Adult Growth Hormone Deficiency, Endocrine System Diseases, Hormone Deficiency
Conditions
Keywords
Human Growth Hormone, hGH, rhGH, GHD, Adult Growth Hormone Deficiency, Long Acting Growth Hormone, Lonapegsomatropin, Prodrug, Growth Hormone Replacement Therapy, Sustained Release Growth Hormone, Growth Hormone Deficiency, TransCon hGH, Skytrofa
Brief summary
This was a phase 3 open-label multicenter extension study designed to evaluate the long-term safety and efficacy of Lonapegsomatropin administered once-weekly. The study participants were adults (males and females) with confirmed growth hormone deficiency (GHD) having completed the treatment period in study TCH-306 (foresiGHt; NCT04615273).
Interventions
Study participants were individually dosed with subcutaneous injection of Lonapegsomatropin once-weekly for 52 weeks.
Sponsors
Ascendis Pharma Endocrinology Division A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label treatment with weekly Lonapegsomatropin
Eligibility
Sex/Gender
ALL
Age
23 Years to 81 Years
Healthy volunteers
No
Inclusion criteria
* Signing of the trial specific informed consent * Completion of the treatment period and Visit 7 assessments of trial TCH-306, including collection and upload of Visit 7 dual-X-ray-absorptiometry (DXA) scan * Fundoscopy at Visit 7 in trial TCH-306 without signs/symptoms of intracranial hypertension or diabetic retinopathy stage 2 / moderate or above
Exclusion criteria
* Diabetes mellitus if any of the following were met: 1. Poorly controlled diabetes, defined as HbA1C higher than 7.5% according to central laboratory at Visit 7 in trial TCH-306 2. Use of diabetes mellitus drugs other than metformin and/or dipeptidyl peptidase-4 (DPP-4) inhibitors * Active malignant disease or history of malignancy. * Known history of hypersensitivity and/or idiosyncrasy to the investigational product (somatropin or excipients) * Female who was pregnant, plans to become pregnant, or was breastfeeding * Female participant of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) not willing throughout the trial to use contraceptives as required by local law or practice. Details included in Appendix 4/section 10.4 of the protocol * Male participant not willing throughout the trial to use contraceptives as required by local law or practice. Details included in Appendix 4/ section 10.4 of the protocol * Any disease or condition that, in the judgement of the investigator, may make the participant unlikely to comply with the requirements of the protocol or any condition that presents undue risk from the investigational product or trial procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | Up to 52 Weeks | An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. An AE was considered a TEAE if it occurred on or after the first dose of investigational product and was not present prior to the first dose, or it was present at the first dose but increased in severity during the trial. A serious AE was any untoward medical occurrence at any dose that met any of the following criteria: resulted in death; was life threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the trial drug or was considered a significant medical event by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trunk Percent Fat at Week 52 | Baseline main trial to week 52 (extension period) | Trunk percent fat was assessed by dual-energy X-ray absorptiometry. |
| Change From Baseline in Trunk Fat Mass at Week 52 | Baseline main trial to week 52 (extension period) | Trunk fat mass was assessed by dual-energy X-ray absorptiometry. |
| Change From Baseline in Total Body Lean Mass at Week 52 | Baseline main trial to week 52 (extension period) | Total body lean mass was assessed by dual-energy X-ray absorptiometry. |
Countries
Armenia, Australia, Canada, France, Georgia, Germany, Greece, Israel, Italy, Japan, Malaysia, Poland, Romania, Serbia, Slovakia, South Korea, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Director, MD
Ascendis Pharma A/S
Participant flow
Pre-assignment details
The study TCH-306 EXT enrolled participants who had completed treatment in TCH-306 (NCT04615273) study. In Japan only, participants switched from commercially available somatropin therapy (results reported separately).
