Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been terminated.
(See Detailed Description)
Sponsor:
Collaborator:
Pfizer
Information provided by:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00496782
First received: July 3, 2007
Last updated: November 10, 2010
Last verified: March 2010

July 3, 2007
November 10, 2010
July 2007
October 2008   (final data collection date for primary outcome measure)
Change From Baseline in Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) With R5 & Non-R5 Tropism Results From the Trofile(tm) Assay [ Time Frame: Baseline, Day 4, 7, 14 ] [ Designated as safety issue: No ]
Spearman's correlation coefficient to assess percentage of participants achieving HIV-1 RNA with tropism
The primary objective of this pilot study is to determine whether there is a correlation between viral load reduction (at Day 7 or 14) following a short course (14 days) ofmaraviroc added to a failing regimen, and the results of the TrofileTM assay.
Complete list of historical versions of study NCT00496782 on ClinicalTrials.gov Archive Site
  • Subjects Achieving HIV-1 RNA <400 Copies/mL [ Time Frame: Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24 ] [ Designated as safety issue: Yes ]
    Number of Subjects Achieving HIV-1 RNA <400 Copies/mL at each time point
  • Subjects Achieving HIV-1 RNA <50 Copies/mL [ Time Frame: Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24 ] [ Designated as safety issue: Yes ]
    Number of Subjects Achieving HIV-1 RNA <50 Copies/mL at each time point
  • Subjects With Virologic Failure [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (Baseline), Day 7, 14, 28 and Weeks 24 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1(Baseline), Day 7, 14, 28 and Weeks 24 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Screening (Day -14 to 0), Day 1. ] [ Designated as safety issue: No ]
    Calculated avergae of {CD4 or CD8 at Day 1 - CD4 or CD8 at Screening}
  • Change in Detectable Tropism From Screening [ Time Frame: Screening (Day -21 to 0), Baseline. ] [ Designated as safety issue: No ]
    Number of subjects who switch their tropism status from screening to Baseline
  • Change in Detectable Tropism From Baseline [ Time Frame: Baseline, Day 15 and Week 24/End of Study/Discontinuation ] [ Designated as safety issue: No ]
    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 [ 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. ] [ Designated as safety issue: No ]
    Change in detectable resistance (genotype) and susceptibility (phenotype) to drugs in the regimen from Screening
  • Number of Subjects With Susceptibility to Maraviroc [ Time Frame: Screening (Day -21 to 0), Day 14, Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Screening (Day -21 to 0), Day 14, time of virologic failure, and Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Screening (Day -21 to 0), Day 14, time of virologic failure, Week 24 ] [ Designated as safety issue: No ]
  • Safety and tolerability.
  • Proportion of subjects achieving HIV RNA <400 and <50 copies/mL at all time points of the study.Time to virologic failure (see section 6.5.1).
  • Change in lymphocyte subsets; CD4 and CD8 (count and percent) from Screeningvisit (Day -14 to 0) to Day 1.Change in lymphocyte subsets; CD4 and CD8 (count and percent) from Day 1 to Day 7, 14, 28 and Weeks 24.
  • Change in detectable resistance(genotype) and susceptibility(phenotype) to drugs in the regimen [ Time Frame: From Screening visit(Day -14 to 0)to Day 1, 14 and time of virologic failure and possibly at Day 7, 28 and Week 12 and 24 for all subjects with HIV RNA >1000 copies/mL. ]
  • Change in gene sequence in gp-160, and the V3 loop from Screening visit (Day -14 to 0) to Day 14 and time of virologic failure (see section 6.5.1), week 24 and possibly at Day 7, 28, and Week 12 for all subjects with HIV RNA >1000 copies/mL.
  • Change in phenotypic susceptibility to maraviroc (IC50 and presence of plateaus) [ Time Frame: From Screening visit (Day -14 to 0) to Day 1, 14 and time of virologic failure and possibly at Day 7, 28, Week 12 and 24 for all subjects with HIV RNA >1000 copies/mL. ]
  • Correlation of mutations in gp160 and the V3 loop and decreased susceptibility to maraviroc (IC50 and/or presence of plateaus).
  • Change in detectable tropism from Screening visit (Day -14 to 0) to Day 1.
  • Change in detectable tropism from Day 1 to Day 7, 14, 28 and Week 8, 12, 18, and 24
Not Provided
Not Provided
 
Multicenter Pilot Study To Define The Marker As An Alternate For Tropism Assay
Surrogate Marker For Tropism-A Multi-Center, Open Label, Pilot Study

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Screening
HIV Infections
  • Drug: maraviroc
    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.
  • Procedure: Trofile Assay and HIV RNA quantification assay
    Trofile Assay and HIV RNA quantification assay
Single
Interventions:
  • Drug: maraviroc
  • Procedure: Trofile Assay and HIV RNA quantification assay
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
16
October 2008
October 2008   (final data collection date for primary outcome measure)

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.
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00496782
A4001060
No
Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ViiV Healthcare
Pfizer
Study Director: Pfizer CT.gov Call Center Pfizer
ViiV Healthcare
March 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP