Long-Acting Growth Hormone in Children Compared to Daily rhGH (VELOCITY)
Primary Purpose
Growth Disorders
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Somavaratan
rhGH
Sponsored by
About this trial
This is an interventional treatment trial for Growth Disorders focused on measuring 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
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Somavaratan
rhGH
Arm Description
Participants will receive somavaratan 3.5 milligrams (mg)/kilogram (kg) subcutaneous (SC) bolus injection twice monthly for 12 months.
Participants will receive commercially available rhGH (genotropin) 34 micrograms (μg)/kg once daily SC bolus injection for 12 months.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Change From Baseline in Body Weight at Month 12
Body weight measured in light clothing and without shoes.
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.
Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) at 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'.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02339090
Brief Title
Long-Acting Growth Hormone in Children Compared to Daily rhGH
Acronym
VELOCITY
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
August 26, 2015 (Actual)
Primary Completion Date
August 23, 2017 (Actual)
Study Completion Date
August 23, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Versartis Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The trial will compare a twice-monthly somavaratan dosing regimen for non-inferiority of treatment effect against daily injections of 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Growth Disorders
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
138 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Somavaratan
Arm Type
Experimental
Arm Description
Participants will receive somavaratan 3.5 milligrams (mg)/kilogram (kg) subcutaneous (SC) bolus injection twice monthly for 12 months.
Arm Title
rhGH
Arm Type
Active Comparator
Arm Description
Participants will receive commercially available rhGH (genotropin) 34 micrograms (μg)/kg once daily SC bolus injection for 12 months.
Intervention Type
Drug
Intervention Name(s)
Somavaratan
Other Intervention Name(s)
Long-acting recombinant human growth hormone, VRS-317
Intervention Description
Somavaratan will be administered per dose and schedule specified in the arm description.
Intervention Type
Drug
Intervention Name(s)
rhGH
Other Intervention Name(s)
daily growth hormone, recombinant growth hormone therapy
Intervention Description
rhGH will be administered per dose and schedule specified in the arm description.
Primary Outcome Measure Information:
Title
Annual Height Velocity
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change From Baseline in Height Standard Deviation Score (SDS) at Month 12
Description
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.
Time Frame
Baseline, Month 12
Title
Change From Baseline in Bone Age Relative to Chronological Age at Month 12, as Assessed by Central Reader
Description
Bone age was assessed from a radiograph of the left hand and wrist by central reader.
Time Frame
Baseline, Month 12
Title
Change From Baseline in Body Mass Index (BMI) at Month 12
Description
The BMI is a person's weight in kilograms (kg) divided by the square of height in meters.
Time Frame
Baseline, Month 12
Title
Change From Baseline in Body Weight at Month 12
Description
Body weight measured in light clothing and without shoes.
Time Frame
Baseline, Month 12
Title
Change From Baseline in Insulin-like Growth Factor 1 (IGF-I) SDS at Month 12
Description
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.
Time Frame
Baseline, Month 12
Title
Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) at Month 12
Time Frame
Baseline, Month 12
Title
Number of Participants With Adverse Events (AEs)
Description
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'.
Time Frame
Baseline up to Month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Will Charlton, MD
Organizational Affiliation
Sponsor GmbH
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Long-Acting Growth Hormone in Children Compared to Daily rhGH
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