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

Endocrine System Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03305016
• Other study ID #: TransCon hGH CT-302
• Secondary ID: U1111-1199-8218
• Status: Completed
• Phase: Phase 3
• Start date: November 13, 2017
• Est. completion date: March 19, 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: March 19, 2019
• Est. primary completion date: March 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency, Pediatric
• Hormone Deficiency
• Pituitary Diseases

Intervention

Drug:
• TransCon hGH
Once weekly subcutaneous injection at a starting dose of 0.24 mg/kg/week

Locations

Country	Name	City	State
Australia	Monash Children's Hospital	Clayton	Victoria
Canada	Stollery Children's Hospital	Edmonton	Alberta
New Zealand	The Liggins Institute, The University of Auckland	Grafton	Auckland
United States	University of Alabama	Birmingham	Alabama
United States	Rocky Mountain Pediatric Endocrinology	Centennial	Colorado
United States	University of Virginia Children's Hospital	Charlottesville	Virginia
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Children's Medical Center	Dallas	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Health System	Jacksonville	Florida
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Neufeld Medical Group Inc.	Los Angeles	California
United States	NYU Winthrop Hospital	Mineola	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Orlando Health Inc.	Orlando	Florida
United States	Children's Diabetes and Endocrine Center	Portland	Oregon
United States	Oregon Health & Science University	Portland	Oregon
United States	Center of Excellence in Diabetes and Endocrinology	Sacramento	California
United States	Children's Minnesota	Saint Paul	Minnesota
United States	Tallahassee Memorial Hospital	Tallahassee	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Ascendis Pharma Endocrinology Division A/S

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]	Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment	26 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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