Clinical trial NCT03401528: A Phase 1 AVB-S6-500 Safety and Tolerability Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Aravive, Inc.
Sponsor class: INDUSTRY
First posted: 2018-01-17
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This study has two portions: a single ascending dose (SAD) portion consisting of 4 sequential dose escalation cohorts, and a repeat dose (RD) portion. In both study portions, subjects are randomized to receive either a study intervention (AVB-S6-500) or a placebo.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability of AVB-S6-500 - Adverse events
timeFrame: Up to 6 weeks
measure: Safety and tolerability of AVB-S6-500 - ECG
timeFrame: Up to 6 weeks
measure: Safety and tolerability of AVB-S6-500 -physical examination
timeFrame: Up to 6 weeks
measure: Safety and tolerability of AVB-S6-500 - vital sign
timeFrame: Up to 6 weeks
measure: Safety and tolerability of AVB-S6-500 - clinical laboratory assessments
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: AUC
timeFrame: Up to 6 weeks
measure: Cmax
timeFrame: Up to 6 weeks
measure: Ctrough
timeFrame: Up to 6 weeks
measure: Tmax
timeFrame: Up to 6 weeks
measure: λz
timeFrame: Up to 6 weeks
measure: t1/2
timeFrame: Up to 6 weeks
measure: CL
timeFrame: Up to 6 weeks
measure: V
timeFrame: Up to 6 weeks
measure: Pharmacodynamic parameter
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: Orlando Clinical Research Center
name: Thomas C Marbury, MD
role: PRINCIPAL_INVESTIGATOR
References: