Antiviral Activity and Safety of Mifepristone at 2 Doses in HIV-1 Infected Subjects

VT004 is a double-blind, randomized, placebo-controlled Phase II study of two doses of orally administered mifepristone (VGX-410) (300 and 600 mg) taken as a twice daily (BID) dosage (150mg BID and 300mg BID) in a dose-escalating fashion for 14 days at each dose level to determine antiviral activity and safety in HIV-1-infected participants. At entry, 18 subjects will be randomized in a 5:1 fashion (15 on active drug: 3 on placebo) to receive escalating doses of VGX-410 or matching placebo. Patients will be randomized to receive 300 mg (as 150 mg BID dose) of VGX-410 or matching placebo for 14 days. In patients that complete this dose without significant safety concerns or side effects, the dose will be increased to 600 mg (as 300 mg BID dose) or matching placebo for 14 days. Patients must meet all inclusion/exclusion criteria listed below and be seen on a weekly basis by study personnel while on study drug. Patients must return ~ one month after finishing the study therapy for examination and safety labs.

Inclusion criteria

• HIV-1 infection
• CD4 cell count > 200
• Plasma HIV-1 RNA > 2000 copies/mL and have not received antiretroviral therapy within the 16 weeks prior to entry
• Absolute neutrophil count > 750/mm3
• Hemoglobin > 10 g/dL
• Platelet count > 100,000 mm3
• Creatinine < 2 X upper limit of normal [ULN] (fasting)
• AST (SGOT), ALT (SGPT), and alkaline phosphatase < 2 X ULN
• Total bilirubin < 2.5 X ULN
• Albumin > 3 g/dL
• Serum lipase < 1.5 X ULN
• Thyroid stimulating hormone (TSH) within normal limits
• Plasma cortisol > 20 mcg/dL, 30 minutes after cosyntropin administration
• Negative pregnancy test and willing to use effective birth control during the study
• Karnofsky performance score > 80 within 30 days prior to study entry
• Men and women >= 18 years of age

Exclusion criteria

• Receipt of antiretroviral treatment within the 16 weeks prior to study entry
• Chronic adrenal failure, adrenal insufficiency, personal or family history of autoimmune endocrine disease, history of active hepatitis B or C, or current treatment for hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Presence of diabetes mellitus
• Pregnancy within 90 days prior to study entry or breast-feeding
• Dysfunctional uterine bleeding within the 12 months prior to study entry
• Any current hormonal contraception or intrauterine device (IUD) use
• Use of drugs that are inhibitors or inducers of metabolism by the cytochrome P450 3A4 within 7 days prior to study entry
• Use of systemic corticosteroids or hormonal agents within 90 days prior to study entry
• Use of any immunomodulator, HIV vaccines, or investigational therapy within 90 days prior to study entry
• Any vaccination within 30 days prior to study entry
• Use of systemic cytotoxic chemotherapy within 90 days prior to study entry
• History of allergy to mifepristone or its formulations
• Active drug or alcohol use
• Serious illness requiring systemic treatment and/or hospitalization for at least 14 days prior to study entry
• Weight < 40 kg or 88 lbs. within 90 days prior to study entry