Long-Acting Growth Hormone in Children Compared to Daily rhGH (VELOCITY)

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

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

Study Overview

• Status: Completed
• Conditions: Growth Disorders
• Intervention / Treatment: Drug: Somavaratan; Drug: rhGH

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Versartis Inc.
• Investigators: Study Director: Will Charlton, MD, Sponsor GmbH

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2015
• Primary Completion (Actual): August 23, 2017
• Study Completion (Actual): August 23, 2017

Study Registration Dates

• First Submitted: January 7, 2015
• First Submitted That Met QC Criteria: January 14, 2015
• First Posted (Estimate): January 15, 2015

Study Record Updates

• Last Update Posted (Actual): December 30, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Growth Hormone Deficiency; Human Growth Hormone; Pediatric Growth Hormone Deficiency; Long Acting Growth Hormone; Growth Hormone Replacement Therapy; VRS-317; Versartis; somavaratan; growth failure; Long Acting Recombinant Growth Hormone; Xten
• Additional Relevant MeSH Terms: Pathologic Processes; Growth Disorders; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 14VR4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No