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

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

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.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus-1
• Intervention / Treatment: Drug: maraviroc; Drug: maraviroc

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12157
    • Pfizer Investigational Site
  • Berlin, Germany, 10243
    • Pfizer Investigational Site
  • Frankfurt am Main, Germany, 60590
    • Pfizer Investigational Site
  • Hamburg, Germany, 20146
    • Pfizer Investigational Site
  • Koeln, Germany, 50937
    • Pfizer Investigational Site
  • Muenchen, Germany, 80335
    • Pfizer Investigational Site
• Spain
  • Alicante, Spain, 03010
    • Pfizer Investigational Site
  • Barcelona, Spain, 08036
    • Pfizer Investigational Site
  • Cordoba, Spain, 14004
    • Pfizer Investigational Site
  • Madrid, Spain, 28046
    • Pfizer Investigational Site
  • Sevilla, Spain, 41013
    • Pfizer Investigational Site
  • Barcelona
    • L'hospitalet de Llobregat, Barcelona, Spain, 08907
      • Pfizer Investigational Site
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90069
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90027
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90028
      • Pfizer Investigational Site
  • Connecticut
    • Norwalk, Connecticut, United States, 06851
      • Pfizer Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Pfizer Investigational Site
  • Florida
    • Miami, Florida, United States, 33136
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33133
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33137
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32803
      • Pfizer Investigational Site
    • Pensacola, Florida, United States, 32504
      • Pfizer Investigational Site
    • St. Petersburg, Florida, United States, 33713
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33602
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33614
      • Pfizer Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Pfizer Investigational Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Pfizer Investigational Site
    • Springfield, Massachusetts, United States, 01199
      • Pfizer Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Pfizer Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10003
      • Pfizer Investigational Site
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Pfizer Investigational Site
  • Texas
    • Addison, Texas, United States, 75001
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75204
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75390
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77098
      • Pfizer Investigational Site
  • Washington
    • Spokane, Washington, United States, 99204
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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.	Drug: maraviroc; 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)); Other Names: maraviroc =Celsentri, Selzentry; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia; darunavir=Prezista; Drug: maraviroc; 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)); Other Names: maraviroc=Celsentri, Selzentry; emtricitabine/tenofovir=Truvada; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia
Experimental: Arm B; 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.	Drug: maraviroc; 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)); Other Names: maraviroc =Celsentri, Selzentry; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia; darunavir=Prezista; Drug: maraviroc; 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)); Other Names: maraviroc=Celsentri, Selzentry; emtricitabine/tenofovir=Truvada; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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	Plasma HIV-1 RNA levels were evaluated for first 15 participants enrolled at United States (U.S) sites only.	Baseline , Days 4, 7, 10 and 14
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	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).	Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
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 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
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
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.	Baseline through Week 96
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).	Week 16, Week 24, Week 48, Week 96
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
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 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.	Week 96 or Time of treatment failure
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.	Week 96 or Time of treatment failure
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.	Baseline to Week 96 or Time of treatment Failure

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: January 21, 2009
• First Submitted That Met QC Criteria: January 21, 2009
• First Posted (Estimate): January 22, 2009

Study Record Updates

• Last Update Posted (Estimate): June 15, 2012
• Last Update Submitted That Met QC Criteria: June 8, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: CCR5-tropic HIV-1 virus
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Tenofovir; Emtricitabine; Ritonavir; Lopinavir; Maraviroc; Darunavir; Atazanavir Sulfate
• Other Study ID Numbers: A4001078