Trial Outcomes & Findings for A Long-Term Trial Investigating Safety and Efficacy of TransCon hGH in Children With Growth Hormone Deficiency Who Have Completed a Prior TransCon hGH Clinical Trial (NCT NCT03344458)

NCT ID: NCT03344458

Last Updated: 2024-05-08

Results Overview

Long-term safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 298 participants
• Primary outcome timeframe: Up to Week 208
• Results posted on: 2024-05-08

Participant Flow

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.

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.

Participant milestones

Measure	Lonapegsomatropin Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH)
Overall Study STARTED	298
Overall Study COMPLETED	259
Overall Study NOT COMPLETED	39

Reasons for withdrawal

Measure	Lonapegsomatropin Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH)
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	16
Overall Study Other reasons	10
Overall Study Lost to Follow-up	9
Overall Study Protocol Violation	3

Baseline Characteristics

A Long-Term Trial Investigating Safety and Efficacy of TransCon hGH in Children With Growth Hormone Deficiency Who Have Completed a Prior TransCon hGH Clinical Trial

Baseline characteristics by cohort

Measure	Lonapegsomatropin n=298 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH)
Age, Continuous	10.27 years STANDARD_DEVIATION 3.421 • n=5 Participants
Age, Customized Infants and toddlers (28 days-23 months)	1 Participants n=5 Participants
Age, Customized Children (2-11 years)	196 Participants n=5 Participants
Age, Customized Adolescents (12-17 years)	101 Participants n=5 Participants
Sex: Female, Male Female	63 Participants n=5 Participants
Sex: Female, Male Male	235 Participants n=5 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	2 Participants n=5 Participants
Race/Ethnicity, Customized White	270 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	3 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	3 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	15 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	272 Participants n=5 Participants
Race/Ethnicity, Customized Not reported	8 Participants n=5 Participants
Region of Enrollment Armenia	10 Participants n=5 Participants
Region of Enrollment Greece	3 Participants n=5 Participants
Region of Enrollment New Zealand	9 Participants n=5 Participants
Region of Enrollment United States	174 Participants n=5 Participants
Region of Enrollment Ukraine	11 Participants n=5 Participants
Region of Enrollment Poland	8 Participants n=5 Participants
Region of Enrollment Georgia	10 Participants n=5 Participants
Region of Enrollment Australia	5 Participants n=5 Participants
Region of Enrollment Belarus	5 Participants n=5 Participants
Region of Enrollment Bulgaria	3 Participants n=5 Participants
Region of Enrollment Russia	50 Participants n=5 Participants
Region of Enrollment Canada	1 Participants n=5 Participants
Region of Enrollment Turkey	3 Participants n=5 Participants
Region of Enrollment Italy	3 Participants n=5 Participants
Region of Enrollment Romania	3 Participants n=5 Participants
Tanner Stage Tanner Stage 1	214 Participants n=5 Participants
Tanner Stage Tanner Stage 2	40 Participants n=5 Participants
Tanner Stage Tanner Stage 3	25 Participants n=5 Participants
Tanner Stage Tanner Stage 4	16 Participants n=5 Participants
Tanner Stage Tanner Stage 5	3 Participants n=5 Participants
Height SDS	-1.564 Height Standard Deviation Score STANDARD_DEVIATION 0.878 • n=5 Participants
IGF-1 SDS	0.515 IGF-1 Standard Deviation Score STANDARD_DEVIATION 1.579 • n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 208

Long-term safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment

Outcome measures

Measure	Lonapegsomatropin n=298 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH)
Number of Subjects With Treatment-Emergent Adverse Events [Long-Term Safety and Tolerability]	226 Participants

SECONDARY outcome

Timeframe: 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.

Annualized height velocity (AHV) by visit with long-term dosing of weekly lonapegsomatropin treatment

Outcome measures

Measure	Lonapegsomatropin n=298 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH)
Annualized Height Velocity by Visit Week 13	8.904 cm/year Standard Deviation 2.795
Annualized Height Velocity by Visit Week 52	8.560 cm/year Standard Deviation 1.801
Annualized Height Velocity by Visit Week 104	7.854 cm/year Standard Deviation 1.953
Annualized Height Velocity by Visit Week 156	7.081 cm/year Standard Deviation 1.838
Annualized Height Velocity by Visit Week 208	6.462 cm/year Standard Deviation 1.868

SECONDARY outcome

Timeframe: Up to Week 208

Population: At each post-baseline visit, n is the number of subjects with non-missing baseline and specific post-baseline.

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.

