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

This study has been completed.
Sponsor:
Information provided by:
Myrexis Inc.
ClinicalTrials.gov Identifier:
NCT00511368
First received: August 1, 2007
Last updated: January 15, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: matching placebo
Drug: Bevirimat
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Myrexis Inc.:

Primary Outcome Measures:
  • HIV-1 RNA change from baseline over the first 14 days of study [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • safety and tolerability; pharmacokinetics [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]

Enrollment: 92
Study Start Date: April 2006
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
placebo
Drug: matching placebo
Other Names:
  • PA103001-04
  • PA-457N
Experimental: 2
Bevirimat
Drug: matching placebo
Other Names:
  • PA103001-04
  • PA-457N
Drug: Bevirimat

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00511368

Locations
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90035
Quest Clinical Research
San Francisco, California, United States, 94115
United States, Colorado
University of Colorado Health Science Center
Denver, Colorado, United States, 80262
United States, District of Columbia
George Washington University Medical Center
Washington, District of Columbia, United States, 20037
Whitman-Walker Clinic
Washington, District of Columbia, United States, 20037
United States, Florida
Gary Richmond
Fort Lauderdale, Florida, United States, 33316
Orlando Immunology Center
Orlando, Florida, United States, 32803
United States, Georgia
AIDS Research Consortium of Atlanta, Inc.
Atlanta, Georgia, United States, 30308
United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Massachusetts
The Research Insitute
Boston, Massachusetts, United States, 02215
United States, North Carolina
UNC at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19102
United States, Rhode Island
Miriam Hospital/Brown University
Providence, Rhode Island, United States, 02906
United States, Texas
Central Texas Clinical Research
Austin, Texas, United States, 78705
Southwest Infectious Diseases
Dallas, Texas, United States, 75204
University of Texas Medical Branch Internal Medicine
Galveston, Texas, United States, 77210-4786
Sponsors and Collaborators
Myrexis Inc.
Investigators
Study Director: Andrew Beelen, M.D. Myrexis Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Andrew Beelen, M.D, Sr. Director Clinical Research, Myriad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00511368     History of Changes
Other Study ID Numbers: PA103001-04 Study 203
Study First Received: August 1, 2007
Last Updated: January 15, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Myrexis Inc.:
HIV
treatment experienced
AIDS

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014