Back to resultsA Pilot Study Of A Novel Treatment Regimen, Maraviroc + Ritonavir Boosted Atazanavir, In Treatment Naive HIV-Infected Patients
Primary Purpose
Human Immunodeficiency Virus-1
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
maraviroc
maraviroc
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus-1 focused on measuring CCR5-tropic HIV-1 virus
Eligibility Criteria
Inclusion Criteria:
- HIV-1 RNA viral load of ≥1,000 copies/mL measured at the Screening Visit.
- CD4 count ≥100 cells/mm3 at Screening.
- Have only R5 HIV-1 at Screening as verified by the Monogram Bioscience Trofile® assay with enhanced sensitivity.
Exclusion Criteria:
- Prior treatment with any other HIV antiretroviral therapy for more than 14 days at any time.
- Any evidence of resistance to atazanavir, tenofovir, and emtricitabine.
- X4-or dual/mixed-tropic virus by enhanced Trofile assay or repeated assay failure or not reportable results.
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
- 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
- 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
- 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 2
Arm Type
Experimental
Experimental
Arm Label
Arm A
Arm B
Arm Description
maraviroc (Selzentry, Celsentri) 150 mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100mg QD Subjects experiencing unconjugated hyperbilirubinemia attributable to atazanavir (Reyataz) /ritonavir (Norvir) without any other etiology of hyperbilirubinemia, responding to the therapy without virologic failure, but expressing cosmetic concerns because of the jaundice or scleral icterus (associated with bilirubin elevations) and wish to discontinue atazanavir (Reyataz) in spite of reassurances by the investigator, will be permitted on a single occasion only to switch to another protease inhibitor either darunavir (Prezista)/ritonavir (Norvir)((800/100 mg) QD or lopinavir/ritonavir (Kaletra, Aluvia)(400/100mg) BID and remain in the study. If the investigator decides to switch to a protease inhibitor other than darunavir (Prezista)/ritonavir (Norvir) or lopinavir/ritonavir (Kaletra, Aluvia)(, then the subject must be discontinued from the study.
emtricitabine/tenofovir (Truvada) 200/300mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100 mg QD Subjects experiencing unconjugated hyperbilirubinemia attributable to atazanavir (Reyataz) /ritonavir (Norvir) without any other etiology of hyperbilirubinemia, responding to the therapy without virologic failure, but expressing cosmetic concerns because of the jaundice or scleral icterus (associated with bilirubin elevations) and wish to discontinue atazanavir in spite of reassurances by the investigator, will be permitted on a single occasion only to switch to another protease inhibitor either darunavir/ritonavir (800/100 mg) QD or lopinavir/ritonavir (400/100mg) BID and remain in the study. If the investigator decides to switch to a protease inhibitor other than darunavir/ritonavir or lopinavir/ritonavir, then the subject must be discontinued from the study.
Outcomes
Primary Outcome Measures
Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than 50 Copies/Milliliter (mL)
Secondary Outcome Measures
HIV-1 RNA Levels at Baseline
Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14
Plasma HIV-1 RNA levels were evaluated for first 15 participants enrolled at United States (U.S) sites only.
Maximum Observed Plasma Concentration (Cmax) of Maraviroc
Minimum Observed Plasma Concentration (Cmin) of Maraviroc
Average Observed Plasma Concentration (Cavg) of Maraviroc
Cavg was described as area under the plasma concentration-time profile from time zero to time 24 hours (AUC24) divided by the dosing interval (AUC24/ 24).
Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96
Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA
Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA
Time to Loss of Virological Response (TLOVR)
TLOVR (virological failure) was defined as the time from first dose of study treatment (Day 1) until the time of virologic failure using the time to loss of virologic response algorithm.
Time-Averaged Difference (TAD) in log10 Viral Load
TAD was calculated as area under the curve of HIV divided by time period minus baseline HIV where HIV was denoted as HIV-1 RNA (log10 copies/mL).
Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96
Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96
Number of Participants With Genotypic Resistance
Genotypic resistance was assessed for all participants at screening and was evaluated for protease inhibitors (PIs), Nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs) using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96.
Number of Participants With Phenotypic Resistance
Phenotypic resistance was assessed for all participants at screening and was evaluated for PIs, NRTIs, and NNRTIs using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96.
Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay
Viral tropism was determined using the trofile assay with enhanced sensitivity for participants with HIV-1 RNA greater than equal to 1000 copies/mL. The enhanced trofile assay had the sensitivity to detect 100 percent of spiked samples when C-X-C chemokine receptor type 4 {CXCR4} [X4]-using HIV-1 RNA represented 0.3 percent of the total viral population.
