HIV-1Phase 3MODERNNCT01345630
Comparative Trial Of Maraviroc Versus Emtricitabine/Tenofovir Both With Darunavir/Ritonavir In Antiretroviral-Naive Patients Infected With CCR5 Tropic HIV 1
A Phase 3 study testing Maraviroc, Emtricitabine/tenofovir and darunavir/ritonavir 800/100 mg in people with HIV-1, run by ViiV Healthcare at 177 sites in 19 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1
- What is being tested?
- Maraviroc, Emtricitabine/tenofovir and darunavir/ritonavir 800/100 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 813 participants
- Where
- 177 sitesin 19 countries
- Study dates
- Sep 2011to Jan 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
177 sites in 19 countries.
177 sites in 19 countries
United States84 sites
AIDS Research Consortium of Atlanta
Atlanta, Georgia, 30312
University of Colorado Denver - University of Colorado Hospital
Aurora, Colorado, 80045
Central Texas Clinical Research
Austin, Texas, 78705
Be Well Medical Center, PC
Berkley, Michigan, 48072
University of Alabama at Birmingham - 1917 Research Clinic
Birmingham, Alabama, 35294
Erie County Medical Center
Buffalo, New York, 14215
I.D. Consultants, P.A.
Charlotte, North Carolina, 28209
Northwestern University/NMH
Chicago, Illinois, 60611
Northwestern University
Chicago, Illinois, 60611
Howard Brown Health Center
Chicago, Illinois, 60613
University of Cincinnati - Department of Internal Medicine
Cincinnati, Ohio, 45267
Dallas Diabetes and Endocrine Center
Dallas, Texas, 75230
Parkland Memorial Hospital
Dallas, Texas, 75235
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
North Texas Infectious Diseases Consultants, PA
Dallas, Texas, 75246
DeKalb Medical Diagnostic Breast Center
Decatur, Georgia, 30033
Infectious Disease Specialists of Atlanta
Decatur, Georgia, 30033
Kaiser Permanente of Colorado
Denver, Colorado, 80205
University Physicians Group
Detroit, Michigan, 48201
Wayne State University
Detroit, Michigan, 48201
Henry Ford Health System
Detroit, Michigan, 48202
Michigan State University College of Osteopathic Medicine - Department of Internal Medicine
East Lansing, Michigan, 48824
Biomedical and Health Institutional Review Board
East Lansing, Michigan, 48825
Broward Health - Comprehensive Care Center
Fort Lauderdale, Florida, 33311
Broward General Medical Center
Fort Lauderdale, Florida, 33316
(DEXA Scan Facility) East Carolina University Brody Outpatient Center
Greenville, North Carolina, 27834
East Carolina University Division of Infectious Diseases
Greenville, North Carolina, 27834
Kaiser Permanente
Hayward, California, 94545
Health Services Center
Hobson City, Alabama, 36201
Therapeutic Concepts, PA
Houston, Texas, 77004
Research Access Network
Houston, Texas, 77098
The Office of Dr. Gordon E. Crofoot, M.D., PA
Houston, Texas, 77098
University of Iowa, University of Hospitals and Clinics - Division of Infectious Disease
Iowa City, Iowa, 52242
Kansas City Free Health Clinic
Kansas City, Missouri, 64111
Ingham County Health Department
Lansing, Michigan, 48911
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Dr. Anthony Mills, MD, Inc.
Los Angeles, California, 90069
The Kinder Medical Group
Miami, Florida, 33133
UMHC/Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
University of Miami AIDS Clinical Research Unit
Miami, Florida, 33136
University of Miami
Miami, Florida, 33136
Community AIDS Resource Inc dba Care Resource
Miami, Florida, 33137
Miami Research Associates
Miami, Florida, 33143
Wohlfeiler, Piperato and Associates, LLC
Miami Beach, Florida, 33139
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Jersey Shore University Medical Center
Neptune City, New Jersey, 07753
Brandywine Common
Neptune City, New Jersey, 07754
Jersey Shore University Medical Center
Neptune City, New Jersey, 07754
Yale - New Haven Hospital Nathan Smith Clinic
New Haven, Connecticut, 06504
Yale University
New Haven, Connecticut, 06510
Tulane University School of Medicine
New Orleans, Louisiana, 70112
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
Beth Israel Medical Center - AIDS Clinical Trials Unit
New York, New York, 10003
AIDS Community Research Initiative of America (ACRIA)
New York, New York, 10018
Research Across America
New York, New York, 10022
Dr. Howard A. Grossman, M.D.
