A Randomized, Placebo-controlled, Dose Escalating, Phase II Trial of the Anti -HIV-Activity and Safety of VGX-410 (Mifepristone) in HIV-1 Infected Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 3
- 主要终点
- Mean Log Change in Viral Load From Baseline (Day 1) to Day 56
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: VGX-410 (Mifepristone) (Drug)
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
干预措施: Placebo for VGX-410 (Mifepristone) (Drug)
结局指标
主要结局
Mean Log Change in Viral Load From Baseline (Day 1) to Day 56
时间窗: 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.
次要结局
未报告次要终点