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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: AVB-S6-500
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional 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.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose - AVB-S6-500<br>Four sequential dose escalation cohorts - patients are randomized either to investigational drug or matching placebo | Drug: AVB-S6-500<br>* AVB-S6-500 is an investigational drug.<br>* Other names: AVB500;|
| Placebo Comparator: Single Ascending Dose - placebo<br>Four sequential dose escalation cohorts - patients are randomized either to investigational drug or matching placebo | Other: Placebo<br>* Matching placebo<br>|
| Experimental: Repeat Dose - AVB-S6-500<br>Four single doses of the investigational drug or matching placebo - patients are randomized either to investigational drug or matching placebo | Drug: AVB-S6-500<br>* AVB-S6-500 is an investigational drug.<br>* Other names: AVB500;|
| Placebo Comparator: Repeat Dose - placebo<br>Four single doses of the investigational drug or matching placebo - patients are randomized either to investigational drug or matching placebo | Other: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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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 |