A Phase 1, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of AVI-7100 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Influenza
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 66
- Locations
- 1
- Primary Endpoint
- To evaluate the safety and tolerability of AVI-7100 in healthy adults, following single- or multiple-dose, intravenous administration at escalating dose-levels
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
Background:
- Influenza (flu) is a virus that causes people to get sick. Most of the time, the flu causes only a mild illness, but some people can become seriously ill or even die from it. Currently, some pills and inhaled powders can be used to treat the flu, but they only make flu symptoms end about a day sooner. More treatment choices for the flu are needed, especially for those who become seriously ill. Researchers want to test a new drug, AVI-7100, that might keep a person who takes it from having a more serious case of the flu.
Objectives:
- To see how healthy adult volunteers tolerate the AVI-7100 anti-influenza drug.
Eligibility:
- Healthy volunteers of normal weight between 18 and 60 years of age.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. A heart function test will also be performed.
- Participants will have either AVI-7100 or a placebo infusion. They will not know which infusion they have. . Participants will stay at the clinical center for a total of 8 hours after the infusion. Blood samples will be collected 1, 2, 4, and 8 hours after the end of the infusion
- Participants will return on Days 1, 2, 4, 10, and 28 after receiving the drug. Blood and urine samples will be collected. A heart function test will also be performed.
- There will be a second part of the study that is separate from the first one. Additional people will receive either AVI-7100 or placebo to test their reactions to a specific dose.
Detailed Description
Despite currently available antivirals, influenza causes significant morbidity and mortality (estimated 36,000 deaths each year in the United States alone). More agents are needed in the armamentarium of anti-influenza medications including novel mechanisms of action and parenteral agents. This study will evaluate the safety of a novel RNA based therapeutic AVI-7100. Beginning with a low single-dose, subjects are randomized to receive either AVI-7100 or placebo and evaluated on Study Days 0, 1, 2, 4, 10, 28. The safety and tolerability is evaluated using symptoms, clinical laboratory tests, ECG, and pharmacokinetics. Utilizing a series of stopping rules and a medical monitor, the dose will be escalated as safety and tolerability are established. Once the maximum tolerated dose (MTD) is established in the first part of this study (either limited by adverse effects or up to maximum anticipated dose), the safety and tolerability of multi-dose administration will begin (replicating anticipated clinical use). Subjects again are randomized to either AVI-7100 or placebo daily for 5 days, and evaluated on Study Days 0, 1, 2, 3, 4, 5, 6, 8, 14, and 32. The dose used in the multi-dose cohorts will also be escalated as safety and tolerability are established.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
To evaluate the safety and tolerability of AVI-7100 in healthy adults, following single- or multiple-dose, intravenous administration at escalating dose-levels
Time Frame: 2 years
Secondary Outcomes
- To evaluate the pharmacokinetics of intravenously administered AVI-7100 in healthy adults, following single- or multiple-dose, intravenous administration at escalating dose-levels(2 years)