A Phase 1 AVB-S6-500 Safety and Tolerability Study

A Single-blind, Randomized, Placebo-controlled, Phase 1, Single Ascending-dose and Repeat-dose, Safety and Tolerability Study of Intravenous AVB-S6-500 in Healthy Subjects

This is a randomized single-blind, placebo-controlled, Phase 1, single ascending dose (SAD) and repeat dose (RD), safety and tolerability study of AVB-S6-500 in healthy subjects. A SAD portion of the study consists of 4 sequential dose escalation cohorts, whereas RD portion of the study consists of a single cohort receiving 4 weekly doses of AVB-S6-500. In both SAD and RD study arms, subjects are randomized to receive either a study intervention (AVB-S6-500) or matching placebo.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Other: Placebo; Drug: AVB-S6-500

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or female
• Age 18 - 55
• Body mass index (BMI) ranging between 18 and 30 kg/m2, inclusive
• Negative urine drug screen/alcohol breathalyzer results at Screening and at Day -1
• Has not used tobacco products during the 3 months prior to Screening and agrees to refrain from use throughout the study duration
• Female subjects of child-bearing potential must agree to use one of the study-approved effective contraceptive methods for the duration of the study and through 1 month after completion of the final study visit
• Male subjects must be either surgically sterilized or agree to use study-approved effective contraceptive methods for the duration of the study and through 1 month after completion of the final study visit
• If female, a negative serum pregnancy test at Screening and urinary pregnancy test at Day -1 is required
• Able to read, understand, and provide signed informed consent
• Able to communicate adequately with the investigator and to comply with the requirements for the entire study.

Exclusion Criteria:

• Blood pressure ≥ 140/90 mmHg or pulse > 100 beats/minute at Screening
• QTc intervals corrected for heart rate via the Fridericia method (QTcF) > 450 msec (males) and > 480 msec (females) at Screening
• Pregnant or a nursing female
• Male with a pregnant partner
• Currently enrolled in another clinical trial or has received treatment with an investigational drug during the 30 days (or 5 half-lives, whichever is longer) prior to dosing
• History of substance or alcohol abuse or dependency within the past
• Used any medications or over the-counter products within 14 days or 5 half lives (whichever is longer) prior to administration of study medication, including analgesics, hormonal contraceptives (oral contraceptive pills or implant), natural food supplements, or dietary or herbal supplements including vitamins)
• Donated blood in excess of 500 mL within 56 days prior to the dosing or intention of donating during the study through the month after completing the study
• Positive test results for hepatitis B virus (HBV) surface antigen, hepatitis C virus antibody (HCV), or human immunodeficiency virus (HIV)
• History or presence of any condition that, in the opinion of the Investigator, could interfere with the study conduct or observation
• A medical history of or any current clinically significant disorder, including but not limited to: asthma, angioedema, bronchospasm, ulcer disease, gastrointestinal bleeding, coagulation defects, hypertension, edema, heart failure, hypokalemia, cardiovascular disease, hypersensitivity reaction to any biologic drug, significant dermatologic diseases or condition that would significantly influence the immune response
• A serious illness, medical surgical procedure, or trauma resulting in missed work or hospitalization within the 30 days preceding the beginning of study treatment
• Received treatment for any type of cancer within the 5 years prior to enrollment
• An employee, family member, or student of the Investigator or clinical site

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single Ascending Dose - AVB-S6-500; Four sequential dose escalation cohorts - patients are randomized either to investigational drug or matching placebo	Drug: AVB-S6-500; AVB-S6-500 is an investigational drug.; Other Names: AVB500
PLACEBO_COMPARATOR: Single Ascending Dose - placebo; Four sequential dose escalation cohorts - patients are randomized either to investigational drug or matching placebo	Other: Placebo; Matching placebo
EXPERIMENTAL: Repeat Dose - AVB-S6-500; Four single doses of the investigational drug or matching placebo - patients are randomized either to investigational drug or matching placebo	Drug: AVB-S6-500; AVB-S6-500 is an investigational drug.; Other Names: AVB500
PLACEBO_COMPARATOR: Repeat Dose - placebo; Four single doses of the investigational drug or matching placebo - patients are randomized either to investigational drug or matching placebo	Other: Placebo; Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of AVB-S6-500 - Adverse events	Monitoring of adverse events	Up to 6 weeks
Safety and tolerability of AVB-S6-500 - ECG	Monitoring of 12 lead ECGs	Up to 6 weeks
Safety and tolerability of AVB-S6-500 -physical examination	Physical examination of body systems	Up to 6 weeks
Safety and tolerability of AVB-S6-500 - vital sign	Vital sign measurment	Up to 6 weeks
Safety and tolerability of AVB-S6-500 - clinical laboratory assessments	Routine lab hematology, serum chemistry and coagulation	Up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC	Area under the curve	Up to 6 weeks
Cmax	Maximum observed concentration	Up to 6 weeks
Ctrough	Serum concentration observed at end of a single dose and observed pre-dose during repeat doses	Up to 6 weeks
Tmax	Time to reach maximum observed plasma concentration	Up to 6 weeks
λz	Terminal phase elimination rate constant	Up to 6 weeks
t1/2	Terminal half-life	Up to 6 weeks
CL	The total body clearance	Up to 6 weeks
V	Volume of distribution	Up to 6 weeks
Pharmacodynamic parameter	Concentration of the drug target	Up to 6 weeks

Collaborators and Investigators

• Sponsor: Aravive, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 31, 2018
• Primary Completion (ACTUAL): June 20, 2018
• Study Completion (ACTUAL): July 31, 2018

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 16, 2018
• First Posted (ACTUAL): January 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: AVB500-HV-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No