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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Human Immunodeficiency Virus-1

Intervention / Treatment
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* Drug: maraviroc
* Drug: maraviroc


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>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<br>* 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))<br>* Other names: maraviroc =Celsentri, Selzentry; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia; darunavir=Prezista;|
| Experimental: Arm B<br>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<br>* 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))<br>* Other names: maraviroc=Celsentri, Selzentry; emtricitabine/tenofovir=Truvada; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CCR5-tropic HIV-1 virus