Pharmacokinetic Study of a Single Dose of AVI-4065 in Cerebral Spinal Fluid

Pharmacokinetic Study of AVI-4065 in Cerebral Spinal Fluid Among Healthy Adult Males Following Subcutaneous Administration

AVI-4020 Injection, a phosphorodiamidate Morpholino oligomer (PMO), was found to cross the blood-brain barrier during a study of patients with presumptive West Nile virus disease. AVI-4065, which was designed to target HCV, is also a PMO; its ability to cross the blood-brain barrier is unknown. In this study, a single dose of AVI-4065 will be subcutaneously injected, and samples collected to determine if this drug crosses the blood-brain barrier. If it does, then additional investigations could be performed in people with severe forms of HCV disease in which the brain is affected.

AVI-4020 Injection, a phosphorodiamidate Morpholino oligomer (PMO), was found to cross the blood-brain barrier during a study of patients with presumptive West Nile virus disease. AVI-4065, which was designed to target HCV, is also a PMO; its ability to cross the blood-brain barrier is unknown. As the incidence of HCV disease has grown, the knowledge base of this disease has likewise increased.

Encephalopathy is a recognized consequence in some patients with HCV infection. In this study, a single dose of AVI-4065 will be subcutaneously injected, and samples collected to determine if this drug crosses the blood-brain barrier. If it does, then additional investigations could be performed in people with HCV disease in which the brain is affected.

Inclusion Criteria:

• Adult males 18 years to 64 years of age;
• Good general health (as evidenced by no chronic conditions, normal physical exam, vital signs within normal limits; laboratory evaluations within normal range)
• Signed and dated written informed consent form; and
• Willing to participate in all study activities and all requirements, including effective contraception (viz., a double-barrier method) during the 7-day study surveillance period.

Exclusion Criteria:

• Hematology, serum chemistry (exclusive of electrolytes), and urinalysis laboratory test values >2 times upper limits of normal or anemia (hemoglobulin <11 g/dL), leukopenia (total white blood count <3,000/µL or total neutrophils <1,500/ µL) or thrombocytopenia (platelets <100,000/µL). Electrolytes and coagulation values exceeding normal ranges are to be excluded.
• Body Mass Index (BMI) >35.
• Calculated creatinine clearance (by the Cockroft and Gault Formula) <70 mL/min, based on age and gender.
• Positive HIV-1 or HIV-2 serology.
• Positive HCV serology and/or positive plasma HCV-RNA status.
• Positive HBsAg or HBcAb status.
• Solid or hematopoetic organ transplant recipient.
• Active illness or recent illness within 30 days of the first dose of study drug.
• History of any of the following: brain injury, neoplasm, chronic or migraine headaches, cancer, meningitis or hydrocephalus.
• Usage of any prescribed, over-the-counter or illicit drug(s) within 30 days of study drug administration. Use of herbal remedies and/or supplements at the discretion of the Investigator.
• Unwilling to practice effective contraception during the study period.
• Participation in any clinical interventional trial within the previous 6 months.
• Positive drug urine screen.