Participants by arm
| Arm | Count |
|---|---|
| Lonapegsomatropin/Lonapegsomatropin Participants who had completed treatment with lonapegsomatropin in TCH-306 study were enrolled in the extension study and received lonapegsomatropin administered once weekly by subcutaneous injection for a treatment period of up to 52 weeks. | 73 |
| Placebo/Lonapegsomatropin Participants who had completed treatment with placebo in TCH-306 study were enrolled in the extension study and received lonapegsomatropin administered once weekly by subcutaneous injection for a treatment period of up to 52 weeks. | 73 |
| Somatropin/Lonapegsomatropin Participants who had completed treatment with somatropin in TCH-306 study were enrolled in the extension study and received lonapegsomatropin administered once weekly by subcutaneous injection for a treatment period of up to 52 weeks. | 74 |
| Total | 220 |
Baseline characteristics
| Characteristic | Lonapegsomatropin/Lonapegsomatropin | Placebo/Lonapegsomatropin | Somatropin/Lonapegsomatropin | Total |
|---|---|---|---|---|
| Age, Customized >= 30 to <= 60 years | 53 Participants | 51 Participants | 52 Participants | 156 Participants |
| Age, Customized < 30 years | 10 Participants | 13 Participants | 14 Participants | 37 Participants |
| Age, Customized > 60 years | 10 Participants | 9 Participants | 8 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants | 69 Participants | 67 Participants | 204 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 7 Participants | 8 Participants | 24 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 3 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 59 Participants | 62 Participants | 64 Participants | 185 Participants |
| Sex: Female, Male Female | 37 Participants | 32 Participants | 31 Participants | 100 Participants |
| Sex: Female, Male Male | 36 Participants | 41 Participants | 43 Participants | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 73 | 0 / 73 | 0 / 74 |
| other Total, other adverse events | 25 / 73 | 29 / 73 | 21 / 74 |
| serious Total, serious adverse events | 7 / 73 | 4 / 73 | 5 / 74 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation
An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. An AE was considered a TEAE if it occurred on or after the first dose of investigational product and was not present prior to the first dose, or it was present at the first dose but increased in severity during the trial. A serious AE was any untoward medical occurrence at any dose that met any of the following criteria: resulted in death; was life threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the trial drug or was considered a significant medical event by the investigator.
Time frame: Up to 52 Weeks
Population: Analysis was performed on all participants who were exposed to any amount of the trial drug in the study TCH-306 EXT.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lonapegsomatropin/Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | Serious TEAEs | 7 Participants |
| Lonapegsomatropin/Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | TEAEs | 48 Participants |
| Lonapegsomatropin/Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 2 Participants |
| Placebo/Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | Serious TEAEs | 4 Participants |
| Placebo/Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | TEAEs | 52 Participants |
| Placebo/Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 4 Participants |
| Somatropin/Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | TEAEs | 45 Participants |
| Somatropin/Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 2 Participants |
| Somatropin/Lonapegsomatropin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation | Serious TEAEs | 5 Participants |
Secondary
Change From Baseline in Total Body Lean Mass at Week 52
Total body lean mass was assessed by dual-energy X-ray absorptiometry.
Time frame: Baseline main trial to week 52 (extension period)
Population: Analysis was performed on safety analysis set. Here, Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Lonapegsomatropin/Lonapegsomatropin | Change From Baseline in Total Body Lean Mass at Week 52 | 2.26 kilograms |
| Placebo/Lonapegsomatropin | Change From Baseline in Total Body Lean Mass at Week 52 | 1.97 kilograms |
| Somatropin/Lonapegsomatropin | Change From Baseline in Total Body Lean Mass at Week 52 | 2.07 kilograms |
Secondary
Change From Baseline in Trunk Fat Mass at Week 52
Trunk fat mass was assessed by dual-energy X-ray absorptiometry.
Time frame: Baseline main trial to week 52 (extension period)
Population: Analysis was performed on safety analysis set. Here, Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Lonapegsomatropin/Lonapegsomatropin | Change From Baseline in Trunk Fat Mass at Week 52 | 0.15 kilograms |
| Placebo/Lonapegsomatropin | Change From Baseline in Trunk Fat Mass at Week 52 | -0.16 kilograms |
| Somatropin/Lonapegsomatropin | Change From Baseline in Trunk Fat Mass at Week 52 | -0.00 kilograms |
Secondary
Change From Baseline in Trunk Percent Fat at Week 52
Trunk percent fat was assessed by dual-energy X-ray absorptiometry.
Time frame: Baseline main trial to week 52 (extension period)
Population: Analysis was performed on safety analysis set. Here, Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Lonapegsomatropin/Lonapegsomatropin | Change From Baseline in Trunk Percent Fat at Week 52 | -1.21 percent fat |
| Placebo/Lonapegsomatropin | Change From Baseline in Trunk Percent Fat at Week 52 | -1.60 percent fat |
| Somatropin/Lonapegsomatropin | Change From Baseline in Trunk Percent Fat at Week 52 | -1.11 percent fat |