A Multicenter, Randomized, Double-Blind, Comparative Trial Of Maraviroc + Darunavir/Ritonavir Versus Emtricitabine/Tenofovir + Darunavir/Ritonavir For The Treatment Of Antiretroviral-Naive Hiv-Infected Patients With Ccr5-Tropic Hiv-1
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- ViiV Healthcare
- Enrollment
- 813
- Locations
- 174
- Primary Endpoint
- Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL.
Study Overview
Brief Summary
The purpose of this study is to assess whether maraviroc administered once daily is non-inferior to emtricitabine/tenofovir also administered once daily each in combination with darunavir/ritonavir in the treatment of antiretroviral-naive patients as evaluated at Week 48 of treatment.
Detailed Description
The study was terminated on October 8, 2013 following a preliminary review of the Week 48 primary efficacy data by the study's external independent Data Monitoring Committee (DMC). The DMC assessed the data as demonstrating significant differences between the treatment arms in virologic responses and failures. The DMC recommended and the Sponsor concurred that the study be terminated because of the inferior efficacy of the Maraviroc arm as compared to the comparator arm (Emtricitabine/Tenofovir).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Plasma HIV-1 RNA equal to or greater than 1,000 copies/mL measured at the Screening Visit.
- •CD4 count equal to or greater than 100 cells/mm3 at Screening.
- •Have only R5 HIV 1 at Screening as verified by a randomized tropism assay.
Exclusion Criteria
- •Prior treatment with any other HIV antiretroviral therapy for more than 14 days at any time.
- •Any evidence of genotypic/phenotypic resistance to darunavir, tenofovir, and emtricitabine.
- •CXCR4 using virus detected using randomized tropism determination or repeated failure to obtain an interpretable tropism result.
Arms & Interventions
Maraviroc
Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.
Intervention: Maraviroc (Drug)
Maraviroc
Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.
Intervention: darunavir/ritonavir 800/100 mg (Drug)
Maraviroc
Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.
Intervention: placebo for maraviroc (Drug)
Emtricitabine/tenofovir
Emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.
Intervention: Emtricitabine/tenofovir (Drug)
Emtricitabine/tenofovir
Emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.
Intervention: placebo for emtricitabine/tenofovir (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL.
Time Frame: Week 48
The proportion of participants who achieved HIV-1 RNA \<50 copies/mL at week 48 was assessed according to Food and Drug Administration's (FDA's) Missing, Switch, Discontinuation'=Failure (MSDF) Snapshot algorithm. The algorithm used the plasma HIV-1 RNA in the Week 48 visit window, followed the "virology-first principle" and considers a participant who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure.
Secondary Outcomes
- Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48(Baseline, Week 48)
- Frequency of Adverse Events (AE).(Week 96)
- Number of Participants With Grade 3 or 4 AEs(Week 96)
- The Relationship Between the Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL at the Week 48 and the Screening Tropism Test (Genotype Test or ESTA).(Week 48)
- Number of Participants With Abnormal Laboratory Values(Week 96)
- Virologic Outcomes at Week 48 Using Protocol-Defined Treatment Failure (PDTF).(Week 48)
- Number of Treatment-related AEs(Week 96)
- Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria.(Week 48)
- Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria(Week 48)
- Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%)(Baseline, Week 48)
- Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 8 (CD8, Cell/mm^3)(Baseline, Week 48)
- Number of Participants Who Discontinued Due to AEs(Week 96)
- Severity of Abnormal Laboratory Values(Week 96)
- Changes in Peripheral Fat Distribution Using Dual Energy X-ray Absorptiometry [DEXA] Scan From Baseline and at Week 48.(Week 48)
- Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Femoral Neck BMD(Week 48)
- Number of Participants With Treatment-emergent Serious Adverse Events(Week 96)
- Tropism Change Between Screening or Baseline and PDTF(Week 48)
- Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 4 (CD4, Cell/mm^3)(Baseline, Week 48)
- Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Total Hip BMD(Week 48)
- Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%)(Baseline, Week 48)
- Changes in Trunk to Limb Fat Distribution Using DEXA Scan From Baseline and at Week 48(Week 48)
- Change in Bone Turnover Markers From Baseline and at Week 48 - Type 1 Collagen Peptide (CTX-1)(Week 48)
- Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - AP Lumbar Spine (L1 - L4) BMD(Week 48)
- Change in Bone Turnover Markers From Baseline and at Week 48 - Blood Osteocalcin(Week 48)