Phase 2 Safety and Efficacy Study of Bevirimat Functional Monotherapy in HIV Treatment-Experienced Patients for 2 Weeks*

HIV Infections Clinical Trial

Official title:

Phase 2 Dose-escalating, P-C, D-B, Parallel Group Study in HIV Treatment-experienced Patients to Evaluate the Safety, Tolerability and Efficacy of PA103001-04 Administered as Functional Monotherapy for 14 Days *(PART B)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00511368
• Other study ID #: PA103001-04 Study 203
• Status: Completed
• Phase: Phase 2
• First received: August 1, 2007
• Last updated: January 15, 2010
• Start date: April 2006
• Est. completion date: July 2008

Study information

• Verified date: January 2010
• Source: Myrexis Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate antiretroviral activity of up to five different oral doses administered for two weeks of bevirimat versus placebo in HIV treatment experienced patients, who have documented genotypic resistance to at least one major mutation from the IAS-USA list (2007)of resistance mutations for NRTIs, NNRTIs, or PIs. Patients will also be monitored for side effects, and the pharmacokinetics of bevirimat will be determined.

Description:

Bevirimat (PA103001-04) represents a new class of antivirals that blocks HIV replication by disrupting virus maturation; specifically, by inhibiting a late step in the Gag processing cascade. Short term (7-10 days) functional monotherapy studies (conducted in patients with detectable viral loads on a failing regimen)help in determining the potency of the drug, and enable dose finding. This is a two part (A and B)randomized, placebo-controlled, double-blind, multiple-dose, dose-escalation study in HIV treatment-experienced patients on a failing regimen (harboring resistance mutations to at least one member of the NRTI, NNRTI or PI classes. The antiretroviral activity, safety, and pharmacokinetics of up to 5 different dose levels of bevirimat will be compared to placebo when added to a failing approved antiretroviral regimen. The study is conducted in two parts: A and B. In Part A following 14 days of daily dosing patients commenced a new optimized ART regimen in addition to their randomized treatment. In Part Part B dosing with the randomized treatment ends after the initial 14 days of daily dosing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male or female. Females of child-bearing potential, must have a documented negative pregnancy test and be willing to utilize double-barrier contraception through-out the study period.

• Have HIV-1-infection.

• Have a screening plasma HIV-1 RNA value, measured by the Roche Amplicor assay, of 2,000 - 250,000 copies/ml (inclusive).

• Have documented evidence of genotypic resistance in their medical records (at screening) or have resistance at screening by genotype to any major mutation from the IAS-USA list of resistance drug mutations, defined as: NRTI resistance: M41L, K65R, D67N, K70R, K70E, L74V, Y115F, M184V, M184V/I, L210W, T215Y/F, K219Q/E; NNRTI resistance: L100I, K103N, V106M, V106A/M, V108I, Y181C, Y181C/I, Y188L, Y188C/L/H, G190S/A, G190A, P225H; Major PI resistance: D30N, V32I, L33F, M46I/L, I47V/A, G48V, I50L, I50V, I54M/L, L76V, V82A/F/T, V82A/F/T/S, V82L/T, I84V, N88S, L90M

• Be receiving an antiretroviral therapy regimen containing at least 3 drugs (regimens containing ritonavir must not exceed a total daily dose of 400 mg) which has been unchanged for at least 8 weeks prior to initial screening.

• Be able to receive an optimized background regimen.

• Be free from any acute infection or serious medical illness within 14 days prior to study entry.

• Be informed of the nature of the study and provide written informed consent.

• Be willing to comply with the meal requirements described in the protocol.

Exclusion Criteria:

• Current opportunistic infection characteristic of AIDS

• Patients unable or unwilling to comply with the dosing schedule and protocol evaluations.

• Patients with malabsorption syndromes affecting drug absorption.

• Patients with systolic blood pressure < 90 mmHg or > 140 mmHg or diastolic blood pressure < 60 mmHg or > 90 mmHg measured in a semi-recumbent position after at least 10 minutes of rest at the screening or qualification visit.

• A history of seizures (excluding pediatric febrile seizures), migraines, cluster and/or chronic headaches, cerebrovascular accident (CVA) or transient ischemic attacks (TIA).

• Patients with abnormal Hemoglobin (< 10.0 g/dL for men and < 9.0 g/dL for women), Neutrophil count (< 1000/mm3), Platelet count (< 100,000/mm3), AST or ALT > 2.5 times the upper limit of normal (patients with a positive HBV surface antigen or HCV antibody test at screening must have AST and ALT no more than 1.5 times the upper limit of normal)

• Patients who have received radiation therapy or cytotoxic chemotherapeutic agents, immunomodulating agents, HIV immunotherapeutic vaccine, an investigational drug or product, or participation in a drug study within 4 weeks prior to the first dose of study drug.

• A history of alcoholism or drug addiction within the past 1 year (unless enrolled in a treatment program and approved by the sponsor). Recent use of any recreational drugs (except marijuana).

• A history of difficulty donating blood or inadequate venous access.

• The donation of blood or plasma within 30 days prior to receiving study medication.

Note: patients with a CD4 count <100 cells/mm3 will be considered for enrollment following discussion and agreement between the Investigator and the Sponsor.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• matching placebo

• Bevirimat

Locations

Country	Name	City	State
United States	AIDS Research Consortium of Atlanta, Inc.	Atlanta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	The Research Insitute	Boston	Massachusetts
United States	UNC at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Southwest Infectious Diseases	Dallas	Texas
United States	University of Colorado Health Science Center	Denver	Colorado
United States	Gary Richmond	Fort Lauderdale	Florida
United States	University of Texas Medical Branch Internal Medicine	Galveston	Texas
United States	UCLA Medical Center	Los Angeles	California
United States	Orlando Immunology Center	Orlando	Florida
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Miriam Hospital/Brown University	Providence	Rhode Island
United States	Quest Clinical Research	San Francisco	California
United States	George Washington University Medical Center	Washington	District of Columbia
United States	Whitman-Walker Clinic	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Myrexis Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HIV-1 RNA change from baseline over the first 14 days of study		14 days	No
Secondary	safety and tolerability; pharmacokinetics		14 days	Yes

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