner Stage Tanner Stage 1 | 214 Participants |
| Tanner Stage Tanner Stage 2 | 40 Participants |
| Tanner Stage Tanner Stage 3 | 25 Participants |
| Tanner Stage Tanner Stage 4 | 16 Participants |
| Tanner Stage Tanner Stage 5 | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 298 |
| other Total, other adverse events | 225 / 298 |
| serious Total, serious adverse events | 21 / 298 |
Outcome results
Primary
Number of Subjects With Treatment-Emergent Adverse Events [Long-Term Safety and Tolerability]
Long-term safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment
Time frame: Up to Week 208
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lonapegsomatropin | Number of Subjects With Treatment-Emergent Adverse Events [Long-Term Safety and Tolerability] | 226 Participants |
Secondary
Annualized Height Velocity by Visit
Annualized height velocity (AHV) by visit with long-term dosing of weekly lonapegsomatropin treatment
Time frame: Up to Week 208
Population: A rolling baseline was used to ensure the baseline was no more than 52 weeks apart. The rolling baseline was used to calculate the annualized height velocity to ensure there was a one-year gap; from the 15-month (65 weeks) visit onwards, the baseline value used for each successive HV calculation was the patient's height at the visit 52 weeks previously. At each post-baseline visit, n is the number of subjects with non-missing baseline and a specific post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lonapegsomatropin | Annualized Height Velocity by Visit | Week 13 | 8.904 cm/year | Standard Deviation 2.795 |
| Lonapegsomatropin | Annualized Height Velocity by Visit | Week 52 | 8.560 cm/year | Standard Deviation 1.801 |
| Lonapegsomatropin | Annualized Height Velocity by Visit | Week 104 | 7.854 cm/year | Standard Deviation 1.953 |
| Lonapegsomatropin | Annualized Height Velocity by Visit | Week 156 | 7.081 cm/year | Standard Deviation 1.838 |
| Lonapegsomatropin | Annualized Height Velocity by Visit | Week 208 | 6.462 cm/year | Standard Deviation 1.868 |
Secondary
Height SDS - Change From Baseline
Change in Height Standard Deviation Score (SDS) from baseline with long-term dosing of weekly lonapegsomatropin treatment at Week 13, Week 52, Week 104, Week 156, and Week 208. Height SDS is the number of standard deviations above or below the mean height for age and sex. A Standard Deviation Score of 0 equals the population mean. If the Height SDS is \< 0, then the negative score indicates a height below the mean height for a child of the same age and sex. If the Height SDS is \> 0, then the positive score indicates a height above the mean height for a child of the same age and sex. A positive change from baseline in Height SDS indicates improved outcomes.
Time frame: Up to Week 208
Population: At each post-baseline visit, n is the number of subjects with non-missing baseline and specific post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lonapegsomatropin | Height SDS - Change From Baseline | Week 13 | 0.141 Standard Deviation Score | Standard Deviation 0.125 |
| Lonapegsomatropin | Height SDS - Change From Baseline | Week 52 | 0.491 Standard Deviation Score | Standard Deviation 0.307 |
| Lonapegsomatropin | Height SDS - Change From Baseline | Week 104 | 0.841 Standard Deviation Score | Standard Deviation 0.487 |
| Lonapegsomatropin | Height SDS - Change From Baseline | Week 156 | 1.089 Standard Deviation Score | Standard Deviation 0.534 |
| Lonapegsomatropin | Height SDS - Change From Baseline | Week 208 | 1.242 Standard Deviation Score | Standard Deviation 0.652 |
Secondary
IGF-1 SDS by Visit
Insulin-like Growth Factor-1 (IGF-1) standard deviation score (SDS) by visit with long-term dosing of weekly lonapegsomatropin treatment at Week 13, Week 52, Week 104, Week 156, and Week 208. IGF-1 SDS is the number of standard deviations above or below the mean IGF-1 level for a child of the same age and sex. The target range for IGF-1 SDS was 0 to +2. An IGF-1 SDS of 0 represents the population mean. If the IGF-1 SDS is \< 0, then the negative score indicates an IGF-1 below the mean IGF-1 for a child of the same age and sex. If the IGF-1 SDS is \> 0, then the positive score indicates an IGF-1 above the mean IGF-1 for a child of the same age and sex. A positive score of IGF-1 SDS indicates a better outcome.
Time frame: Up to Week 208
Population: At each post-baseline visit, n is the number of subjects with non-missing baseline and specific post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lonapegsomatropin | IGF-1 SDS by Visit | Week 13 | 1.210 Standard Deviation Score | Standard Deviation 1.4 |
| Lonapegsomatropin | IGF-1 SDS by Visit | Week 52 | 1.355 Standard Deviation Score | Standard Deviation 1.231 |
| Lonapegsomatropin | IGF-1 SDS by Visit | Week 104 | 1.613 Standard Deviation Score | Standard Deviation 1.189 |
| Lonapegsomatropin | IGF-1 SDS by Visit | Week 156 | 1.453 Standard Deviation Score | Standard Deviation 1.125 |
| Lonapegsomatropin | IGF-1 SDS by Visit | Week 208 | 1.597 Standard Deviation Score | Standard Deviation 1.177 |