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
Results First Received: August 14, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: HIV-1
Interventions: Drug: Maraviroc
Drug: Emtricitabine/tenofovir
Drug: darunavir/ritonavir 800/100 mg
Drug: placebo for emtricitabine/tenofovir
Drug: placebo for maraviroc

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Overall, 1423 participants were screened and 813 participants randomized in the study. A total of 797 participants were treated (396 were treated in the maraviroc + darunavir/ritonavir [MVC+DRV/r] group and 401 in the emtricitabine/tenofovir + darunavir/ritonavir [FTC/TDF+DRV/r] group). The study was conducted in 138 sites in 18 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized to undergo either genotype testing or enhanced Trofile assay (ESTA) in a 1:1 ratio. Among participants who were identified as being infected with R5 tropic HIV-1 by either testing methods, 813 were randomized in a 1:1 ratio to receive 96-week treatment either in the MVC+DRV/r arm or in the FTC/TDF+DRV/r arm.

Reporting Groups
  Description
MVC+DRV/r Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.
FTC/TDF+DRV/r Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.

Participant Flow:   Overall Study
    MVC+DRV/r     FTC/TDF+DRV/r  
STARTED     396     401  
COMPLETED     35     42  
NOT COMPLETED     361     359  
Adverse Event                 22                 23  
Lost to Follow-up                 17                 16  
Protocol Violation                 4                 1  
Medication error without associated AE                 0                 1  
Study terminated by sponsor                 254                 285  
Other reasons                 6                 8  
Withdrawn due to pregnancy                 1                 2  
No longer willing to participate                 9                 12  
Insufficient clinical response                 48                 11  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
MVC+DRV/r Participants infected with R5 HIV-1 received oral tablets of Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.
FTC/TDF+DRV/r Participants infected with R5 HIV-1 received oral tablets of emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.
Total Total of all reporting groups

Baseline Measures
    MVC+DRV/r     FTC/TDF+DRV/r     Total  
Number of Participants  
[units: participants]
  396     401     797  
Age  
[units: Years]
Mean (Standard Deviation)
  37.9  (10.9)     36.2  (10.9)     37.1  (10.9)  
Gender  
[units: Number¬†of¬†participants]
     
Female     36     34     70  
Male     360     367     727  



  Outcome Measures
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1.  Primary:   Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL.   [ Time Frame: Week 48 ]

2.  Secondary:   Frequency of Adverse Events (AE).   [ Time Frame: Week 96 ]

3.  Secondary:   Number of Participants With Grade 3 or 4 AEs   [ Time Frame: Week 96 ]

4.  Secondary:   Number of Participants Who Discontinued Due to AEs   [ Time Frame: Week 96 ]

5.  Secondary:   Number of Treatment-related AEs   [ Time Frame: Week 96 ]

6.  Secondary:   Number of Participants With Treatment-emergent Serious Adverse Events   [ Time Frame: Week 96 ]

7.  Secondary:   Number of Participants With Abnormal Laboratory Values   [ Time Frame: Week 96 ]

8.  Secondary:   Severity of Abnormal Laboratory Values   [ Time Frame: Week 96 ]

9.  Secondary:   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 ]

10.  Secondary:   Virologic Outcomes at Week 48 Using Protocol-Defined Treatment Failure (PDTF).   [ Time Frame: Week 48 ]

11.  Secondary:   Tropism Change Between Screening or Baseline and PDTF   [ Time Frame: Week 48 ]

12.  Secondary:   Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria.   [ Time Frame: Week 48 ]

13.  Secondary:   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 ]

14.  Secondary:   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 ]

15.  Secondary:   Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%)   [ Time Frame: Baseline, Week 48 ]

16.  Secondary:   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 ]

17.  Secondary:   Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%)   [ Time Frame: Baseline, Week 48 ]

18.  Secondary:   Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48   [ Time Frame: Baseline, Week 48 ]

19.  Secondary:   Changes in Peripheral Fat Distribution Using Dual Energy X-ray Absorptiometry [DEXA] Scan From Baseline and at Week 48.   [ Time Frame: Week 48 ]

20.  Secondary:   Changes in Trunk to Limb Fat Distribution Using DEXA Scan From Baseline and at Week 48   [ Time Frame: Week 48 ]

21.  Secondary:   Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Total Hip BMD   [ Time Frame: Week 48 ]

22.  Secondary:   Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Femoral Neck BMD   [ Time Frame: Week 48 ]

23.  Secondary:   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 ]

24.  Secondary:   Change in Bone Turnover Markers From Baseline and at Week 48 - Blood Osteocalcin   [ Time Frame: Week 48 ]

25.  Secondary:   Change in Bone Turnover Markers From Baseline and at Week 48 - Type 1 Collagen Peptide (CTX-1)   [ Time Frame: Week 48 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was terminated following a preliminary review of the 48- week primary clinical efficacy data by the study’s external independent Data Monitoring Committee’s recommendation based on inferior efficacy of the investigational MVC+DRV/r arm.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


No publications provided


Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01345630     History of Changes
Other Study ID Numbers: A4001095
2010-021785-30 ( EudraCT Number )
Study First Received: April 27, 2011
Results First Received: August 14, 2014
Last Updated: December 11, 2015
Health Authority: United States: Food and Drug Administration