Long-Acting Growth Hormone in Children Compared to Daily rhGH

Study Overview
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Brief Summary
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The trial will compare a twice-monthly somavaratan dosing regimen for non-inferiority of treatment effect against daily injections of rhGH.

Detailed Description
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This study is designed as a pivotal study to compare the safety and efficacy of a selected dose regimen of somavaratan to daily rhGH. The study is a randomized, multi-center, open label study of 12 months duration. The primary endpoint is height velocity at 12 months.

Official Title
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Comparison of Somavaratan (VRS-317), a Long-acting Human Growth Hormone, to Daily rhGH in a Phase 3, Randomized, One-year, Open-label, Multi-center, Non-inferiority Trial in Pre-pubertal Children With Growth Hormone Deficiency

Conditions
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Growth Disorders

Intervention / Treatment
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* Drug: Somavaratan
* Drug: rhGH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronological Age ≥ 3.0 years and ≤ 10.0 (girls) and ≤ 11.0 (boys). Pre-pubertal status: Absent breast development in girls, testicular volume < 4.0 mL in boys. Diagnosis of growth hormone deficiency (GHD) as documented by two or more growth hormone (GH) stimulation test results ≤ 10.0 ng/mL. Height standard deviation score (SDS) ≤ -2.0 at screening. Weight for Stature ≥ 10th percentile. Insulin-like growth factor-I (IGF-I) SDS ≤ -1.0 at screening. Delayed bone age (≥ 6 months). Exclusion Criteria: Prior treatment with any growth promoting agent History of, or concurrent significant disease (for example, diabetes, cystic fibrosis, renal insufficiency). Chromosomal aneuploidy, significant gene mutations (other than those that cause GHD) or confirmed diagnosis of a named syndrome. A diagnosis of Attention Deficit Hyperactivity Disorder. Daily use of anti-inflammatory doses of glucocorticoid. Prior history of leukemia, lymphoma, sarcoma or cancer. Treatment with an investigational drug in the 30 days prior to screening. Known allergy to constituents of the study drug formulation. Ocular findings suggestive of increased intracranial pressure and/or retinopathy at screening. Significant spinal abnormalities including scoliosis, kyphosis and spina bifida variants. Significant abnormality in screening laboratory studies

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 11 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Somavaratan<br>Participants will receive somavaratan 3.5 milligrams (mg)/kilogram (kg) subcutaneous (SC) bolus injection twice monthly for 12 months. | Drug: Somavaratan<br>* Somavaratan will be administered per dose and schedule specified in the arm description.<br>* Other names: VRS-317;|
| Active Comparator: rhGH<br>Participants will receive commercially available rhGH (genotropin) 34 micrograms (μg)/kg once daily SC bolus injection for 12 months. | Drug: rhGH<br>* rhGH will be administered per dose and schedule specified in the arm description.<br>* Other names: recombinant growth hormone therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Height Velocity | Height measured without shoes in triplicate by stadiometer. Annual height velocity was calculated as (height at Month 12 - height at Baseline)/(Month 12 Date - Baseline Date) * 365.25, where height was expressed as centimeters (cm) so that height velocity is expressed as centimeters per year (cm/yr). Annual height velocity after 12 months continuous treatment with either somavaratan or daily rhGH has been reported. Missing data was imputed using last observation carried forward. Least square (LS) mean was calculated using analysis of covariance (ANCOVA) model. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Height Standard Deviation Score (SDS) at Month 12 | Height SDS was determined using the Center for Disease Control (CDC) Clinical Growth Charts; 2000. The SD score was calculated as the participant's height value minus the mean divided by the standard deviation (SD). The mean and the SD vary depending on the age and sex of the participant. Mean change from baseline in height SDS at Month 12 is presented. | Baseline, Month 12 | 
| Change From Baseline in Bone Age Relative to Chronological Age at Month 12, as Assessed by Central Reader | Bone age was assessed from a radiograph of the left hand and wrist by central reader. | Baseline, Month 12 | 
| Change From Baseline in Body Mass Index (BMI) at Month 12 | The BMI is a person's weight in kilograms (kg) divided by the square of height in meters. | Baseline, Month 12 | 
| Change From Baseline in Body Weight at Month 12 | Body weight measured in light clothing and without shoes. | Baseline, Month 12 | 
| Change From Baseline in Insulin-like Growth Factor 1 (IGF-I) SDS at Month 12 | The SD score was calculated as the actual value of IGF-I minus mean reference value of IGF-1 divided by reference standard deviation of IGF-I. The mean and the SD vary depending on the age and sex of the participant. Change in IGF-I level (SD score) at Month 12 from Baseline was assessed. A higher score reflects a better outcome. | Baseline, Month 12 | 
| Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) at Month 12 |  | Baseline, Month 12 | 
| Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. | Baseline up to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VRS-317, Growth Hormone Deficiency, Long Acting Recombinant Growth Hormone, Long Acting Growth Hormone, Pediatric Growth Hormone Deficiency, Growth Hormone Replacement Therapy, Versartis, Xten, Human Growth Hormone, somavaratan, growth failure