Trial Outcomes & Findings for A Safety, Tolerability and Efficacy Study of TransCon hGH in Children With Growth Hormone Deficiency (NCT NCT03305016)

NCT ID: NCT03305016

Last Updated: 2022-01-04

Results Overview

Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 146 participants
• Primary outcome timeframe: 26 weeks
• Results posted on: 2022-01-04

Participant Flow

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.

Participant milestones

Measure	Lonapegsomatropin Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Overall Study STARTED	146
Overall Study COMPLETED	144
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Lonapegsomatropin Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Overall Study Withdrawal by Subject	2

Baseline Characteristics

A Safety, Tolerability and Efficacy Study of TransCon hGH in Children With Growth Hormone Deficiency

Baseline characteristics by cohort

Measure	Lonapegsomatropin n=146 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Age, Continuous	10.6 years STANDARD_DEVIATION 3.9 • n=5 Participants
Age, Customized Age, Categorical: · <3 years	4 Participants n=5 Participants
Age, Customized Age, Categorical: · ≥3 and <6 years	20 Participants n=5 Participants
Age, Customized Age, Categorical: · ≥6 to <11 years (girls) or ≥6 to <12 years (boys)	55 Participants n=5 Participants
Age, Customized Age, Categorical: · ≥11 years (girls) or ≥12 years (boys)	67 Participants n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants
Sex: Female, Male Male	110 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	124 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	12 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	6 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	124 Participants n=5 Participants
Race/Ethnicity, Customized Race · More than one race	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Unknown	9 Participants n=5 Participants
Height	132.4 cm STANDARD_DEVIATION 22.5 • n=5 Participants
Height SDS	-1.42 standard deviation score STANDARD_DEVIATION 0.84 • n=5 Participants
Weight	32.3 kg STANDARD_DEVIATION 14.2 • n=5 Participants
Body Mass Index (BMI)	17.5 kg/m^2 STANDARD_DEVIATION 3.0 • n=5 Participants
IGF-1 SDS	0.85 standard deviation score STANDARD_DEVIATION 1.29 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment

Outcome measures

Measure	Lonapegsomatropin n=146 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] TEAE	83 Participants
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Related TEAE	6 Participants
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Serious TEAE	1 Participants
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Related Serious TEAE	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Lonapegsomatropin n=144 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment	8.72 cm/year Standard Error 0.24

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Lonapegsomatropin n=142 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
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

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Lonapegsomatropin n=144 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment	0.25 standard deviation score Standard Error 0.02

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Lonapegsomatropin n=145 Participants Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation	4 Participants

Adverse Events

Lonapegsomatropin

Serious events: 1 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lonapegsomatropin n=146 participants at risk Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Cardiac disorders Atrioventricular block	0.68% 1/146 • Number of events 1 • 26 weeks
General disorders Chest pain	0.68% 1/146 • Number of events 1 • 26 weeks

Other adverse events

Measure	Lonapegsomatropin n=146 participants at risk Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
General disorders Pyrexia	11.6% 17/146 • 26 weeks
Infections and infestations Nasopharyngitis	9.6% 14/146 • 26 weeks
Infections and infestations Upper respiratory tract infection	9.6% 14/146 • 26 weeks
Nervous system disorders Headache	8.2% 12/146 • 26 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.5% 8/146 • 26 weeks

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