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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
matching placebo
Bevirimat
Sponsored by
Myrexis Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, treatment experienced, AIDS

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCLA Medical Center
  • Quest Clinical Research
  • University of Colorado Health Science Center
  • George Washington University Medical Center
  • Whitman-Walker Clinic
  • Gary Richmond
  • Orlando Immunology Center
  • AIDS Research Consortium of Atlanta, Inc.
  • Northwestern University Feinberg School of Medicine
  • The Research Insitute
  • UNC at Chapel Hill
  • University Hospitals of Cleveland
  • Ohio State University Medical Center
  • Drexel University College of Medicine
  • Miriam Hospital/Brown University
  • Central Texas Clinical Research
  • Southwest Infectious Diseases
  • University of Texas Medical Branch Internal Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

1

2

Arm Description

placebo

Bevirimat

Outcomes

Primary Outcome Measures

HIV-1 RNA change from baseline over the first 14 days of study

Secondary Outcome Measures

safety and tolerability; pharmacokinetics

Full Information

First Posted
August 1, 2007
Last Updated
January 15, 2010
Sponsor
Myrexis Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00511368
Brief Title
Phase 2 Safety and Efficacy Study of Bevirimat Functional Monotherapy in HIV Treatment-Experienced Patients for 2 Weeks*
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2010
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
July 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Myrexis Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV, treatment experienced, AIDS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
92 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Placebo Comparator
Arm Description
placebo
Arm Title
2
Arm Type
Experimental
Arm Description
Bevirimat
Intervention Type
Drug
Intervention Name(s)
matching placebo
Other Intervention Name(s)
PA103001-04, PA-457N
Intervention Type
Drug
Intervention Name(s)
Bevirimat
Primary Outcome Measure Information:
Title
HIV-1 RNA change from baseline over the first 14 days of study
Time Frame
14 days
Secondary Outcome Measure Information:
Title
safety and tolerability; pharmacokinetics
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Beelen, M.D.
Organizational Affiliation
Myrexis Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90035
Country
United States
Facility Name
Quest Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Colorado Health Science Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
George Washington University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Whitman-Walker Clinic
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Gary Richmond
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33316
Country
United States
Facility Name
Orlando Immunology Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
AIDS Research Consortium of Atlanta, Inc.
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
The Research Insitute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
UNC at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
University Hospitals of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Drexel University College of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19102
Country
United States
Facility Name
Miriam Hospital/Brown University
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
Central Texas Clinical Research
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Southwest Infectious Diseases
City
Dallas
State/Province
Texas
ZIP/Postal Code
75204
Country
United States
Facility Name
University of Texas Medical Branch Internal Medicine
City
Galveston
State/Province
Texas
ZIP/Postal Code
77210-4786
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.hivforum.org
Description
Related Info
URL
http://www.projectinform.org
Description
Related Info
URL
http://www.amfar.org
Description
Related Info
URL
http://www.hivandhepatitis.com
Description
Related Info
URL
http://www.medscape.com
Description
Related Info

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

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