New York, New York, 10107
Saint Michael's Medical Center
Newark, New Jersey, 07102
Orange Coast Medical Group
Newport Beach, California, 92663
Circle CARE Center
Norwalk, Connecticut, 06851
University of Nebraska Medical Center
Omaha, Nebraska, 68106
Desert Oasis Healthcare Medical Group
Palm Springs, California, 92262
Infectious Diseases Associates of Northwest Florida, PA
Pensacola, Florida, 32504
AIDS Care
Rochester, New York, 14607
University of California Davis Research
Sacramento, California, 95814
TICON I Research Clinic (DEXA Scan only)
Sacramento, California, 95817
Kaiser Hospital Sacramento
Sacramento, California, 95825
Synarc Inc.
San Francisco, California, 94105
Investigational Drugs Pharmacy
San Francisco, California, 94118
Kaiser Permanente - Clinical Trials Unit
San Francisco, California, 94118
Kaiser Permanente Santa Clara
Santa Clara, California, 95051
Swedish Medical Center
Seattle, Washington, 98104
Swedish Medical Center
Seattle, Washington, 98122
Baystate Infectious Diseases Clinical Research
Springfield, Massachusetts, 01199
St. Joseph's Hospital Diagnostic Center
Tampa, Florida, 33067
University of South Florida Health-HIV Clinical Research Unit
Tampa, Florida, 33602
Infectious Disease Research Institute, Inc.
Tampa, Florida, 33614
Osteoporosis Care Center
Tampa, Florida, 33614
Quest Diagnostic Laboratory
Tampa, Florida, 33614
The University of Toledo Medical Center
Toledo, Ohio, 43614
Kaiser Permanente
Union City, California, 94587
New York Medical College
Valhalla, New York, 10595
Capital Medical Associates, PC
Washington D.C., District of Columbia, 20036
George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, 20037
Rowan Tree Medical, PA
Wilton Manors, Florida, 33305
France14 sites
Hopital Saint-andre
Bordeaux, France, 33075
Hopital Henri Mondor
Créteil, 94000
Hopital Bicetre
Le Kremlin-Bicêtre, 94275
Hopital de la Croix Rousse
Lyon, 69317
Hopital Gui de Chauliac
Montpellier, 34295
CHU de Nantes - Hotel Dieu
Nantes, 44035
CHR d'Orleans la Source
Orléans, Cedex 02, 45067
Hopital Saint Antoine
Paris, Cedex 12, 75571
Hopital Bichat
Paris, Cedex 18, 75877
Hôpital de la Pitié Salpétrière
Paris, 75013
Hopital Tenon, Service des Maladies Infectieuses
Paris, 75020
Hopital Saint-Louis
Paris, 75475
Nouvel Hopital Civil
Strasbourg, 67091
Centre Hospitalier de Tourcoing
Tourcoing, 59208
Germany12 sites
Praxis Christiane Cordes
Berlin, 10243
Studiengesellschaft mbH Gubener 37
Berlin, 10243
EPIMED - Gesellschaft fuer epidemiologische und klinische Forschung in der Medizin mbH
Berlin, 12157
Universitaetsklinikum Bonn, Immunologische Ambulanz HIV
Bonn, 53127
Klinikum der Universitaet zu Koeln, Klinik I fuer Innere Medizin
Cologne, 50937
Klinikum der J.W. Goethe-Universitaet, Medizinische Klinik II
Frankfurt am Main, 60590
InfektioResearch GmbH & Co. KG
Frankfurt am Main, 60596
ifi - Studien und Projekte GmbH
Hamburg, 20099
ICH - Study - Center GmbH & Co. KG
Hamburg, 20146
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, 20246
MUC Research Group GbR
München, 80335
Ludwig-Maximilians-Universitaet, Medizinische Poliklinik - Klinikum Innenstadt
München, 80336
Spain9 sites
Hospital General Universitario de Alicante
Alicante, Alicante, 03010
Hospital del Mar
Barcelona, Barcelona, 08003
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, 08025
