Safety Study of Single Administration Post-exposure Prophylaxis Treatment for Marburg Virus

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety and pharmacology of single administrations of AVI-6003, a post-exposure prophylaxis candidate treatment for Marburg virus.

Detailed Description
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Marburg hemorrhagic fever is a rare human disease caused by the Marburg virus, a filamentous, single-stranded, negative-sense RNA virus. In general, the mortality rate associated with Marburg virus outbreaks has ranged from 23% to 88%, with the highest death rates seen in more recent epidemics. No vaccine or effective therapy is available for Marburg hemorrhagic fever. AVI-6003 is an experimental combination of 2 phosphorodiamidate morpholino antisense oligomers with positive charges on selected subunits (PMOplus™). These oligomers specifically target viral messenger RNA encoding 2 Marburg virus proteins thought to be important in viral replication and host immune suppression. The present study is designed to characterize the safety, tolerability and pharmacokinetics of escalating single-administration doses of AVI-6003 in healthy human subjects.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single-Dose, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of AVI-6003 in Healthy Adult Volunteers

Conditions
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Marburg Hemorrhagic Fever

Intervention / Treatment
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* Drug: AVI-6003
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female and between the ages of 18 and 50 years in good general health Volunteers must be willing to use barrier methods of contraception or be of non-childbearing potential Volunteers must be willing to undergo a urine screen for drugs of abuse Exclusion Criteria: Pregnancy or breastfeeding. Any clinically relevant abnormalities in physical examinations, vital signs, ECG, clinical chemistry, hematology or urinalysis Positive test for human immunodeficiency virus, hepatitis B or hepatitis C or known history of HIV infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVI-6003<br>Phosphorodiamidate morpholino antisense oligomer with positive charges on selected subunits (PMOplus™) | Drug: AVI-6003<br>* Single intravenous administration<br>|
| Placebo Comparator: Placebo<br>Normal saline | Drug: Placebo<br>* Single intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects experiencing adverse events |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma drug concentration |  | 28 days | 
| Urine drug concentration |  | 28 days |