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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00827112
First received: January 21, 2009
Last updated: June 8, 2012
Last verified: June 2012

January 21, 2009
June 8, 2012
March 2009
July 2010   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
The percentage of patients with plasma HIV-1 RNA <50 copies/mL in each treatment arm at 48 weeks [ Time Frame: week 48 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00827112 on ClinicalTrials.gov Archive Site
  • HIV-1 RNA Levels at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 [ Time Frame: Baseline , Days 4, 7, 10 and 14 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Average Observed Plasma Concentration (Cavg) of Maraviroc [ Time Frame: Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 16, Week 24, Week 48, Week 96 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Time to Loss of Virological Response (TLOVR) [ Time Frame: Baseline through Week 96 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 16, Week 24, Week 48, Week 96 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 16, Week 24, Week 48, Week 96 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of Participants With Genotypic Resistance [ Time Frame: Week 96 or Time of treatment failure ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 96 or Time of treatment failure ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 96 or Time of treatment Failure ] [ Designated as safety issue: No ]
    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.
  • Safety and tolerability of the treatment with novel combinations of maraviroc (Selzentry, Celsentri with atazanavir/ritonavir; and another combination regimen (atazanavir and emtricitabine/tenofovir) in treatment-naïve HIV-1 infected subjects [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
  • Plasma HIV RNA of the first 15 patients enrolled in two treatment arms at Days 4, 7, 10, and 14 (in US sites only) [ Time Frame: Days 4, 7, 10, and 14 ] [ Designated as safety issue: No ]
  • PK of maraviroc of the patients enrolled in maraviroc arm [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Virological Response [ Time Frame: wk 16,24,48 ] [ Designated as safety issue: No ]
  • Immunological Response [ Time Frame: wk 16,24,48 ] [ Designated as safety issue: No ]
  • Evolution of viral resistance and tropism [ Time Frame: at the time of treatment failure ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Human Immunodeficiency Virus-1
  • 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 Name: 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 Name: maraviroc=Celsentri, Selzentry; emtricitabine/tenofovir=Truvada; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia
  • 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.
    Intervention: Drug: maraviroc
  • 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.

    Intervention: Drug: maraviroc
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
129
July 2011
July 2010   (final data collection date for primary outcome measure)

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.
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Spain,   Germany
 
NCT00827112
A4001078
Yes
ViiV Healthcare
ViiV Healthcare
Pfizer
Study Director: Pfizer CT.gov Call Center Pfizer
ViiV Healthcare
June 2012

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