A Phase 3 Trial of the Safety, Tolerability and Efficacy of TransCon hGH Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)
Primary Purpose
Growth Hormone Deficiency, Pediatric, hGH (Human Growth Hormone), Endocrine System Diseases
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Once weekly subcutaneous injection of TransCon hGH
Once daily subcutaneous injection of Genotropin
Sponsored by
About this trial
This is an interventional treatment trial for Growth Hormone Deficiency, Pediatric focused on measuring Human Growth Hormone, hGH, GHD, rHGH, Pediatric Growth Hormone Deficiency, Long Acting Growth Hormone, Somatropin, Prodrug, Growth Failure, Growth Hormone Replacement Therapy, Sustained Release, Sustained Release Growth Hormone, Growth Hormone Deficiency
Eligibility Criteria
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
Sites / Locations
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigatonal Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
- Ascendis Pharma Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
TransCon hGH
human growth hormone (Genotropin)
Arm Description
Once weekly subcutaneous injection of TransCon hGH
Once daily subcutaneous injection of Genotropin
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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.
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.
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.
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.
Full Information
NCT ID
NCT02781727
First Posted
May 19, 2016
Last Updated
December 6, 2021
Sponsor
Ascendis Pharma Endocrinology Division A/S
1. Study Identification
Unique Protocol Identification Number
NCT02781727
Brief Title
A Phase 3 Trial of the Safety, Tolerability and Efficacy of TransCon hGH Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
December 13, 2016 (Actual)
Primary Completion Date
January 17, 2019 (Actual)
Study Completion Date
January 17, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascendis Pharma Endocrinology Division A/S
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Growth Hormone Deficiency, Pediatric, hGH (Human Growth Hormone), Endocrine System Diseases, Hormones, Pituitary Diseases
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, Sustained Release Growth Hormone, Growth Hormone Deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
162 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TransCon hGH
Arm Type
Experimental
Arm Description
Once weekly subcutaneous injection of TransCon hGH
Arm Title
human growth hormone (Genotropin)
Arm Type
Active Comparator
Arm Description
Once daily subcutaneous injection of Genotropin
Intervention Type
Drug
Intervention Name(s)
Once weekly subcutaneous injection of TransCon hGH
Intervention Description
Once weekly subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Once daily subcutaneous injection of Genotropin
Intervention Description
Once daily subcutaneous injection
Primary Outcome Measure Information:
Title
Annualized Height Velocity at 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups
Description
Annualized height velocity (AHV) at 52 weeks for weekly lonapegsomatropin (TransCon hGH) and daily hGH treatment groups
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Number of participants with Treatment-Emergent Adverse Events for the weekly lonapegsomatropin and daily hGH treatment groups
Time Frame
52 Weeks
Title
Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups
Description
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.
Time Frame
Week 5, Week 13, Week 26, Week 39 and Week 52
Title
Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups
Description
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.
Time Frame
Week 5, Week 13, Week 26, Week 39 and Week 52
Title
Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups
Description
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.
Time Frame
Week 13, Week 26, Week 39, and Week 52
Title
Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation
Description
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.
Time Frame
Start of study treatment through Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Beckert, MD
Organizational Affiliation
Ascendis Pharma A/S
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Aimee D Shu, MD
Organizational Affiliation
Ascendis Pharma, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Ascendis Pharma Investigational Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Ascendis Pharma Investigational Site
City
Yerevan
ZIP/Postal Code
0075
Country
Armenia
Facility Name
Ascendis Pharma Investigational Site
City
Clayton
ZIP/Postal Code
3168
Country
Australia
Facility Name
Ascendis Pharma Investigational Site
City
Minsk
ZIP/Postal Code
220020
Country
Belarus
Facility Name
Ascendis Pharma Investigational Site
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
Facility Name
Ascendis Pharma Investigational Site
City
Tbilisi
ZIP/Postal Code
0144
Country
Georgia
Facility Name
Ascendis Pharma Investigational Site
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Ascendis Pharma Investigational Site
City
Tbilisi
ZIP/Postal Code
0162
Country
Georgia
Facility Name
Ascendis Pharma Investigational Site
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Ascendis Pharma Investigational Site
City
Milano
ZIP/Postal Code
20157
Country
Italy
Facility Name
Ascendis Pharma Investigational Site
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Ascendis Pharma Investigational Site
City
Grafton
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
Ascendis Pharma Investigatonal Site
City
Gdańsk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Ascendis Pharma Investigational Site
City
Warszawa
ZIP/Postal Code
02-691
Country
Poland
Facility Name
Ascendis Pharma Investigational Site
City
Iaşi
ZIP/Postal Code
700111
Country
Romania
Facility Name
Ascendis Pharma Investigational Site
City
Izhevsk
ZIP/Postal Code
426009
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Kazan
ZIP/Postal Code
420138
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Krasnoyarsk
ZIP/Postal Code
620022
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Moscow
ZIP/Postal Code
125373
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Moscow
ZIP/Postal Code
127994
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Nizhny Novgorod
ZIP/Postal Code
603136
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Novosibirsk
ZIP/Postal Code
630048
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Omsk
ZIP/Postal Code
644001
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Saint Petersburg
ZIP/Postal Code
191144
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Saint Petersburg
ZIP/Postal Code
194100
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Samara
ZIP/Postal Code
443079
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Saratov
ZIP/Postal Code
410054
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Tomsk
ZIP/Postal Code
634050
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Ufa
ZIP/Postal Code
450008
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Vologda
ZIP/Postal Code
160022
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
Voronezh
ZIP/Postal Code
394024
Country
Russian Federation
Facility Name
Ascendis Pharma Investigational Site
City
İzmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Ascendis Pharma Investigational Site
City
Melikgazi
ZIP/Postal Code
38039
Country
Turkey
Facility Name
Ascendis Pharma Investigational Site
City
Trabzon
ZIP/Postal Code
61080
Country
Turkey
Facility Name
Ascendis Pharma Investigational Site
City
Kharkov
ZIP/Postal Code
61093
Country
Ukraine
Facility Name
Ascendis Pharma Investigational Site
City
Kyiv
ZIP/Postal Code
01021
Country
Ukraine
Facility Name
Ascendis Pharma Investigational Site
City
Kyiv
ZIP/Postal Code
04114
Country
Ukraine
Facility Name
Ascendis Pharma Investigational Site
City
Odesa
ZIP/Postal Code
65031
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
34272849
Citation
Thornton PS, Maniatis AK, Aghajanova E, Chertok E, Vlachopapadopoulou E, Lin Z, Song W, Christoffersen ED, Breinholt VM, Kovalenko T, Giorgadze E, Korpal-Szczyrska M, Hofman PL, Karpf DB, Shu AD, Beckert M. Weekly Lonapegsomatropin in Treatment-Naive Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial. J Clin Endocrinol Metab. 2021 Oct 21;106(11):3184-3195. doi: 10.1210/clinem/dgab529.
Results Reference
derived
Learn more about this trial
A Phase 3 Trial of the Safety, Tolerability and Efficacy of TransCon hGH Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)
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