Versartis International Trial in Adults With Long-Acting Growth Hormone

Study Overview
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Brief Summary
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A Phase 2, open-label dose-finding safety study of individualized monthly VRS-317 dosing for five months in adults with GHD.

Detailed Description
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A Phase 2, dose finding safety study to evaluate an individualized monthly VRS-317 dosing regimen in adults with GHD. This is an open-label, international, multicenter study with VRS-317 treatment for five months. This treatment period will include monthly dose titrations until a subject's mean IGF-I SDS value is within a target range for two consecutive months. Subjects will be stratified into three cohorts based on sensitivity to rhGH.

Official Title
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An Open-Label, Dose Finding, International Phase 2 Study With Once Monthly Subcutaneous VRS-317 in Adult Growth Hormone Deficiency (GHD)

Conditions
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Adult Growth Hormone Deficiency

Intervention / Treatment
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* Drug: somavaratan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects of childbearing potential must have negative pregnancy test and use appropriate contraceptive methods Subjects must have documented GHD during adulthood. Subjects taking other hormone replacement therapy must have been on a stable course of treatment for at least 3 months. Subjects with underlying disorders responsible for the subject's GHD must have been clinically stable for at least 6 months. Subjects receiving daily rhGH injections must washout for 14 days. Subjects must provide signed informed consent. Subjects must have a BMI (kg/m2) between 19.0 and 35.0. Exclusion Criteria: Subjects with diabetes mellitus or inadequate glucose control Subjects with untreated adrenal insufficiency. Subjects with free thyroxine outside the normal reference range. Subjects currently taking oral glucocorticoids, except for physiological maintenance doses of oral glucocorticoids in subjects with multiple pituitary hormone deficiencies. Subjects with current significant cardiovascular disease, heart insufficiency of NYHA class > 2. Subjects with current significant cerebrovascular, pulmonary, neurological, renal, inflammatory, or hepatobiliary disease. Subjects with current papilledema. Subjects with a history of persistent or recurring migraines. Subjects with current edema (≥ CTCAE Grade 2). Subjects with current drug or alcohol abuse. Subjects with a documented history of HIV, current HBV or HCV infection Subjects with a prior history of malignancy excluding adequately treated non-melanoma skin cancers or in situ carcinoma of the cervix. Women who are pregnant or breastfeeding. Subjects with a significant abnormality in Screening laboratory results

Ages Eligible for Study
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Minimum Age: 23 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Somavaratan in Older Adults<br>Long-acting recombinant human growth hormone therapy administered subcutaneously once monthly in subjects >= 35 years of age | Drug: somavaratan<br>* Long-acting recombinant human growth hormone therapy administered subcutaneously once monthly<br>* Other names: VRS-317;|
| Experimental: Cohort B: Somavaratan in Younger Adults<br>Long-acting recombinant human growth hormone therapy administered subcutaneously once monthly in subjects < 35 years of age | Drug: somavaratan<br>* Long-acting recombinant human growth hormone therapy administered subcutaneously once monthly<br>* Other names: VRS-317;|
| Experimental: Cohort C: Somavaratan in Women on Estrogen<br>Long-acting recombinant human growth hormone therapy administered subcutaneously once monthly in female subjects on oral estrogen (regardless of age) | Drug: somavaratan<br>* Long-acting recombinant human growth hormone therapy administered subcutaneously once monthly<br>* Other names: VRS-317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as measured by the number of subjects with adverse events, concomitant medications, safety labs, vital signs and physical exams | Safety observations include adverse events, concomitant medications, safety labs, vital signs and physical exams. | 5 months | 
| Starting doses (proportion of subjects who achieve normalization of IGF-I SDS response during the first dosing interval ) | To evaluate the starting doses of VRS-317 for each cohort as measured by the proportion of subjects who achieve normalization of IGF-I SDS response during the first dosing interval (one month after the first dose) | 5 months | 
| Dose titration plan (proportion of subjects who achieve a mean IGF-I SDS within the defined target range after each dose titration) | To evaluate the dose titration plan of VRS-317 for each cohort as measured by the proportion of subjects who achieve a mean IGF-I SDS within the defined target range after each dose titration | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of VRS-317 by measurement of serum anti-drug antibody (ADA) titers | To evaluate the immunogenicity of VRS-317 by measurement of serum anti-drug antibody (ADA) titers | 5 months | 
| Immunogenicity of VRS-317 by detection of neutralizing antibodies (NAbs) | To evaluate the immunogenicity of VRS-317 by detection of neutralizing antibodies (NAb) | 5 months | 

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