Clinical trial NCT00496782: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Treatment Experienced
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2007-07-04
Enrollment: 16
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.

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.

Primary outcomes:
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
timeFrame: Baseline, Day 4, 7, 14
Secondary outcomes:
measure: Subjects Achieving HIV-1 RNA <400 Copies/mL
timeFrame: Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24
measure: Subjects Achieving HIV-1 RNA <50 Copies/mL
timeFrame: Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24
measure: Subjects With Virologic Failure
timeFrame: Baseline up to Week 24
measure: Time to Virologic Failure
timeFrame: Baseline up to Week 24
measure: Change in Lymphocyte Subset CD4 From Baseline
timeFrame: Day 1 (Baseline), Day 7, 14, 28 and Weeks 24
measure: Change in Lymphocyte Subset CD8 From Day 1
timeFrame: Day 1(Baseline), Day 7, 14, 28 and Weeks 24
measure: Change in Lymphocyte Subsets; CD4 and CD8 From Screening.
timeFrame: Screening (Day -14 to 0), Day 1.
measure: Change in Detectable Tropism From Screening
timeFrame: Screening (Day -21 to 0), Baseline.
measure: Change in Detectable Tropism From Baseline
timeFrame: Baseline, Day 15 and Week 24/End of Study/Discontinuation
measure: Change in Detectable Resistance (Genotype) and Susceptibility (Phenotype) to Drugs in the Regimen From Screening
timeFrame: Screening (Day -21), Baseline (Day 0), Day 14 (after addition of MVC to a failing regimen), Week 24, and time of Virologic Failure.
measure: Number of Subjects With Susceptibility to Maraviroc
timeFrame: Screening (Day -21 to 0), Day 14, Week 24
measure: 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
timeFrame: Screening (Day -21 to 0), Day 14, time of virologic failure, and Week 24
measure: Correlation of Mutations in gp160 and the V3 Loop and Decreased Susceptibility to Maraviroc
timeFrame: Screening (Day -21 to 0), Day 14, time of virologic failure, Week 24
Other outcomes:
Locations:
city: Miami
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Chicago
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Topeka
country: United States
facility: Pfizer Investigational Site
state: Kansas
city: Topeka
country: United States
facility: Pfizer Investigational Site
state: Kansas
city: Detroit
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Omaha
country: United States
facility: Pfizer Investigational Site
state: Nebraska
city: Buffalo
country: United States
facility: Pfizer Investigational Site
state: New York
city: Tulsa
country: United States
facility: Pfizer Investigational Site
state: Oklahoma
city: Hampton
country: United States
facility: Pfizer Investigational Site
state: Virginia
city: Montreal
country: Canada
facility: Pfizer Investigational Site
state: Quebec
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: