A Pilot Study Of A Novel Treatment Regimen, Maraviroc + Ritonavir Boosted Atazanavir, In Treatment Naive HIV-Infected Patients

Phase 2

Completed

• Conditions: Human Immunodeficiency Virus-1
• Interventions: Drug: maraviroc

• Registration Number: NCT00827112
• Lead Sponsor: ViiV Healthcare

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-01-21
• Study First Submitted QC: 2009-01-21
• Study First Posted: 2009-01-22
• Study Start: 2009-03
• Primary Completion: 2010-07
• Study Completion: 2011-07
• Results First Submitted: 2011-07-11
• Results First Submitted QC: 2011-10-19
• Results First Posted: 2011-11-24
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-08
• Last Update Posted: 2012-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 129

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	maraviroc	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.
Arm A	maraviroc	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than 50 Copies/Milliliter (mL)	Week 48

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96	Baseline, Week 16, Week 24, Week 48, Week 96
Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA	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
Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA	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
Time-Averaged Difference (TAD) in log10 Viral Load	Week 16, Week 24, Week 48, Week 96	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	Baseline, Week 16, Week 24, Week 48, Week 96
Maximum Observed Plasma Concentration (Cmax) of Maraviroc	Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
Minimum Observed Plasma Concentration (Cmin) of Maraviroc	Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
Average Observed Plasma Concentration (Cavg) of Maraviroc	Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)	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).
Number of Participants With Genotypic Resistance	Week 96 or Time of treatment failure	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	Week 96 or Time of treatment failure	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.
HIV-1 RNA Levels at Baseline	Baseline
Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14	Baseline , 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.
Time to Loss of Virological Response (TLOVR)	Baseline through Week 96	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.
Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96	Baseline, Week 16, Week 24, Week 48, Week 96
Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay	Baseline to Week 96 or Time of treatment Failure	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.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇪🇸 Sevilla, Spain