A Phase 3 Trial of the Safety, Tolerability and Efficacy of TransCon hGH Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)

Endocrine System Diseases Clinical Trial

Official title:

A Multicenter, Phase 3, Randomized, Open-label, Active-controlled, Parallel-group Trial Investigating the Safety, Tolerability, and Efficacy of TransCon hGH Administered Once a Week Versus Standard Daily hGH Replacement Therapy Over 52 Weeks in Prepubertal Children With Growth Hormone Deficiency (GHD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02781727
• Other study ID #: TransCon hGH CT-301
• Secondary ID: 2016-001145-11
• Status: Completed
• Phase: Phase 3
• Start date: December 13, 2016
• Est. completion date: January 17, 2019

Study information

• Verified date: December 2021
• Source: Ascendis Pharma A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A 52 week trial of TransCon hGH, a long-acting growth hormone product, versus human growth hormone therapy. TransCon hGH will be given once-a-week, human growth hormone (hGH) will be given daily. Approximately 150 prepubertal, hGH-treatment naïve children (males and females) with GHD will be included. Randomization will occur in a 2:1 ratio (TransCon hGH : Genotropin). This is a global trial that will be conducted in Armenia, Australia, Belarus, Bulgaria, Georgia, Greece, Italy, New Zealand, Poland, Romania, Russia, Turkey, Ukraine, and the United States.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: January 17, 2019
• Est. primary completion date: January 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 12 Years

Eligibility

Inclusion Criteria:

• Prepubertal children with GHD (either isolated or as part of a multiple pituitary

hormone deficiency) in Tanner stage 1 (Tanner 1982) aged:

• Boys: 3-12 years, inclusive
• Girls: 3-11 years, inclusive
• Impaired height (HT) defined as at least 2.0 standard deviations (SD) below the mean height for chronological age and sex (HT SDS = -2.0) according to the 2000 CDC Growth Charts for the United States Methods and Development, available at http://www.cdc.gov/growthcharts/
• Diagnosis of GHD confirmed by 2 different GH stimulation tests, defined as a peak GH level of =10 ng/mL, determined with a validated assay
• Bone age (BA) at least 6 months less than chronological age
• Baseline IGF-1 level of at least 1 SD below the mean IGF-1 level standardized for age and sex (IGF-1 SDS =-1)
• Written, signed informed consent of the parent(s) or legal guardian(s) of the subject and written assent of the subject (if the subject is able to read, understand, and sign)

Exclusion Criteria:

• Children with a body weight below 12 kg
• Prior exposure to recombinant hGH or IGF-1 therapy
• Children with past or present intracranial tumor growth as confirmed by a sellar MRI scan (with contrast) at Screening (MRI results from up to 6 months prior to Screening may be accepted)
• Children with psychosocial dwarfism
• Children with idiopathic short stature
• History or presence of malignant disease; any evidence of present tumor growth
• Closed epiphyses
• Major medical conditions and/or presence of contraindication to hGH treatment
• Participation in any other trial of an investigational agent within 3 months prior to Screening

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency, Pediatric
• hGH (Human Growth Hormone)
• Hormones
• Pituitary Diseases

Intervention

Drug:
• Once weekly subcutaneous injection of TransCon hGH
Once weekly subcutaneous injection
• Once daily subcutaneous injection of Genotropin
Once daily subcutaneous injection

Locations

Country	Name	City	State
Armenia	Ascendis Pharma Investigational Site	Yerevan
Australia	Ascendis Pharma Investigational Site	Clayton
Belarus	Ascendis Pharma Investigational Site	Minsk
Bulgaria	Ascendis Pharma Investigational Site	Varna
Georgia	Ascendis Pharma Investigational Site	Tbilisi
Georgia	Ascendis Pharma Investigational Site	Tbilisi
Georgia	Ascendis Pharma Investigational Site	Tbilisi
Greece	Ascendis Pharma Investigational Site	Athens
Italy	Ascendis Pharma Investigational Site	Milano
Italy	Ascendis Pharma Investigational Site	Roma
New Zealand	Ascendis Pharma Investigational Site	Grafton
Poland	Ascendis Pharma Investigatonal Site	Gdansk
Poland	Ascendis Pharma Investigational Site	Warszawa
Romania	Ascendis Pharma Investigational Site	Iasi
Russian Federation	Ascendis Pharma Investigational Site	Izhevsk
Russian Federation	Ascendis Pharma Investigational Site	Kazan
Russian Federation	Ascendis Pharma Investigational Site	Krasnoyarsk
Russian Federation	Ascendis Pharma Investigational Site	Moscow
Russian Federation	Ascendis Pharma Investigational Site	Moscow
Russian Federation	Ascendis Pharma Investigational Site	Nizhny Novgorod
Russian Federation	Ascendis Pharma Investigational Site	Novosibirsk
Russian Federation	Ascendis Pharma Investigational Site	Omsk
Russian Federation	Ascendis Pharma Investigational Site	Saint Petersburg
Russian Federation	Ascendis Pharma Investigational Site	Saint Petersburg
Russian Federation	Ascendis Pharma Investigational Site	Samara
Russian Federation	Ascendis Pharma Investigational Site	Saratov
Russian Federation	Ascendis Pharma Investigational Site	Tomsk
Russian Federation	Ascendis Pharma Investigational Site	Ufa
Russian Federation	Ascendis Pharma Investigational Site	Vologda
Russian Federation	Ascendis Pharma Investigational Site	Voronezh
Turkey	Ascendis Pharma Investigational Site	Izmir
Turkey	Ascendis Pharma Investigational Site	Melikgazi
Turkey	Ascendis Pharma Investigational Site	Trabzon
Ukraine	Ascendis Pharma Investigational Site	Kharkov
Ukraine	Ascendis Pharma Investigational Site	Kyiv
Ukraine	Ascendis Pharma Investigational Site	Kyiv
Ukraine	Ascendis Pharma Investigational Site	Odesa
United States	Ascendis Pharma Investigational Site	Birmingham	Alabama
United States	Ascendis Pharma Investigational Site	Centennial	Colorado
United States	Ascendis Pharma Investigational Site	Dallas	Texas
United States	Ascendis Pharma Investigational Site	Fort Worth	Texas
United States	Ascendis Pharma Investigational Site	Jackson	Mississippi
United States	Ascendis Pharma Investigational Site	Jacksonville	Florida
United States	Ascendis Pharma Investigational Site	Lebanon	New Hampshire
United States	Ascendis Pharma Investigational Site	Little Rock	Arkansas
United States	Ascendis Pharma Investigational Site	Los Angeles	California
United States	Ascendis Pharma Investigational Site	Mineola	New York
United States	Ascendis Pharma Investigational Site	Oklahoma City	Oklahoma
United States	Ascendis Pharma Investigational Site	Orange	California
United States	Ascendis Pharma Investigational Site	Orlando	Florida
United States	Ascendis Pharma Investigational Site	Portland	Oregon
United States	Ascendis Pharma Investigational Site	Saint Paul	Minnesota
United States	Ascendis Pharma Investigational Site	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Ascendis Pharma Endocrinology Division A/S

Countries where clinical trial is conducted

United States,  Armenia,  Australia,  Belarus,  Bulgaria,  Georgia,  Greece,  Italy,  New Zealand,  Poland,  Romania,  Russian Federation,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Height Velocity at 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups	Annualized height velocity (AHV) at 52 weeks for weekly lonapegsomatropin (TransCon hGH) and daily hGH treatment groups	52 weeks
Secondary	Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]	Number of participants with Treatment-Emergent Adverse Events for the weekly lonapegsomatropin and daily hGH treatment groups	52 Weeks
Secondary	Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups	Annualized height velocity (AHV) over 52 weeks for weekly lonapegsomatropin and daily hGH treatment groups. AHV by visit was determined by ANCOVA model with multiple imputation. For each imputed data set, an ANCOVA model with by visit AHV as the dependent variable, treatment and gender as factors, baseline age, baseline peak GH levels (log transformed) at stimulation test, and baseline height SDS - average parental height SDS as covariates were fitted.	Week 5, Week 13, Week 26, Week 39 and Week 52
Secondary	Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups	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 Standard Deviation Score (SDS) indicates a better outcome. The change from baseline in height SDS by visit was determined by ANCOVA model and included baseline age, peak GH levels (log transformed) at stimulation test and baseline height SDS as covariates, as well as treatment and gender as factors.	Week 5, Week 13, Week 26, Week 39 and Week 52
Secondary	Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups	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. Average IGF-1 SDS by visit was determined by ANCOVA. The ANCOVA model included baseline age, peak GH levels (log transformed) at stimulation test, baseline IGF-1 SDS as covariates, as well as treatment and gender as factors. Modeled values begin at Week 13 corresponding with achievement of IGF-1 steady state. Average IGF-1 SDS values by visit for the Lonapegsomatropin group were derived from a population pharmacodynamic model; the average IGF-1 SDS values for the Genotropin group are represented by observed values.	Week 13, Week 26, Week 39, and Week 52
Secondary	Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation	Number of participants with treatment emergent anti-hGH binding antibody formation during the 52 week study. All samples were negative for anti-hGH neutralizing antibodies.	Start of study treatment through Week 52