HIV Infections
Conditions
Keywords
HIV-1
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.
Interventions
DRUGPlacebo for VGX-410 (Mifepristone)
Sponsors
VGX Pharmaceuticals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VGX-410 (Mifepristone) 150mg twice daily for 14 days and if well tolerated, dose escalation to 300mg twice daily for 14 days | 16 |
| Placebo for VGX-410 (Mifepristone) 150mg twice daily for 14 days and if well tolerated, dose escalation to 300mg twice daily for 14 days | 3 |
| Total | 19 |
Baseline characteristics
| Characteristic | VGX-410 (Mifepristone) | Placebo for VGX-410 (Mifepristone) | Total |
|---|---|---|---|
| Age Continuous | 42.3 years STANDARD_DEVIATION 8 | 37.7 years STANDARD_DEVIATION 7.4 | 41.6 years STANDARD_DEVIATION 7.9 |
| Region of Enrollment United States | 16 participants | 3 participants | 19 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 14 Participants | 3 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 16 | 2 / 3 |
| serious Total, serious adverse events | 1 / 16 | 0 / 3 |
Outcome results
Primary
Mean Log Change in Viral Load From 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.
Time frame: Baseline (Day 1) to Day 56
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| VGX-410 (Mifepristone) | Mean Log Change in Viral Load From Baseline (Day 1) to Day 56 | 0.18 copies/mL on log scale | Standard Deviation 0.28 |
| Placebo for VGX-410 (Mifepristone) | Mean Log Change in Viral Load From Baseline (Day 1) to Day 56 | 0.42 copies/mL on log scale | Standard Deviation 0.39 |