Testing the AVI-7100 Flu Drug in Healthy Volunteers
Testing the AVI-7100 Flu Drug in Healthy Volunteers
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.
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.
-  INCLUSION CRITERIA:

 1. Age greater than or equal to 18 years and less than or equal to 60 years

 2. Body mass index (BMI) of 19-32 kg/m(2)

 3. Estimated glomerular filtration rate greater than or equal to 90 mL/min at
 screening, calculated using the MDRD formula

 4. Subjects must agree to:

 -  Not take any prescription or OTC medications with the exception of Tylenol, vitamins,
 seasonal allergy medications, and/or contraceptive medications for a period 7 days
 prior and during study drug administration.

 -  Not consume any alcohol for a period 2 days prior to and during study drug
 administration.

 5. One of the following in order to avoid pregnancy:

 -  Females who are able to become pregnant (i.e., are not postmenopausal)

 -  have not undergone surgical sterilization, and are sexually active with men) must
 agree to use at least 2 effective forms of contraception.

 -  From the date of the subject s signing of the informed consent form through 28 days
 after the last dose of study drug. At least one of the methods of contraception should
 be a barrier method.

 -  Males who have not undergone surgical sterilization and are sexually active with women
 must agree to use condoms plus have a partner use at least one additional effective
 form of contraception from the date of the subject s signing of the informed consent
 form through 28 days after the last dose of study drug.

 EXCLUSION CRITERIA:

 1. Any chronic medical problem that requires daily oral medications (except Tylenol, oral
 contraceptives, vitamins, and seasonal allergy medications), or other medical history
 that in the opinion of the investigator significantly increases the risk associated
 with a phase I drug.

 2. History of cardiovascular disease or unexplained syncope

 3. Women who are breast-feeding.

 4. Positive urine or serum pregnancy test.

 5. Abnormal ECG

 -defined as any clinically significant baseline Grade 1 or greater toxicity, or any
 Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity
 table.

 --evaluating PR interval, QTc interval and rhythm.

 6. Abnormal chemistry panel

 -defined as any clinically significant baseline Grade 1 or greater toxicity, or any
 Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity
 table

 --evaluating only sodium [Na], potassium [K], serum bicarbonate [total CO2],
 creatinine, glucose,albumin, ALT, AST, ALKP, GGT, total bilirubin, LDH, and estimated
 GFR by the MDRD equation.

 7. Abnormal complete blood count (CBC)

 -defined as any clinically significant baseline Grade 1 or greater toxicity, or any
 Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity
 table

 -- evaluating only the WBC (to include absolute neutrophil and lymphocyte counts),
 hemoglobin, hematocrit, and platelets.

 8. Abnormal urinalysis

 -defined as any clinically significant baseline Grade 1 or greater toxicity

 --evaluating only protein, and RBCs.

 9. Urine-albumin-to-creatinine ratio (UACR) >30 mg/g.

 10. Positive serology for Hepatitis B surface antigen.

 11. Positive serology for Hepatitis C.

 12. Positive serology for HIV-1.

 13. Positive urine drug screen.

 14. Participation in a study with receipt of any investigational drug within 5 half-lives
 or 30 days, whichever is longer, prior to study drug administration (i.e., Day 0)

 15. Donation of blood or blood products within 30 days or plasma within 2 weeks prior to
 study drug administration (i.e., Day 0)

 16. Receipt of blood products within 2 months prior to study drug administration (i.e.,
 Day 0)

 17. Receipt of any vaccination within 30 days prior to study drug administration (i.e.,
 Day 0)

 18. Any acute or chronic condition that, in the opinion of the Investigator, would limit
 the subject s ability to complete and/or participate in this clinical study.