Outcome measures

Measure	Lonapegsomatropin n=298 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH)
IGF-1 SDS by Visit Week 13	1.210 Standard Deviation Score Standard Deviation 1.400
IGF-1 SDS by Visit Week 52	1.355 Standard Deviation Score Standard Deviation 1.231
IGF-1 SDS by Visit Week 104	1.613 Standard Deviation Score Standard Deviation 1.189
IGF-1 SDS by Visit Week 156	1.453 Standard Deviation Score Standard Deviation 1.125
IGF-1 SDS by Visit Week 208	1.597 Standard Deviation Score Standard Deviation 1.177

SECONDARY outcome

Timeframe: Up to Week 208

Population: At each post-baseline visit, n is the number of subjects with non-missing baseline and specific post-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.

Outcome measures

Measure	Lonapegsomatropin n=298 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH)
Height SDS - Change From Baseline Week 13	0.141 Standard Deviation Score Standard Deviation 0.125
Height SDS - Change From Baseline Week 52	0.491 Standard Deviation Score Standard Deviation 0.307
Height SDS - Change From Baseline Week 104	0.841 Standard Deviation Score Standard Deviation 0.487
Height SDS - Change From Baseline Week 156	1.089 Standard Deviation Score Standard Deviation 0.534
Height SDS - Change From Baseline Week 208	1.242 Standard Deviation Score Standard Deviation 0.652

Adverse Events

Lonapegsomatropin

Serious events: 21 serious events

Other events: 225 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lonapegsomatropin n=298 participants at risk Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH)
Infections and infestations Abscess	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Gastroenteritis	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Injury, poisoning and procedural complications Femur fracture	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Injury, poisoning and procedural complications Forearm fracture	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Injury, poisoning and procedural complications Humerus fracture	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Injury, poisoning and procedural complications Limb injury	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Injury, poisoning and procedural complications Lip injury	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Injury, poisoning and procedural complications Upper limb fracture	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Congenital, familial and genetic disorders Diverticulitis Meckel's	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Nervous system disorders Brain stem infarction	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Nervous system disorders Epilepsy	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Nervous system disorders Generalised tonic-clonic seizure	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Nervous system disorders Headache	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
General disorders Pyrexia	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Immune system disorders Serum sickness-like reaction	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Gastrointestinal disorders Cyclic vomiting syndrome	0.34% 1/298 • Number of events 6 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Gastrointestinal disorders Inguinal hernia	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Gastrointestinal disorders Vomiting	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Renal and urinary disorders Nephrotic syndrome	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Musculoskeletal and connective tissue disorders Scoliosis	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations COVID-19	1.0% 3/298 • Number of events 3 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Pneumonia	0.67% 2/298 • Number of events 2 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Gastroenteritis salmonella	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Gastrointestinal viral infection	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Sinusitis	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Tonsillitis	0.34% 1/298 • Number of events 1 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.

Other adverse events

Measure	Lonapegsomatropin n=298 participants at risk Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH)
Investigations SARS-CoV-2 test positive	5.7% 17/298 • Number of events 17 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Nervous system disorders Headache	11.7% 35/298 • Number of events 73 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
General disorders Pyrexia	12.4% 37/298 • Number of events 56 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Immune system disorders Seasonal allergy	6.4% 19/298 • Number of events 24 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Gastrointestinal disorders Vomiting	8.1% 24/298 • Number of events 33 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Respiratory, thoracic and mediastinal disorders Cough	9.4% 28/298 • Number of events 52 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Upper respiratory tract infection	21.8% 65/298 • Number of events 164 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations COVID-19	13.4% 40/298 • Number of events 41 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Nasopharyngitis	13.4% 40/298 • Number of events 68 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Influenza	10.1% 30/298 • Number of events 36 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Pharyngitis streptococcal	9.1% 27/298 • Number of events 46 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Respiratory tract infection viral	7.4% 22/298 • Number of events 48 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Ear infection	6.0% 18/298 • Number of events 30 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Gastroenteritis	5.7% 17/298 • Number of events 22 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Bronchitis	5.0% 15/298 • Number of events 23 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.
Infections and infestations Viral upper respiratory tract infection	5.0% 15/298 • Number of events 16 • From Informed Consent Form signature up to 14 days after the final dose, up to 260 weeks. A treatment-emergent adverse event (TEAE) was defined as any adverse event that first occurred or worsened after the first trial drug dose and before the end of the trial. Each subject was counted only once within each preferred term.

Additional Information

Aimee D. Shu, MD

Ascendis Pharma, Inc.

Phone: +1 650 352 8389

Email: ads@ascendispharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place