Clinical trial NCT02781727: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Ascendis Pharma A/S
Sponsor class: INDUSTRY
First posted: 2016-05-24
Enrollment: 162
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Annualized Height Velocity at 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups
timeFrame: 52 weeks
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 52 Weeks
measure: Annualized Height Velocity Over 52 Weeks for Weekly Lonapegsomatropin and Daily hGH Treatment Groups
timeFrame: Week 5, Week 13, Week 26, Week 39 and Week 52
measure: Change in Height Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups
timeFrame: Week 5, Week 13, Week 26, Week 39 and Week 52
measure: Average IGF-1 Standard Deviation Score Over 52 Weeks for the Weekly Lonapegsomatropin and Daily hGH Treatment Groups
timeFrame: Week 13, Week 26, Week 39, and Week 52
measure: Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation
timeFrame: Start of study treatment through Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Ascendis Pharma Investigational Site
state: Alabama
city: Little Rock
country: United States
facility: Ascendis Pharma Investigational Site
state: Arkansas
city: Los Angeles
country: United States
facility: Ascendis Pharma Investigational Site
state: California
city: Orange
country: United States
facility: Ascendis Pharma Investigational Site
state: California
city: Centennial
country: United States
facility: Ascendis Pharma Investigational Site
state: Colorado
city: Jacksonville
country: United States
facility: Ascendis Pharma Investigational Site
state: Florida
city: Orlando
country: United States
facility: Ascendis Pharma Investigational Site
state: Florida
city: Saint Paul
country: United States
facility: Ascendis Pharma Investigational Site
state: Minnesota
city: Jackson
country: United States
facility: Ascendis Pharma Investigational Site
state: Mississippi
city: Lebanon
country: United States
facility: Ascendis Pharma Investigational Site
state: New Hampshire
city: Mineola
country: United States
facility: Ascendis Pharma Investigational Site
state: New York
city: Oklahoma City
country: United States
facility: Ascendis Pharma Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: Ascendis Pharma Investigational Site
state: Oregon
city: Dallas
country: United States
facility: Ascendis Pharma Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Ascendis Pharma Investigational Site
state: Texas
city: Tacoma
country: United States
facility: Ascendis Pharma Investigational Site
state: Washington
city: Yerevan
country: Armenia
facility: Ascendis Pharma Investigational Site
city: Clayton
country: Australia
facility: Ascendis Pharma Investigational Site
city: Minsk
country: Belarus
facility: Ascendis Pharma Investigational Site
city: Varna
country: Bulgaria
facility: Ascendis Pharma Investigational Site
city: Tbilisi
country: Georgia
facility: Ascendis Pharma Investigational Site
city: Tbilisi
country: Georgia
facility: Ascendis Pharma Investigational Site
city: Tbilisi
country: Georgia
facility: Ascendis Pharma Investigational Site
city: Athens
country: Greece
facility: Ascendis Pharma Investigational Site
city: Milano
country: Italy
facility: Ascendis Pharma Investigational Site
city: Roma
country: Italy
facility: Ascendis Pharma Investigational Site
city: Grafton
country: New Zealand
facility: Ascendis Pharma Investigational Site
city: Gdańsk
country: Poland
facility: Ascendis Pharma Investigatonal Site
city: Warszawa
country: Poland
facility: Ascendis Pharma Investigational Site
city: Iaşi
country: Romania
facility: Ascendis Pharma Investigational Site
city: Izhevsk
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Kazan
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Krasnoyarsk
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Moscow
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Moscow
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Nizhny Novgorod
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Omsk
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Samara
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Saratov
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Tomsk
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Ufa
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Vologda
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: Voronezh
country: Russian Federation
facility: Ascendis Pharma Investigational Site
city: İzmir
country: Turkey
facility: Ascendis Pharma Investigational Site
city: Melikgazi
country: Turkey
facility: Ascendis Pharma Investigational Site
city: Trabzon
country: Turkey
facility: Ascendis Pharma Investigational Site
city: Kharkov
country: Ukraine
facility: Ascendis Pharma Investigational Site
city: Kyiv
country: Ukraine
facility: Ascendis Pharma Investigational Site
city: Kyiv
country: Ukraine
facility: Ascendis Pharma Investigational Site
city: Odesa
country: Ukraine
facility: Ascendis Pharma Investigational Site
Study officials:
affiliation: Ascendis Pharma A/S
name: Michael Beckert, MD
role: STUDY_DIRECTOR
affiliation: Ascendis Pharma, Inc.
name: Aimee D Shu, MD
role: STUDY_DIRECTOR
References:
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.