Full Information
NCT ID
NCT00827112
First Posted
January 21, 2009
Last Updated
June 8, 2012
Sponsor
ViiV Healthcare
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT00827112
Brief Title
A Pilot Study Of A Novel Treatment Regimen, Maraviroc + Ritonavir Boosted Atazanavir, In Treatment Naive HIV-Infected Patients
Official Title
Pilot Study Of Novel Combination Of Maraviroc + Atazanavir/Ritonavir vs. Atazanavir/Ritonavir + Emtricitabine/Tenofovir For The Treatment Of Naïve HIV-Infected Patients With R5 HIV-1
Study Type
Interventional
2. Study Status
Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ViiV Healthcare
Collaborators
Pfizer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a pilot study to examine if the novel treatment regimen maraviroc plus boosted atazanavir can be expected to be safe and efficacious in treatment naive HIV infected patients. Based on the results from this study, a confirmatory phase 3 study may be conducted.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus-1
Keywords
CCR5-tropic HIV-1 virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
129 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
maraviroc (Selzentry, Celsentri) 150 mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100mg QD Subjects experiencing unconjugated hyperbilirubinemia attributable to atazanavir (Reyataz) /ritonavir (Norvir) without any other etiology of hyperbilirubinemia, responding to the therapy without virologic failure, but expressing cosmetic concerns because of the jaundice or scleral icterus (associated with bilirubin elevations) and wish to discontinue atazanavir (Reyataz) in spite of reassurances by the investigator, will be permitted on a single occasion only to switch to another protease inhibitor either darunavir (Prezista)/ritonavir (Norvir)((800/100 mg) QD or lopinavir/ritonavir (Kaletra, Aluvia)(400/100mg) BID and remain in the study. If the investigator decides to switch to a protease inhibitor other than darunavir (Prezista)/ritonavir (Norvir) or lopinavir/ritonavir (Kaletra, Aluvia)(, then the subject must be discontinued from the study.
Arm Title
Arm B
Arm Type
Experimental
Arm Description
emtricitabine/tenofovir (Truvada) 200/300mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100 mg QD
Subjects experiencing unconjugated hyperbilirubinemia attributable to atazanavir (Reyataz) /ritonavir (Norvir) without any other etiology of hyperbilirubinemia, responding to the therapy without virologic failure, but expressing cosmetic concerns because of the jaundice or scleral icterus (associated with bilirubin elevations) and wish to discontinue atazanavir in spite of reassurances by the investigator, will be permitted on a single occasion only to switch to another protease inhibitor either darunavir/ritonavir (800/100 mg) QD or lopinavir/ritonavir (400/100mg) BID and remain in the study. If the investigator decides to switch to a protease inhibitor other than darunavir/ritonavir or lopinavir/ritonavir, then the subject must be discontinued from the study.
Intervention Type
Drug
Intervention Name(s)
maraviroc
Other Intervention Name(s)
maraviroc =Celsentri, Selzentry; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia; darunavir=Prezista
Intervention Description
maraviroc (Selzentry, Celsentri) 150mg QD + atazanavir (Reyataz) /ritonavir (Norvir) (300/100mg) QD OR maraviroc (Selzentry, Celsentri) 150mg QD+ darunavir (Prezista)/ritonavir (Norvir) (800/100 mg) QD (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by darunavir (Prezista)/ritonavir (Norvir)) OR maraviroc (Selzentry, Celsentri) 150mg QD+ lopinavir/ritonavir (Kaletra, Aluvia) (400/100 mg) BID (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by lopinavir/ritonavir (Kaletra, Aluvia))
Intervention Type
Drug
Intervention Name(s)
maraviroc
Other Intervention Name(s)
maraviroc=Celsentri, Selzentry; emtricitabine/tenofovir=Truvada; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia
Intervention Description
emtricitabine/tenofovir (Truvada) 200/300mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100 mg QD OR emtricitabine/tenofovir (Truvada) 200/300 mg QD + darunavir (Prezista)/ritonavir (Norvir) (800/100 mg) QD (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by darunavir (Prezista)/ritonavir (Norvir)) OR emtricitabine/tenofovir (Truvada) 200/300 mg QD + lopinavir/ritonavir(Kaletra, Aluvia) (400/100 mg) BID (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by lopinavir/ritonavir (Kaletra, Aluvia))
Primary Outcome Measure Information:
Title
Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than 50 Copies/Milliliter (mL)
Time Frame
Week 48
Secondary Outcome Measure Information:
Title
HIV-1 RNA Levels at Baseline
Time Frame
Baseline
Title
Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14
Description
Plasma HIV-1 RNA levels were evaluated for first 15 participants enrolled at United States (U.S) sites only.
Time Frame
Baseline , Days 4, 7, 10 and 14
Title
Maximum Observed Plasma Concentration (Cmax) of Maraviroc
Time Frame
Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
Title
Minimum Observed Plasma Concentration (Cmin) of Maraviroc
Time Frame
Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
Title
Average Observed Plasma Concentration (Cavg) of Maraviroc
Description
Cavg was described as area under the plasma concentration-time profile from time zero to time 24 hours (AUC24) divided by the dosing interval (AUC24/ 24).
