Long-Acting Growth Hormone in Children Compared to Daily rhGH

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02339090

Acronym

VELOCITY

Enrollment

138

Registered

2015-01-15

Start date

2015-08-26

Completion date

2017-08-23

Last updated

2022-12-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

DRUGSomavaratan

Somavaratan will be administered per dose and schedule specified in the arm description.

DRUGrhGH

rhGH will be administered per dose and schedule specified in the arm description.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

3 Years to 11 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Annual Height Velocity	12 months	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

Measure	Time frame	Description
Change From Baseline in Bone Age Relative to Chronological Age at Month 12, as Assessed by Central Reader	Baseline, Month 12	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	Baseline, 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	Baseline, Month 12	Body weight measured in light clothing and without shoes.
Change From Baseline in Height Standard Deviation Score (SDS) at Month 12	Baseline, 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 Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) at Month 12	Baseline, Month 12	—
Number of Participants With Adverse Events (AEs)	Baseline up to Month 12	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'.
Change From Baseline in Insulin-like Growth Factor 1 (IGF-I) SDS at Month 12	Baseline, 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.

Participant flow

Pre-assignment details

Participants were stratified by region (North America and Europe), age (above and below anticipated median age of 7.5 years) and baseline Insulin-like growth factor-I (IGF-I) standard deviation score (SDS) (above and below anticipated median of -1.7) and randomized in a 3:1 ratio to receive either somavaratan or recombinant human growth hormone (rhGH).

Participants by arm

Arm	Count
Somavaratan Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months.	104
rhGH Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months.	32
Total	136

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Lost to Follow-up	0	1
Overall Study	Non-compliance With Study Drug	0	1
Overall Study	Poor Growth	3	0
Overall Study	Randomized but not treated	0	2
Overall Study	Withdrawal by Subject	2	1

Baseline characteristics

Characteristic	rhGH	Total	Somavaratan
Age, Continuous	6.9 years STANDARD_DEVIATION 2.38	7.0 years STANDARD_DEVIATION 2.11	7.0 years STANDARD_DEVIATION 2.03
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	11 Participants	8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants	125 Participants	96 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	5 Participants	5 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	7 Participants	6 Participants
Race (NIH/OMB) White	31 Participants	122 Participants	91 Participants
Sex: Female, Male Female	10 Participants	56 Participants	46 Participants
Sex: Female, Male Male	22 Participants	80 Participants	58 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 104	0 / 32
other Total, other adverse events	59 / 104	16 / 32
serious Total, serious adverse events	6 / 104	0 / 32

Outcome results

Primary

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.

Time frame: 12 months

Population: ITT population included all randomized participants.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Somavaratan	Annual Height Velocity	9.43 cm/year	Standard Error 0.28
rhGH	Annual Height Velocity	10.70 cm/year	Standard Error 0.48

Comparison: An ANCOVA model will be used to determine the adjusted (least squares) means and standard error (SE) to determine the confidence interval (CI) of the difference. ANCOVA model included treatment group, region, and gender as fixed effects; with baseline age and baseline IGF-I SDS as covariates.95% CI: [-2.32, -0.24]

Secondary