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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Growth Hormone Deficiency, Pediatric, Endocrine System Diseases, Hormone Deficiency, Pituitary Diseases

Intervention / Treatment
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* Drug: TransCon hGH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Investigator-determined GHD diagnosis prior to the historical initiation of daily hGH therapy. 6 months to 17 years old, inclusive, at Visit 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 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 Tanner stage < 5 at Visit 1 Open epiphyses (bone age ≤14.0 years for females or ≤16.0 years for males) 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: Weight of < 5.5 kg or > 80 kg at Visit 1 Females of child-bearing potential History of malignant disease 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) Poorly-controlled diabetes mellitus (HbA1c >8.0%) or diabetic complications Known neutralizing antibodies against hGH Major medical conditions, unless approved by Medical Monitor Pregnancy Presence of contraindications to hGH treatment Likely to be non-compliant with respect to trial conduct (in regards to the subject and/or the parent/legal guardian/caregiver) Participation in any other trial of an investigational agent within 30 days prior to Visit 1 Prior exposure to investigational hGH

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All study participants will receive TransCon hGH
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TransCon hGH<br>Once weekly subcutaneous injection of TransCon hGH | Drug: TransCon hGH<br>* Once weekly subcutaneous injection at a starting dose of 0.24 mg/kg/week<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Growth Hormone, hGH, GHD, rhGH, Pediatric Growth Hormone Deficiency, Long Acting Growth Hormone, Somatropin, Prodrug, Growth Failure, Growth Hormone Replacement Therapy, Sustained Release Growth Hormone, Growth Hormone Deficiency, TransCon GH