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Multicenter Pilot Study To Define The Marker As An Alternate For Tropism Assay

Primary Purpose

HIV Infections

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
maraviroc
Trofile Assay and HIV RNA quantification assay
Sponsored by
ViiV Healthcare
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional screening trial for HIV Infections focused on measuring Treatment Experienced

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • ≥ 16 years of age (or minimum adult age as determined by local regulatory authorities or as dictated by local law) at the screening visit.
  • Have an HIV RNA ≥ 1000 copies/mL, at screening.
  • Subjects receiving another investigational antiretroviral compound through participation in a phase 3 or 4 clinical study are eligible to participate in this trial provided.
  • That the 2 investigational agents are required to offer the subject a regimen with 2 or 3 active antiretroviral drugs (i.e. one or fewer approved treatment is available to the subject due to prior resistance or intolerance),
  • Neither protocol prohibits the use of the other antiretroviral agent, AND the dosing of the two agents when used together is known AND a letter from the Pfizer clinical pharmacologists for maraviroc identifies the dose of maraviroc to be used with other investigational agents.
  • Based on screening genotypic resistance testing results the subject must be able to receive at least 3 active drugs other than maraviroc in the new OBT. This is defined as:
  • Having three drugs considered susceptible by genotype interpretation (if etravirine will be used, fewer than 3 etravirine resistance mutations will be taken as etravirine susceptibility); or,
  • Having two drugs considered susceptible by genotype interpretation (if etravirine will be used, fewer than 3 etravirine resistance mutations will be taken as etravirine susceptibility) and be willing to include raltegravir in the OBT not having used raltegravir in the past.

Exclusion Criteria:

  • Potentially life threatening (Grade 4) laboratory abnormality or medical condition.
  • Severe hepatic impairment (Child-Pugh classification B or C).
  • End stage renal disease or other disease states requiring dialysis therapy.

Sites / Locations

  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Single

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) With R5 & Non-R5 Tropism Results From the Trofile(tm) Assay
Spearman's correlation coefficient to assess percentage of participants achieving HIV-1 RNA with tropism

Secondary Outcome Measures

Subjects Achieving HIV-1 RNA <400 Copies/mL
Number of Subjects Achieving HIV-1 RNA <400 Copies/mL at each time point
Subjects Achieving HIV-1 RNA <50 Copies/mL
Number of Subjects Achieving HIV-1 RNA <50 Copies/mL at each time point
Subjects With Virologic Failure
For this protocol, virologic failure will be confirmed by a repeat viral load test within 2 weeks of first viral load meeting any of the following criteria: 1. Failing to achieve a reduction in HIV-1 RNA > 0.5 log10 copies/mL from baseline by the second viral load determination (unless the viral load is below level of quantification [LOQ]); 2. Experiencing a > 0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from baseline > 0.5 log10 copies/mL; or 3. Experiencing an HIV-1 RNA >1000 copies/mL after having achieved an HIV-1 RNA below LOQ.
Time to Virologic Failure
For this protocol, virologic failure will be confirmed by a repeat viral load test within 2 weeks of first viral load meeting any of the following criteria: 1. Failing to achieve a reduction in HIV-1 RNA > 0.5 log10 copies/mL from baseline by the second viral load determination (unless the viral load is below level of quantification [LOQ]); 2. Experiencing a > 0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from baseline > 0.5 log10 copies/mL; or 3. Experiencing an HIV-1 RNA >1000 copies/mL after having achieved an HIV-1 RNA below LOQ.
Change in Lymphocyte Subset CD4 From Baseline
Calculated average of CD4 at Day 7, 14, 28 and Week 24 minus CD4 at Day 1
Change in Lymphocyte Subset CD8 From Day 1
Calculated average of CD8 at Day 7, 14, 28 and Week 24 minus CD8 at Day 1
Change in Lymphocyte Subsets; CD4 and CD8 From Screening.
Calculated avergae of {CD4 or CD8 at Day 1 - CD4 or CD8 at Screening}
Change in Detectable Tropism From Screening
Number of subjects who switch their tropism status from screening to Baseline
Change in Detectable Tropism From Baseline
Number of subjects who switch their tropism status from Baseline to Days 7, 14, and Week 24/End of Study(EOS)/Discontinuation
Change in Detectable Resistance (Genotype) and Susceptibility (Phenotype) to Drugs in the Regimen From Screening
Change in detectable resistance (genotype) and susceptibility (phenotype) to drugs in the regimen from Screening
Number of Subjects With Susceptibility to Maraviroc
Phenotypic susceptibility to maraviroc
Change in Gene Sequence in Gp-160, and the V3 Loop From Screening Visit (Day -21 to 0) to Day 14, Time of Virologic Failure (See Section 6.5.1) and Week 24
Change in gene sequence in gp-160, and the V3 loop from Screening visit (Day -21 to 0) to Day 14, time of virologic failure (See Section 6.5.1) and Week 24
Correlation of Mutations in gp160 and the V3 Loop and Decreased Susceptibility to Maraviroc

