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

Phase 3

Completed

• Conditions: Growth Hormone Deficiency, Pediatric; Pituitary Diseases; Endocrine System Diseases; Hormone Deficiency
• Interventions: Drug: TransCon hGH

• Registration Number: NCT03305016
• Lead Sponsor: Ascendis Pharma Endocrinology Division A/S

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-10-04
• Study First Submitted QC: 2017-10-06
• Study First Posted: 2017-10-09
• Study Start: 2017-11-13
• Primary Completion: 2019-03-19
• Study Completion: 2019-03-19
• Disposition First Submitted: 2020-02-18
• Results First Submitted: 2021-09-24
• Status Verified: 2021-12
• Results First Submitted QC: 2021-12-07
• Disposition First Submitted QC: 2021-12-07
• Last Update Submitted: 2021-12-07
• Results First Posted: 2022-01-04
• Disposition First Posted: 2022-01-04
• Last Update Posted: 2022-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 146

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TransCon hGH	TransCon hGH	Once weekly subcutaneous injection of TransCon hGH

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (24)

Neufeld Medical Group Inc.; 🇺🇸 Los Angeles, California, United States

Tallahassee Memorial Hospital; 🇺🇸 Tallahassee, Florida, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Stollery Children's Hospital; 🇨🇦 Edmonton, Alberta, Canada

Dartmouth Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

Cook Children's Medical Center; 🇺🇸 Fort Worth, Texas, United States

Children's Minnesota; 🇺🇸 Saint Paul, Minnesota, United States

Nemours Children's Health System; 🇺🇸 Jacksonville, Florida, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

University of Virginia Children's Hospital; 🇺🇸 Charlottesville, Virginia, United States

NYU Winthrop Hospital; 🇺🇸 Mineola, New York, United States

Monash Children's Hospital; 🇦🇺 Clayton, Victoria, Australia

The Liggins Institute, The University of Auckland; 🇳🇿 Grafton, Auckland, New Zealand

Children's Medical Center; 🇺🇸 Dallas, Texas, United States

Rocky Mountain Pediatric Endocrinology; 🇺🇸 Centennial, Colorado, United States

Children's Hospital of The King's Daughters; 🇺🇸 Norfolk, Virginia, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Center of Excellence in Diabetes and Endocrinology; 🇺🇸 Sacramento, California, United States

Orlando Health Inc.; 🇺🇸 Orlando, Florida, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Children's Diabetes and Endocrine Center; 🇺🇸 Portland, Oregon, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States