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Comparative Trial Of Maraviroc Versus Emtricitabine/Tenofovir Both With Darunavir/Ritonavir In Antiretroviral-Naive Patients Infected With CCR5 Tropic HIV 1 (MODERN)

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01345630
First received: April 27, 2011
Last updated: December 11, 2015
Last verified: December 2015

April 27, 2011
December 11, 2015
September 2011
August 2013   (final data collection date for primary outcome measure)
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
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.
The proportion of patients with plasma HIV 1 RNA <50 copies/mL at Week 48. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01345630 on ClinicalTrials.gov Archive Site
  • Frequency of Adverse Events (AE). [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
    Number of participants with treatment-emergent non serious AEs
  • Number of Participants With Grade 3 or 4 AEs [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
    Number of participants with grade 3 or 4 AEs are presented here.
  • Number of Participants Who Discontinued Due to AEs [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
    Number of participants who discontinued due to AEs are reported here. Three participants (two from the MVC+DRV/r arm and one from the FTC/TDF+DRV/r arm) were not considered as discontinued due to AE because other reasons for discontinuation were prioritized for these participants.
  • Number of Treatment-related AEs [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
    Number of treatment-related AEs are presented here.
  • Number of Participants With Treatment-emergent Serious Adverse Events [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
    Total number of participants with treatment-emergent serious adverse events are reported
  • Number of Participants With Abnormal Laboratory Values [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
    Number of participants with laboratory abnormalities are reported
  • Severity of Abnormal Laboratory Values [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
    Number of participants who had clinically significant laboratory abnormalities of Grade 3 and Grade 4 according to DAIDS. Abnormality incidence of highest grade was reported for a labcode for each individual participant.
  • 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). [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The relationship of the proportion of participants achieving HIV-1 RNA <50 copies/mL at Week 48 with the screening tropism test for the MVC containing regimen was analyzed. Virologic response for a participant at Week 48 was derived using the FDA's Snapshot MSDF algorithm. Difference in proportions of patients with plasma HIV-1 RNA <50 copies/mL at week 48 between the maraviroc and the emtricitabine/tenofovir treatment arms, with two-sided 95% confidence interval, among patients who are R5 by genotype (including some who were originally randomized to ESTA and are R5 by genotype upon retesting), were calculated via the Maximum Likelihood method. The estimate was adjusted for the screening plasma HIV RNA level (<100,000 vs. ≥100,000) copies/mL via the Mantel Haenszel (MH) method.
  • Virologic Outcomes at Week 48 Using Protocol-Defined Treatment Failure (PDTF). [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Per the protocol participants who meet the following criteria were regarded as PDTFs requiring a confirmatory plasma HIV-1 RNA determination: • Decrease in plasma HIV-1 RNA <1 log10 from baseline after Week 4 unless plasma HIV-1 RNA is <50 copies/mL, or • Plasma HIV-1 RNA >1.0 log10 above the nadir value after Week 4 where the nadir is the lowest plasma HIV-1 RNA concentration, or • Plasma HIV-1 RNA ≥50 copies/mL at any time after Week 24, or • Plasma HIV-1 RNA ≥50 copies/mL after suppression to <50 copies/mL on two consecutive visits, or • Decrease in plasma HIV-1 RNA ≤2 log10 from baseline on or after Week 12 unless plasma HIV-1 RNA is <400 copies/mL. Decrease in plasma HIV-1 RNA ≤2 log10 from baseline on or after Week 12 unless plasma HIV-1 RNA is <50 copies/mL (before August 30 2012) or <400 copies/mL (after August 30 2012).
  • Tropism Change Between Screening or Baseline and PDTF [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    For participants meeting the PDTF criteria, tropism was assessed using the original randomized and alternate assays (ie, both genotype testing and ESTA). Data reported here corresponds to the timepoint at or after PDTF.
  • Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    For participants meeting the PDTF criteria, viral resistance to maraviroc for maraviroc treated participants was assessed in patients with R5 virus at failure. The resistance level is calculated by reference to a laboratory strain of virus that is analyzed in parallel with the clinical isolate to identify 50% inhibitory concentrations (IC50). The maximal percent inhibition is the percent inhibition that is achieved in a titration of the drug at high concentrations when the addition of more drug does not result in increased inhibition. Maximal percent inhibition is obtained in the same way as the titration for IC50, but the key measure is of the plateau height of percent inhibition, where increased concentration of maraviroc does not result in additional inhibition. This is consistent with the virus developing some ability to use maraviroc-bound CCR5 for entry. A significant change in IC50 is not required for this mechanism.
  • 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 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    For participants meeting the PDTF criteria, viral resistance (both genotypic and phenotypic) to NRTI, NNRTI, and PI's were assessed at Baseline and on-treatment. The assessment was performed using the overall (i.e. net) susceptibility score provided using the PhenoSense GT assay. The number of participants with successful assessments were 15/17 for the MVC+DRV/r arm and 3/3 for the FTC/TDF+DRV/r arm.
  • Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 4 (CD4, Cell/mm^3) [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    The differences in the magnitude of changes in CD4+ at Baseline and at Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
  • Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%) [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    The differences in the magnitude of changes in CD4+ from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
  • Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 8 (CD8, Cell/mm^3) [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    The differences in the magnitude of changes in CD8+ cell counts from baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
  • Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%) [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    The differences in the magnitude of changes in CD8+ cell counts from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
  • Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    The differences in the magnitude of changes in CD4+/CD8+ ratio from Baseline through Weeks 48 for maraviroc versus emtricitabine/tenofovir were compared.
  • Changes in Peripheral Fat Distribution Using Dual Energy X-ray Absorptiometry [DEXA] Scan From Baseline and at Week 48. [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    A sub-study was conducted in which the participants underwent whole-body DEXA scans to evaluate peripheral fat tissue estimates for left and right arms and legs and truncal fat mass and truncal lean mass. Truncal abdominal fat were estimated from the DEXA scan field set on the torso. The effects on estimates of fat mass and lean mass were addressed by providing LSMs of change from baseline.
  • Changes in Trunk to Limb Fat Distribution Using DEXA Scan From Baseline and at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    A sub-study was conducted in which the participants underwent whole-body DEXA scans to evaluate peripheral fat tissue estimates for left and right arms and legs and truncal fat mass and truncal lean mass. Truncal abdominal fat were estimated from the DEXA scan field set on the torso. The effects on estimates of fat mass and lean mass were addressed by providing LSMs of change from baseline.
  • Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Total Hip BMD [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from baseline bone mineral density of the lumbar spine (L1-L4), left total hip and femoral neck as measured by the DEXA scan.
  • Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Femoral Neck BMD [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from Baseline bone mineral density femoral neck as measured by the DEXA scan.
  • Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - AP Lumbar Spine (L1 - L4) BMD [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from baseline bone mineral density of the lumbar spine (L1-L4) as measured by the DEXA scan.
  • Change in Bone Turnover Markers From Baseline and at Week 48 - Blood Osteocalcin [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Bone turnover marker, osteocalcin, was collected in the subset of participants participating in the DEXA scan sub-study.
  • Change in Bone Turnover Markers From Baseline and at Week 48 - Type 1 Collagen Peptide (CTX-1) [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    Bone turnover marker, C-telopeptide of type 1 collagen (CTx), was collected in the subset of participants participating in the DEXA scan sub-study.
  • Safety: Frequency, severity and relationship of adverse events to test drug; serious adverse events; discontinuations due to adverse events; and frequency and severity of abnormal laboratory values. [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
  • The relationship between the proportion of patients with plasma HIV 1 RNA <50 copies/mL at the Week 48 and Week 96 visits and the screening tropism test (Genotype test or Enhanced Sensitivity Trofile Assay [ESTA]). [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
  • Virologic Response: Proportion of patients with plasma HIV RNA <50 copies/mL at Week 96. [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
  • Immunological Response [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    1. Changes in CD4+ T lymphocyte (CD4) cell counts and percent change from Baseline;
    2. Changes in CD8+ T lymphocyte (CD8) cell counts and percent change from Baseline;
    3. Changes in CD4+/CD8+ ratio and changes from Baseline.
  • Evolution of viral resistance and tropism change between Screening or Baseline and the time of confirmation of virologic failure or the last on treatment time point: [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    1. HIV 1 tropism (Genotype test)
    2. For virologic failure with R5 virus, viral resistance to maraviroc (maraviroc treated patients only).
    3. Viral resistance (Genotype and Phenotype) to nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) and non nucleoside reverse transcriptase inhibitors (NNRTI) [reverse transcriptase inhibitors, RTI] and protease inhibitors (PI).
  • Changes in peripheral fat distribution and trunk to limb fat ratio (using Dual Energy X-ray Absorptiometry [DEXA] scan) from Baseline and at Weeks 48 and 96 (107 patients per treatment arm). [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
  • Changes in bone mineral density (using DEXA scan and serum markers) from Baseline and at Weeks 48 and 96 (107 patients per treatment arm). [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Comparative Trial Of Maraviroc Versus Emtricitabine/Tenofovir Both With Darunavir/Ritonavir In Antiretroviral-Naive Patients Infected With CCR5 Tropic HIV 1
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
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.
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).
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
HIV-1
  • Drug: Maraviroc
    Maraviroc tablet 150 mg once daily for 96 weeks.
    Other Name: Selzentry, Celsentri
  • Drug: Emtricitabine/tenofovir
    Emtricitabine/tenofovir tablet 200/300 mg once daily for 96 weeks.
    Other Name: Truvada
  • Drug: darunavir/ritonavir 800/100 mg
    darunavir/ritonavir 800/100 mg
  • Drug: placebo for emtricitabine/tenofovir
    placebo for emtricitabine/tenofovir
    Other Name: Truvada
  • Drug: placebo for maraviroc
    placebo for maraviroc
    Other Name: Selzentry, Celsentri
  • Experimental: Maraviroc
    Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.
    Interventions:
    • Drug: Maraviroc
    • Drug: darunavir/ritonavir 800/100 mg
    • Drug: placebo for maraviroc
  • Active Comparator: Emtricitabine/tenofovir
    Emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.
    Interventions:
    • Drug: Emtricitabine/tenofovir
    • Drug: placebo for emtricitabine/tenofovir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
813
January 2014
August 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Austria,   Belgium,   Canada,   Denmark,   Finland,   France,   Germany,   Hungary,   Italy,   Netherlands,   Poland,   Portugal,   Puerto Rico,   Spain,   Sweden,   Switzerland,   United Kingdom
Mexico
 
NCT01345630
A4001095, 2010-021785-30
Yes
Not Provided
Not Provided
ViiV Healthcare
ViiV Healthcare
Pfizer
Study Director: Pfizer CT.gov Call Center Pfizer
ViiV Healthcare
December 2015

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