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

fliGHt: A Multicenter, Phase 3, Open-Label, 26-Week Trial Investigating the Safety, Tolerability and Efficacy of TransCon hGH Administered Once Weekly in Children With GHD

A 26 week trial of TransCon hGH, a long-acting growth hormone product, administered once-a-week. Approximately 150 children (males and females) with growth hormone deficiency (GHD) will be included. All study participants will receive TransCon hGH. This is a global trial that will be conducted in, but not limited to, the United States, Canada, Australia, and New Zealand.

Study Overview

• Status: Completed
• Conditions: Endocrine System Diseases; Pituitary Diseases; Hormone Deficiency; Growth Hormone Deficiency, Pediatric
• Intervention / Treatment: Drug: TransCon hGH

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Children's Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Stollery Children's Hospital
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1023
      • The Liggins Institute, The University of Auckland
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University Of Alabama
  • California
    • Los Angeles, California, United States, 90048
      • Neufeld Medical Group Inc.
    • Sacramento, California, United States, 95821
      • Center Of Excellence in Diabetes and Endocrinology
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Rocky Mountain Pediatric Endocrinology
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Health System
    • Orlando, Florida, United States, 32806
      • Orlando Health Inc.
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Children's Minnesota
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
    • Portland, Oregon, United States, 97227
      • Children's Diabetes and Endocrine Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Children's Hospital
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Investigator-determined GHD diagnosis prior to the historical initiation of daily hGH therapy.

2. 6 months to 17 years old, inclusive, at Visit 1

   1. If 3 to 17 years old, are taking daily hGH at a dose of ≥ 0.20 mg hGH/kg/week for at least 13 weeks but no more than 130 weeks prior to Visit 1
   2. If ≥ 6 months but < 3 years old, are either hGH treatment-naïve or are taking daily hGH at a dose of ≥ 0.20mg hGH/kg/week for no more than 130 weeks prior to Visit 1
3. Tanner stage < 5 at Visit 1
4. Open epiphyses (bone age ≤14.0 years for females or ≤16.0 years for males)
5. Written, signed, informed consent of the parent or legal guardian of the subject and written assent of the subject as required by the IRB/HREC/IEC

Exclusion Criteria:

1. Weight of < 5.5 kg or > 80 kg at Visit 1
2. Females of child-bearing potential
3. History of malignant disease
4. Any clinically significant abnormality likely to affect growth or the ability to evaluate growth (eg, chronic diseases or conditions such as renal insufficiency, spinal cord irradiation, hypothyroidism, active celiac disease, malnutrition or psychosocial dwarfism)
5. Poorly-controlled diabetes mellitus (HbA1c >8.0%) or diabetic complications
6. Known neutralizing antibodies against hGH
7. Major medical conditions, unless approved by Medical Monitor
8. Pregnancy
9. Presence of contraindications to hGH treatment
10. Likely to be non-compliant with respect to trial conduct (in regards to the subject and/or the parent/legal guardian/caregiver)
11. Participation in any other trial of an investigational agent within 30 days prior to Visit 1
12. Prior exposure to investigational hGH

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TransCon hGH; Once weekly subcutaneous injection of TransCon hGH	Drug: TransCon hGH; Once weekly subcutaneous injection at a starting dose of 0.24 mg/kg/week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]	Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment	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.	26 weeks
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	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.	26 weeks
Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment	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.	Baseline and 26 weeks
Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation	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.	26 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2017
• Primary Completion (Actual): March 19, 2019
• Study Completion (Actual): March 19, 2019

Study Registration Dates

• First Submitted: October 4, 2017
• First Submitted That Met QC Criteria: October 6, 2017
• First Posted (Actual): October 9, 2017

Study Record Updates

• Last Update Posted (Actual): January 4, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Growth Hormone Deficiency; Prodrug; Human Growth Hormone; hGH; GHD; Pediatric Growth Hormone Deficiency; Long Acting Growth Hormone; Somatropin; Growth Failure; Growth Hormone Replacement Therapy; Sustained Release Growth Hormone; rhGH; TransCon GH
• 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-302; U1111-1199-8218 (Other Identifier: WHO UTN)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No