Full Information

First Posted
July 3, 2007
Last Updated
January 9, 2019
Sponsor
ViiV Healthcare
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00496782
Brief Title
Multicenter Pilot Study To Define The Marker As An Alternate For Tropism Assay
Official Title
Surrogate Marker For Tropism-A Multi-Center, Open Label, Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Terminated
Why Stopped
See Detailed Description
Study Start Date
July 2007 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ViiV Healthcare
Collaborators
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this pilot study is to determine whether there is a correlation between viral load reduction (at Day 4, 7 or 14) following a short course (14 days) of Maraviroc added to a failing regimen, and the R5 result of the TrofileTM assay at screening.
Detailed Description
The study A4001060 has been discontinued on April 22, 2008. A review of the poor rate of enrollment has projected difficulties in completing the study in a timely manner, despite the best efforts by the sponsor and the sites. Given the difficulties encountered in this pilot study and the need to conduct an even larger confirmatory study, the decision to discontinue the study has therefore been made. It should be noted that safety concerns have not been seen in this study and have not factored into this decision.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Treatment Experienced

7. Study Design

Primary Purpose
Screening
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single
Arm Type
Other
Intervention Type
Drug
Intervention Name(s)
maraviroc
Intervention Description
Treatment-experienced subjects on failed therapy, with HIV RNA ≥ 1000 copies/mL, are eligible who will receive a tropism assay at screening (Day -14 to 0). Subjects who are eligible will receive maraviroc added to a failing regimen from Day 1 to 14. On day 15, subjects will discontinue the current treatment regimen and begin a new OBT. Subjects with only R5 HIV will continue receiving maraviroc plus OBT. Subjects with non-R5 virus will discontinue receiving maraviroc but continue to receive the new OBT. Investigator selects OBT based on results of phenotype/genotype testing at baseline. The nominal dose for maraviroc is 300 mg BID. The maraviroc dose should be adjusted based on OBT patient is taking. If OBT includes CYP3A4 inhibitor (with or without inducers) maraviroc dose should be 150 mg BID and if OBT includes CYP3A4 inducer (without inhibitors) maraviroc dose should be 600mg BID. If OBT does not include any CYP3A4 inducers or inhibitors maraviroc dose should be 300 mg BID.
Intervention Type
Procedure
Intervention Name(s)
Trofile Assay and HIV RNA quantification assay
Intervention Description
Trofile Assay and HIV RNA quantification assay
Primary Outcome Measure Information:
Title
Change From Baseline in Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) With R5 & Non-R5 Tropism Results From the Trofile(tm) Assay
Description
Spearman's correlation coefficient to assess percentage of participants achieving HIV-1 RNA with tropism
Time Frame
Baseline, Day 4, 7, 14
Secondary Outcome Measure Information:
Title
Subjects Achieving HIV-1 RNA <400 Copies/mL
Description
Number of Subjects Achieving HIV-1 RNA <400 Copies/mL at each time point
Time Frame
Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24
Title
Subjects Achieving HIV-1 RNA <50 Copies/mL
Description
Number of Subjects Achieving HIV-1 RNA <50 Copies/mL at each time point
Time Frame
Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24
Title
Subjects With Virologic Failure
Description
For this protocol, virologic failure will be confirmed by a repeat viral load test within 2 weeks of first viral load meeting any of the following criteria: 1. Failing to achieve a reduction in HIV-1 RNA > 0.5 log10 copies/mL from baseline by the second viral load determination (unless the viral load is below level of quantification [LOQ]); 2. Experiencing a > 0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from baseline > 0.5 log10 copies/mL; or 3. Experiencing an HIV-1 RNA >1000 copies/mL after having achieved an HIV-1 RNA below LOQ.
Time Frame
Baseline up to Week 24
Title
Time to Virologic Failure
Description
For this protocol, virologic failure will be confirmed by a repeat viral load test within 2 weeks of first viral load meeting any of the following criteria: 1. Failing to achieve a reduction in HIV-1 RNA > 0.5 log10 copies/mL from baseline by the second viral load determination (unless the viral load is below level of quantification [LOQ]); 2. Experiencing a > 0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from baseline > 0.5 log10 copies/mL; or 3. Experiencing an HIV-1 RNA >1000 copies/mL after having achieved an HIV-1 RNA below LOQ.
Time Frame
Baseline up to Week 24
Title
Change in Lymphocyte Subset CD4 From Baseline
Description
Calculated average of CD4 at Day 7, 14, 28 and Week 24 minus CD4 at Day 1
Time Frame
Day 1 (Baseline), Day 7, 14, 28 and Weeks 24
Title
Change in Lymphocyte Subset CD8 From Day 1
Description
Calculated average of CD8 at Day 7, 14, 28 and Week 24 minus CD8 at Day 1
