Open-label Extension Study to Evaluate the Safety of Long-term Twice-monthly Administration of Somavaratan in Adult Growth Hormone Deficiency (AGHD)

Study Overview
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Brief Summary
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Open-label extension study to evaluate the safety of long-term twice-monthly administration of somavaratan in adults with Growth Hormone Deficiency (GHD).

Detailed Description
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An open-label extension study to evaluate the safety of long-term twice-monthly administration of somavaratan in adults with GHD. This multicenter study is open to participants completing a Versartis adult GHD study as well as approximately 40 new somavaratan naïve participants (either recombinant human growth hormone [rhGH] treatment naïve or currently receiving daily rhGH therapy). All participants will receive twice-monthly (every 15 days ± 2 days) subcutaneous (SC) somavaratan. Doses will be titrated to each participant's individual insulin-like growth factor-I (IGF-I) responses based on the IGF-I level 7 days post-dose until a maintenance dose is achieved. Participants receiving somavaratan in a previous somavaratan study will have their dose decreased by half (minimum dose of 20 milligrams [mg], 40 mg for women on estrogen, rounded down to the nearest even number) and will be titrated per the Dose Titration Plan. New participants enrolling in this study will be assigned to one of two cohorts based on sensitivity to rhGH and titrated per the Dose Titration Plan.

Official Title
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An Open-Label, Long-Term Extension Study of the Safety of Somavaratan (VRS-317) in Adults With Growth Hormone Deficiency (GHD)

Conditions
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Adult Growth Hormone Deficiency (AGHD)

Intervention / Treatment
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* Drug: somavaratan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants of childbearing potential must have negative pregnancy test and use appropriate contraceptive methods Documented GHD during adulthood Participants naive to somavaratan must have an IGF-1 SDS value ≤ 0 at Screening Participants taking other hormone replacement therapy must have been on a stable course of treatment for at least 3 months Underlying disorders responsible for the participant's GHD must have been clinically stable for at least 6 months Participants receiving daily rhGH injections must washout for ≥ 14 days Body mass index (BMI) (kilograms [kg]/meter square [m^2]) between 18.0 and 40.0 Exclusion Criteria: Untreated adrenal insufficiency Recently diagnosed thyroid dysfunction which is not being treated or has not been stable on therapy for at least 3 months Currently taking anti-inflammatory dose of glucocorticoids that could potentially compromise safety or efficacy assessments Currently taking a GHRH or IGF-I product Current significant cardiovascular disease, heart insufficiency of New York Heart Association (NYHA) class > 2 Current significant disease thought to increase risk of receiving growth hormone or confound assessment of study outcomes History of diabetes mellitus or inadequate glucose control Current drug or alcohol abuse Current human immunodeficiency virus (HIV) wasting syndrome (HIV testing not required) History of malignancy in adulthood (participants with a history of childhood malignancy that were subsequently treated with rhGH in childhood and remain GHD in adulthood may be enrolled) Women who are pregnant or breastfeeding Treatment with an investigational drug other than somavaratan within 30 days prior to Screening A significant abnormality in Screening laboratory results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Somavaratan<br>Long-acting recombinant human growth hormone therapy administered subcutaneously twice-monthly in adult participants with GHD | Drug: somavaratan<br>* Long-acting recombinant human growth hormone therapy administered subcutaneously twice-monthly<br>* Other names: VRS-317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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'. | From first dose of study drug up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Dose Level During Titration/Maintenance | Total average dose received by a participant during titration/maintenance has been reported. | Up to Month 12 | 
| Number of Participants With Dose Adjustments | The number of participants with a dose adjustment (titrated up/down) at each month are summarized. | Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 | 
| Number of Participants Who Were Anti-drug Antibody (ADA) Positive |  | Up to approximately 2 years | 
| Number of Participants With Positive Neutralizing Antibodies (NABs) |  | Up to approximately 2 years | 
| Change From Baseline in Mean Insulin-like Growth Factor 1 (IGF-I) Standard Deviation Score (SDS) at Specified Timepoints During Maintenance Period | Changes in the IGF-I levels were assessed as Standard Deviation Scores (SDS). The SDS 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 standard deviation (SD) vary depending on the age and sex of the participant. Change in IGF-I level (SDS) at specified timepoints from baseline was assessed. A higher score reflects a better outcome. | Baseline, Month 2 Day 1, Month 2 Day 8, Month 3 Day 1, Month 3 Day 8, Month 4 Day 1, Month 4 Day 8, Month 5 Day 1, Month 5 Day 8, Month 6 Day 1, Month 6 Day 8, Month 7 Day 1, Month 7 Day 8, Month 8 Day 1, Month 8 Day 8, Month 10 Day 1, and Month 10 Day 8 | 
| Mean Insulin-like Growth Factor-binding Protein 3 (IGFBP-3) SDS During Maintenance Period |  | Baseline up to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Versartis, somavaratan, Growth Hormone Deficiency, Adult Growth Hormone Deficiency, AGHD, Growth Hormone Replacement, XTEN, VRS-317, Long Acting Growth Hormone, Growth Hormone Replacement Therapy