VRS-317 in Adult Subjects With Growth Hormone Deficiency

Growth Hormone Deficiency Clinical Trial

Official title: A Blinded Placebo Controlled Single Ascending Dose Phase 1 for Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Subcutaneous Administration of VRS-317 in Adults With Growth Hormone Deficiency

Status Completed

Clinical Trial Summary

The purpose of this research study is to determine the safety and tolerability of up to five doses of VRS-317 in Adult Growth Hormone Deficient patients.

• Patients will be evaluated for evidence of activity of VRS-317 by measurement of changes from baseline in insulin-like growth factor-1 (IGF-I) and binding protein (IGFBP-3), and bone turnover (bone alkaline phosphatase)

• Descriptive pharmacokinetic (PK) and pharmacodynamic (PD) parameters (IGF-I and IGFBP-3) will be determined by standard model independent methods based on the plasma concentration-time data of each subject. These parameters include: Cmax, Tmax, AUCavg, AUC0-inf, and t1/2.

• The purpose is to determine the appropriate dose of VRS-317 to maintain a normal range (for appropriate age/gender) for IGF-I levels in adult patients for up to one month after administration of a single dose

Clinical Trial Description

The study is a placebo controlled single ascending dose (SAD) study in adult GHD patients currently receiving daily rhGH therapy. After screening patients are withdrawn from daily rhGH therapy for a minimum of 7 days (maximum of 60 days) prior to randomization for treatment. Patients will be randomised within a treatment group that is currently being enrolled once the patient has passed the pre-dose screening criteria.

Documented confirmation (medical history) of GHD during adulthood by a minimum of one or more GH stimulation tests is required such as:

• insulin tolerance test (ITT; peak hGH ≤ 5.0 ng/mL),

• arginine alone (peak hGH ≤ 0.4 ng/mL);

• arginine + growth-hormone-releasing hormone* (see below);

• or glucagon stimulation test (peak hGH ≤ 3.0 ng/mL) OR

• at least 3 other pituitary hormone deficiencies and a low IGF-I for age/gender appropriate normal range

Each patient will be randomised to receive either the investigational product, VRS-317 (Cohorts A-E), or placebo (Cohort F) in a 4:1 ratio.

Subjects will be monitored for safety throughout their participation in the study. To ensure patient safety, two patients (1 active, 1 placebo) in the first treatment group, one from Cohort A and one from Cohort F1, will be dosed in a blinded manner and monitored for 48 hr prior to dosing the remaining 8 patients. The 8 remaining patients will be blinded and randomized to the first treatment group. Vital signs, clinical lab values, adverse events (AEs) and concomitant medications (CMs) will be captured. AEs will be graded using the Common Terminology Criteria for Adverse Events (CTCAE v 4.0)1, and the Primary Dermal Irritation Scoring Scale; AEs will be coded using the MedDRA2 dictionary and CMs using the WHO Drug dictionary. Prior to escalating to a higher dose level, safety data will be reviewed by the principal investigator (PI), co-PIs, the Sponsor, and the medical monitor for any potential safety risk to subjects.

Patients will participate for a total of 83-215 days. A 7-60 day withdrawal phase (no daily rhGH therapy) is followed by receiving assigned doses on Day 1 of Treatment Phase, PK/PD and safety assessments for 30 days, and an additional 30 days of follow up.

Safety evaulations will be performed to assess safety including but not limited to:

• Physical examination

• Vital signs (including sitting/supine blood pressure)

• Laboratory tests: hematology, chemistry, urinalysis, and pregnancy testing (in women of child-bearing age)

• Adverse events and concomitant medications

• Glucose metabolism: Fasting and post-prandial plasma glucose and fasting insulin pre-study and at pre-scheduled timepoints during the study (per Assessment Table)

• Lipid profile will be assessed pre-study and at pre-scheduled timepoints during the study (per Assessment Table)

• Assessment for adrenal insufficiency prior to enrollment and at Day 30 (not performed on patients with documented history of adrenal insufficiency)

• Evaluation of injection site reactions

• Anti-VRS-317 antibody assay (pre-dose, Day 30 (end of study) and Day 60) last follow up visit

• Safety monitoring will continue for up to 60 days post-dose ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency

• NCT number: NCT01359488
• Study type: Interventional
• Source: Versartis Inc.
• Status: Completed
• Phase: Phase 1
• Start date: March 2011
• Completion date: July 2012