Open-label Extension Study to Evaluate the Safety of Long-term Twice-monthly Administration of Somavaratan in Adult Growth Hormone Deficiency (AGHD)
Primary Purpose
Adult Growth Hormone Deficiency (AGHD)
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
somavaratan
Sponsored by
About this trial
This is an interventional treatment trial for Adult Growth Hormone Deficiency (AGHD) focused on measuring VRS-317, Long Acting Growth Hormone, Versartis, somavaratan, Growth Hormone Deficiency, Adult Growth Hormone Deficiency, AGHD, Growth Hormone Replacement, Growth Hormone Replacement Therapy, XTEN
Eligibility Criteria
Inclusion Criteria:
- Female subjects of childbearing potential must have negative pregnancy test and use appropriate contraceptive methods
- Documented GHD during adulthood
- Subjects naive to somavaratan must have an IGF-1 SDS value ≤ 0 at Screening
- Subjects taking other hormone replacement therapy must have been on a stable course of treatment for at least 3 months
- 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
- BMI (kg/m2) 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 HIV wasting syndrome (HIV testing not required)
- History of malignancy in adulthood (subjects 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Somavaratan
Arm Description
Long-acting recombinant human growth hormone therapy administered subcutaneously twice-monthly in adult participants with GHD
Outcomes
Primary Outcome Measures
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'.
Secondary Outcome Measures
Average Dose Level During Titration/Maintenance
Total average dose received by a participant during titration/maintenance has been reported.
Number of Participants With Dose Adjustments
The number of participants with a dose adjustment (titrated up/down) at each month are summarized.
Number of Participants Who Were Anti-drug Antibody (ADA) Positive
Number of Participants With Positive Neutralizing Antibodies (NABs)
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.
Mean Insulin-like Growth Factor-binding Protein 3 (IGFBP-3) SDS During Maintenance Period
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02719990
Brief Title
Open-label Extension Study to Evaluate the Safety of Long-term Twice-monthly Administration of Somavaratan in Adult Growth Hormone Deficiency (AGHD)
Official Title
An Open-Label, Long-Term Extension Study of the Safety of Somavaratan (VRS-317) in Adults With Growth Hormone Deficiency (GHD)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Phase 3 clinical trial of somavaratan in pediatric growth hormone deficiency (PGHD) did not meet its primary endpoint of non-inferiority.
Study Start Date
February 11, 2016 (Actual)
Primary Completion Date
January 11, 2018 (Actual)
Study Completion Date
January 11, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Versartis Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Growth Hormone Deficiency (AGHD)
Keywords
VRS-317, Long Acting Growth Hormone, Versartis, somavaratan, Growth Hormone Deficiency, Adult Growth Hormone Deficiency, AGHD, Growth Hormone Replacement, Growth Hormone Replacement Therapy, XTEN
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Somavaratan
Arm Type
Experimental
Arm Description
Long-acting recombinant human growth hormone therapy administered subcutaneously twice-monthly in adult participants with GHD
Intervention Type
Drug
Intervention Name(s)
somavaratan
Other Intervention Name(s)
VRS-317
Intervention Description
Long-acting recombinant human growth hormone therapy administered subcutaneously twice-monthly
Primary Outcome Measure Information:
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
From first dose of study drug up to approximately 2 years
Secondary Outcome Measure Information:
Title
Average Dose Level During Titration/Maintenance
Description
Total average dose received by a participant during titration/maintenance has been reported.
Time Frame
Up to Month 12
Title
Number of Participants With Dose Adjustments
Description
The number of participants with a dose adjustment (titrated up/down) at each month are summarized.
Time Frame
Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
Title
Number of Participants Who Were Anti-drug Antibody (ADA) Positive
Time Frame
Up to approximately 2 years
Title
Number of Participants With Positive Neutralizing Antibodies (NABs)
Time Frame
Up to approximately 2 years
Title
Change From Baseline in Mean Insulin-like Growth Factor 1 (IGF-I) Standard Deviation Score (SDS) at Specified Timepoints During Maintenance Period
Description
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.
Time Frame
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
Title
Mean Insulin-like Growth Factor-binding Protein 3 (IGFBP-3) SDS During Maintenance Period
Time Frame
Baseline up to Month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
Learn more about this trial
Open-label Extension Study to Evaluate the Safety of Long-term Twice-monthly Administration of Somavaratan in Adult Growth Hormone Deficiency (AGHD)
We'll reach out to this number within 24 hrs