Time Frame
Day 1(Baseline), Day 7, 14, 28 and Weeks 24
Title
Change in Lymphocyte Subsets; CD4 and CD8 From Screening.
Description
Calculated avergae of {CD4 or CD8 at Day 1 - CD4 or CD8 at Screening}
Time Frame
Screening (Day -14 to 0), Day 1.
Title
Change in Detectable Tropism From Screening
Description
Number of subjects who switch their tropism status from screening to Baseline
Time Frame
Screening (Day -21 to 0), Baseline.
Title
Change in Detectable Tropism From Baseline
Description
Number of subjects who switch their tropism status from Baseline to Days 7, 14, and Week 24/End of Study(EOS)/Discontinuation
Time Frame
Baseline, Day 15 and Week 24/End of Study/Discontinuation
Title
Change in Detectable Resistance (Genotype) and Susceptibility (Phenotype) to Drugs in the Regimen From Screening
Description
Change in detectable resistance (genotype) and susceptibility (phenotype) to drugs in the regimen from Screening
Time Frame
Screening (Day -21), Baseline (Day 0), Day 14 (after addition of MVC to a failing regimen), Week 24, and time of Virologic Failure.
Title
Number of Subjects With Susceptibility to Maraviroc
Description
Phenotypic susceptibility to maraviroc
Time Frame
Screening (Day -21 to 0), Day 14, Week 24
Title
Change in Gene Sequence in Gp-160, and the V3 Loop From Screening Visit (Day -21 to 0) to Day 14, Time of Virologic Failure (See Section 6.5.1) and Week 24
Description
Change in gene sequence in gp-160, and the V3 loop from Screening visit (Day -21 to 0) to Day 14, time of virologic failure (See Section 6.5.1) and Week 24
Time Frame
Screening (Day -21 to 0), Day 14, time of virologic failure, and Week 24
Title
Correlation of Mutations in gp160 and the V3 Loop and Decreased Susceptibility to Maraviroc
Time Frame
Screening (Day -21 to 0), Day 14, time of virologic failure, Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥ 16 years of age (or minimum adult age as determined by local regulatory authorities or as dictated by local law) at the screening visit. Have an HIV RNA ≥ 1000 copies/mL, at screening. Subjects receiving another investigational antiretroviral compound through participation in a phase 3 or 4 clinical study are eligible to participate in this trial provided. That the 2 investigational agents are required to offer the subject a regimen with 2 or 3 active antiretroviral drugs (i.e. one or fewer approved treatment is available to the subject due to prior resistance or intolerance), Neither protocol prohibits the use of the other antiretroviral agent, AND the dosing of the two agents when used together is known AND a letter from the Pfizer clinical pharmacologists for maraviroc identifies the dose of maraviroc to be used with other investigational agents. Based on screening genotypic resistance testing results the subject must be able to receive at least 3 active drugs other than maraviroc in the new OBT. This is defined as: Having three drugs considered susceptible by genotype interpretation (if etravirine will be used, fewer than 3 etravirine resistance mutations will be taken as etravirine susceptibility); or, Having two drugs considered susceptible by genotype interpretation (if etravirine will be used, fewer than 3 etravirine resistance mutations will be taken as etravirine susceptibility) and be willing to include raltegravir in the OBT not having used raltegravir in the past. Exclusion Criteria: Potentially life threatening (Grade 4) laboratory abnormality or medical condition. Severe hepatic impairment (Child-Pugh classification B or C). End stage renal disease or other disease states requiring dialysis therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33137
Country
United States
Facility Name
Pfizer Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60613
Country
United States
Facility Name
Pfizer Investigational Site
City
Topeka
State/Province
Kansas
ZIP/Postal Code
66606-1670
Country
United States
Facility Name
Pfizer Investigational Site
City
Topeka
State/Province
Kansas
ZIP/Postal Code
66606
Country
United States
Facility Name
Pfizer Investigational Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Pfizer Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-5400
Country
United States
Facility Name
Pfizer Investigational Site
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Pfizer Investigational Site
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74135
Country
United States
Facility Name
Pfizer Investigational Site
City
Hampton
State/Province
Virginia
ZIP/Postal Code
23666
Country
United States
Facility Name
Pfizer Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 5B1
Country
Canada

12. IPD Sharing Statement

Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A4001060&StudyName=Multicenter%20Pilot%20Study%20To%20Define%20The%20Marker%20As%20An%20Alternate%20For%20Tropism%20Assay
Description
To obtain contact information for a study center near you, click here.

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Multicenter Pilot Study To Define The Marker As An Alternate For Tropism Assay

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