Time Frame
Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
Title
Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96
Time Frame
Baseline, Week 16, Week 24, Week 48, Week 96
Title
Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA
Time Frame
Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, Week 96
Title
Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA
Time Frame
Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, Week 96
Title
Time to Loss of Virological Response (TLOVR)
Description
TLOVR (virological failure) was defined as the time from first dose of study treatment (Day 1) until the time of virologic failure using the time to loss of virologic response algorithm.
Time Frame
Baseline through Week 96
Title
Time-Averaged Difference (TAD) in log10 Viral Load
Description
TAD was calculated as area under the curve of HIV divided by time period minus baseline HIV where HIV was denoted as HIV-1 RNA (log10 copies/mL).
Time Frame
Week 16, Week 24, Week 48, Week 96
Title
Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96
Time Frame
Baseline, Week 16, Week 24, Week 48, Week 96
Title
Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96
Time Frame
Baseline, Week 16, Week 24, Week 48, Week 96
Title
Number of Participants With Genotypic Resistance
Description
Genotypic resistance was assessed for all participants at screening and was evaluated for protease inhibitors (PIs), Nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs) using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96.
Time Frame
Week 96 or Time of treatment failure
Title
Number of Participants With Phenotypic Resistance
Description
Phenotypic resistance was assessed for all participants at screening and was evaluated for PIs, NRTIs, and NNRTIs using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96.
Time Frame
Week 96 or Time of treatment failure
Title
Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay
Description
Viral tropism was determined using the trofile assay with enhanced sensitivity for participants with HIV-1 RNA greater than equal to 1000 copies/mL. The enhanced trofile assay had the sensitivity to detect 100 percent of spiked samples when C-X-C chemokine receptor type 4 {CXCR4} [X4]-using HIV-1 RNA represented 0.3 percent of the total viral population.
Time Frame
Baseline to Week 96 or Time of treatment Failure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
HIV-1 RNA viral load of ≥1,000 copies/mL measured at the Screening Visit.
CD4 count ≥100 cells/mm3 at Screening.
Have only R5 HIV-1 at Screening as verified by the Monogram Bioscience Trofile® assay with enhanced sensitivity.
Exclusion Criteria:
Prior treatment with any other HIV antiretroviral therapy for more than 14 days at any time.
Any evidence of resistance to atazanavir, tenofovir, and emtricitabine.
X4-or dual/mixed-tropic virus by enhanced Trofile assay or repeated assay failure or not reportable results.
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
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Pfizer Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90028
Country
United States
Facility Name
Pfizer Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Pfizer Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90069
Country
United States
Facility Name
Pfizer Investigational Site
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06851
Country
United States
Facility Name
Pfizer Investigational Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20009
Country
United States
Facility Name
Pfizer Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33133
Country
United States
Facility Name
Pfizer Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Pfizer Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33137
Country
United States
Facility Name
Pfizer Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Pfizer Investigational Site
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
Pfizer Investigational Site
City
St. Petersburg
State/Province
Florida
ZIP/Postal Code
33713
Country
United States
Facility Name
Pfizer Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33602
Country
United States
Facility Name
Pfizer Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
Pfizer Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30312
Country
United States
Facility Name
Pfizer Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60657
Country
United States
Facility Name
Pfizer Investigational Site
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01107
Country
United States
Facility Name
Pfizer Investigational Site
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
Pfizer Investigational Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Pfizer Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68106
Country
United States
Facility Name
Pfizer Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Pfizer Investigational Site
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Pfizer Investigational Site
City
Addison
State/Province
Texas
ZIP/Postal Code
75001
Country
United States
Facility Name
Pfizer Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75204
Country
United States
Facility Name
Pfizer Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Pfizer Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77098
Country
United States
Facility Name
Pfizer Investigational Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Pfizer Investigational Site
City
Berlin
ZIP/Postal Code
10243
Country
Germany
Facility Name
Pfizer Investigational Site
City
Berlin
ZIP/Postal Code
12157
Country
Germany
Facility Name
Pfizer Investigational Site
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Pfizer Investigational Site
City
Hamburg
ZIP/Postal Code
20146
Country
Germany
Facility Name
Pfizer Investigational Site
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Pfizer Investigational Site
City
Muenchen
ZIP/Postal Code
80335
Country
Germany
Facility Name
Pfizer Investigational Site
City
L'hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Pfizer Investigational Site
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
Pfizer Investigational Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Pfizer Investigational Site
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Pfizer Investigational Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Pfizer Investigational Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A4001078&StudyName=A%20Pilot%20Study%20Of%20A%20Novel%20Treatment%20Regimen%2C%20Maraviroc%20+%20Ritonavir%20Boosted%20Atazanavir%2C%20In%20Treatment%20Naive%20HIV-Infected%20Patients
Description
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A Pilot Study Of A Novel Treatment Regimen, Maraviroc + Ritonavir Boosted Atazanavir, In Treatment Naive HIV-Infected Patients
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