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

Phase 2

Completed

Interventions: Drug: VGX-410 (Mifepristone)
Drug: Placebo for VGX-410 (Mifepristone)

Brief Summary: The objective of the study is to determine whether mifepristone (VGX-410) has anti-HIV-1 activity at doses of either 300 mg or 600 mg per day after oral administration for 14 days at each dose level.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
VGX-410 (Mifepristone)	VGX-410 (Mifepristone)	150mg twice daily of VGX-410 for 14 days and, if well tolerated, a dose escalation to 300mg twice daily of VGX-410 for 14 days
Placebo for VGX-410 (Mifepristone)	Placebo for VGX-410 (Mifepristone)	150mg twice daily of placebo for VGX-410 for 14 days and, if well tolerated, a dose escalation to 300mg twice daily of placebo for VGX-410 for 14 days

Primary Outcome Measures

Name	Time	Method
Mean Log Change in Viral Load From Baseline (Day 1) to Day 56	Baseline (Day 1) to Day 56	Mean log change in HIV RNA viral load (significant reduction is considered \>0.5 log 10) from baseline (Day 1) to Day 56 following 150mg twice daily for 14 days, dose escalation to 300mg twice daily for 14 days and then 28 days off treatment.

Secondary Outcome Measures

Name	Time	Method

Locations (3): Georgetown University
🇺🇸
Washington, District of Columbia, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Veterans Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States