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

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)

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.

Study Overview

• Status: Completed
• Conditions: Endocrine System Diseases; Pituitary Diseases; Hormones; Growth Hormone Deficiency, Pediatric; hGH (Human Growth Hormone)
• Intervention / Treatment: Drug: Once weekly subcutaneous injection of TransCon hGH; Drug: Once daily subcutaneous injection of Genotropin

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 3

Contacts and Locations

Study Locations

• Armenia
  • Yerevan, Armenia, 0075
    • Ascendis Pharma Investigational Site
• Australia
  • Clayton, Australia, 3168
    • Ascendis Pharma Investigational Site
• Belarus
  • Minsk, Belarus, 220020
    • Ascendis Pharma Investigational Site
• Bulgaria
  • Varna, Bulgaria, 9010
    • Ascendis Pharma Investigational Site
• Georgia
  • Tbilisi, Georgia, 0144
    • Ascendis Pharma Investigational Site
  • Tbilisi, Georgia, 0159
    • Ascendis Pharma Investigational Site
  • Tbilisi, Georgia, 0162
    • Ascendis Pharma Investigational Site
• Greece
  • Athens, Greece, 11527
    • Ascendis Pharma Investigational Site
• Italy
  • Milano, Italy, 20157
    • Ascendis Pharma Investigational Site
  • Roma, Italy, 00165
    • Ascendis Pharma Investigational Site
• New Zealand
  • Grafton, New Zealand, 1023
    • Ascendis Pharma Investigational Site
• Poland
  • Gdańsk, Poland, 80-952
    • Ascendis Pharma Investigatonal Site
  • Warszawa, Poland, 02-691
    • Ascendis Pharma Investigational Site
• Romania
  • Iaşi, Romania, 700111
    • Ascendis Pharma Investigational Site
• Russian Federation
  • Izhevsk, Russian Federation, 426009
    • Ascendis Pharma Investigational Site
  • Kazan, Russian Federation, 420138
    • Ascendis Pharma Investigational Site
  • Krasnoyarsk, Russian Federation, 620022
    • Ascendis Pharma Investigational Site
  • Moscow, Russian Federation, 125373
    • Ascendis Pharma Investigational Site
  • Moscow, Russian Federation, 127994
    • Ascendis Pharma Investigational Site
  • Nizhny Novgorod, Russian Federation, 603136
    • Ascendis Pharma Investigational Site
  • Novosibirsk, Russian Federation, 630048
    • Ascendis Pharma Investigational Site
  • Omsk, Russian Federation, 644001
    • Ascendis Pharma Investigational Site
  • Saint Petersburg, Russian Federation, 191144
    • Ascendis Pharma Investigational Site
  • Saint Petersburg, Russian Federation, 194100
    • Ascendis Pharma Investigational Site
  • Samara, Russian Federation, 443079
    • Ascendis Pharma Investigational Site
  • Saratov, Russian Federation, 410054
    • Ascendis Pharma Investigational Site
  • Tomsk, Russian Federation, 634050
    • Ascendis Pharma Investigational Site
  • Ufa, Russian Federation, 450008
    • Ascendis Pharma Investigational Site
  • Vologda, Russian Federation, 160022
    • Ascendis Pharma Investigational Site
  • Voronezh, Russian Federation, 394024
    • Ascendis Pharma Investigational Site
• Turkey
  • Melikgazi, Turkey, 38039
    • Ascendis Pharma Investigational Site
  • Trabzon, Turkey, 61080
    • Ascendis Pharma Investigational Site
  • İzmir, Turkey, 35100
    • Ascendis Pharma Investigational Site
• Ukraine
  • Kharkov, Ukraine, 61093
    • Ascendis Pharma Investigational Site
  • Kyiv, Ukraine, 01021
    • Ascendis Pharma Investigational Site
  • Kyiv, Ukraine, 04114
    • Ascendis Pharma Investigational Site
  • Odesa, Ukraine, 65031
    • Ascendis Pharma Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Ascendis Pharma Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Ascendis Pharma Investigational Site
  • California
    • Los Angeles, California, United States, 90048
      • Ascendis Pharma Investigational Site
    • Orange, California, United States, 92868
      • Ascendis Pharma Investigational Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Ascendis Pharma Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Ascendis Pharma Investigational Site
    • Orlando, Florida, United States, 32806
      • Ascendis Pharma Investigational Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Ascendis Pharma Investigational Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Ascendis Pharma Investigational Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Ascendis Pharma Investigational Site
  • New York
    • Mineola, New York, United States, 11501
      • Ascendis Pharma Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Ascendis Pharma Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Ascendis Pharma Investigational Site
  • Texas
    • Dallas, Texas, United States, 75235
      • Ascendis Pharma Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Ascendis Pharma Investigational Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Ascendis Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TransCon hGH; Once weekly subcutaneous injection of TransCon hGH	Drug: Once weekly subcutaneous injection of TransCon hGH; Once weekly subcutaneous injection
Active Comparator: human growth hormone (Genotropin); Once daily subcutaneous injection of Genotropin	Drug: Once daily subcutaneous injection of Genotropin; Once daily subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Ascendis Pharma Endocrinology Division A/S
• Investigators: Study Director: Michael Beckert, MD, Ascendis Pharma A/S; Study Director: Aimee D Shu, MD, Ascendis Pharma, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2016
• Primary Completion (Actual): January 17, 2019
• Study Completion (Actual): January 17, 2019

Study Registration Dates

• First Submitted: May 19, 2016
• First Submitted That Met QC Criteria: May 20, 2016
• First Posted (Estimate): May 24, 2016

Study Record Updates

• Last Update Posted (Actual): January 4, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Growth Hormone Deficiency; Prodrug; Sustained Release; Human Growth Hormone; hGH; GHD; rHGH; Pediatric Growth Hormone Deficiency; Long Acting Growth Hormone; Somatropin; Growth Failure; Growth Hormone Replacement Therapy; Sustained Release Growth Hormone
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Pituitary Diseases; Dwarfism, Pituitary; Endocrine System Diseases
• Other Study ID Numbers: TransCon hGH CT-301; 2016-001145-11 (EudraCT Number)