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

• ClinicalTrials.gov Identifier: NCT00352911
• Recruitment Status: Completed
• First Posted: July 17, 2006
• Results First Posted: January 27, 2010
• Last Update Posted: March 9, 2010
• Sponsor: VGX Pharmaceuticals, LLC
• Information provided by: VGX Pharmaceuticals, LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: VGX-410 (Mifepristone); Drug: Placebo for VGX-410 (Mifepristone)	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: July 2006
• Actual Primary Completion Date: June 2007
• Actual Study Completion Date: November 2007

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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	Drug: VGX-410 (Mifepristone); Other Name: Mifeprex
Placebo Comparator: 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	Drug: Placebo for VGX-410 (Mifepristone)

Outcome Measures

Primary Outcome Measures :

1. Mean Log Change in Viral Load From Baseline (Day 1) to Day 56 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, District of Columbia

Georgetown University

Washington, District of Columbia, United States, 20007

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Veterans Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

VGX Pharmaceuticals, LLC

Investigators

• Principal Investigator: Princy Kumar, M.D.; Georgetown University
• Principal Investigator: Valerianna Amorosa, MD; Veteran's Hospital of Philadelphia
• Principal Investigator: Pablo Tebas, M.D.; University of Pennsylvania

More Information

• Responsible Party: VGX Pharmaceuticals, LLC
• ClinicalTrials.gov Identifier: NCT00352911
• Other Study ID Numbers: VT004
• First Posted: July 17, 2006
• Results First Posted: January 27, 2010
• Last Update Posted: March 9, 2010
• Last Verified: March 2010

Keywords provided by VGX Pharmaceuticals, LLC:

HIV-1

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mifepristone; Abortifacient Agents, Steroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptives, Oral, Synthetic; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Luteolytic Agents; Contraceptive Agents, Hormonal; Menstruation-Inducing Agents