Hospital Clinic I Provincial de Barcelona
Barcelona, Barcelona, 08036
Hospital Universitario Reina Sofia - Hospital Provincial
Córdoba, Cordoba, 14004
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital General Universitario Gregorio Marañon
Madrid, Madrid, 28007
Hospital Universitario de La Paz
Madrid, Madrid, 28046
Hospital Universitario Virgen de la Macarena
Seville, Sevilla, 41007
United Kingdom9 sites
Dept of Sexual Health & HIV Medicine
Birmingham, B9 5SS
HIV Research Department, Elton John Centre
Brighton, BN2 1ES
Regional Infectious Diseases Unit
Edinburgh, EH4 2XU
Grahame Hayton Unit, Ambrose King Centre, Royal London Hospital,
London, E1 1BB
Ian Charleson Day Centre, Royal Free Hospital
London, NW3 2QG
Queen Elizabeth Hospital
London, SE18 4QH
St Stephen's Centre, Chelsea and Westminster Hospital NHS Foundation Trust
London, SW10 9NH
Centre for Sexual Health & HIV Research, University College London
London, WC1E 6AU
Department of Infectious Diseases & Tropical Medicine, Pennine Acute Trust Hospitals
Manchester, M8 5RB
Australia7 sites
Brisbane Sexual Health and HIV Service
Brisbane, Queensland, 4000
Melbourne Sexual Health Centre
Carlton, Victoria, 3053
East Sydney Doctors
Darlinghurst, New South Wales, 2010
Holdsworth House General Practice
Darlinghurst, New South Wales, 2010
St Vincent's Hospital
Darlinghurst, New South Wales, 2010
Clinical Research Unit, Infectious Diseases
Melbourne, Victoria, 3004
Taylor Square Private Clinic
Surry Hills, New South Wales, 2010
Canada7 sites
Clinique Medicale L'Actuel
Montreal, Quebec, H2L 4P9
Clinique Medicale du Quartier Latin
Montreal, Quebec, H2L 5B1
The Ottawa Hospital-Riverside Campus
Ottawa, Ontario, K1H 7W9
The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Maple Leaf Research / Maple Leaf Medical Clinic
Toronto, Ontario, M5G 1K2
University Health Network / Toronto General Hospital
Toronto, Ontario, M5G 2N2
Vancouver ID Research and Care Centre Society
Vancouver, British Columbia, V6Z 2C7
Belgium6 sites
Instituut voor Tropische Geneeskunde
Antwerp, B-2000
C.H.U. St-Pierre
Brussels, 1000
Hôpital Universitaire Erasme
Brussels, 1070
Cliniques Universitaires St-Luc
Brussels, 1200
Universitair Ziekenhuis Gent
Ghent, B-9000
C.H.U. Sart-Tilman
Liège, 4000
Puerto Rico6 sites
Innovative Care PSC
Bayamón, PR, 00959
Ararat Research Center
Ponce, PR, 00717
Medical Center University Hospital
Rio Piedras, PR, 00935
University of Puerto Rico Medical Sciences Campus
Rio Piedras, 00935
Clinical Research Puerto Rico
San Juan, PR, 00909
HOPE Clinical Research
San Juan, PR, 00909
Portugal4 sites
Hospital Prof. Doutor Fernando Fonseca E.P.E.
Amadora, Portugal, 2720-276
Centro Hospitalar de Lisboa - Zona Central - Hospital Santo António Capuchos
Lisbon, 1169-050
Hospital Sta. Maria
Lisbon, 1649-035
Hospital São João
Porto, 4200-319
Sweden4 sites
SU Ostra sjukhuset, Infektionsmottagningen
Gothenburg, 416 85
Skanes Universitetssjukhus
Malmö, 205 02
Sodersjukhuset, Venhalsan
Stockholm, 118 83
Karolinska Universitetssjukhuset Huddinge
Stockholm, 141 86
Switzerland4 sites
Universitaetsspital Basel Infektiologie und Spitalhygiene
Basel, 4031
Inselspital Universitaetsklinik fuer Infektiologie
Bern, 3010
Kantonsspital St. Gallen
Sankt Gallen, 9007
Universitatsspital Zurich
Zurich, 8091
Denmark3 sites
Hvidovre Hospital, Infektionsmedicinsk afd.
Hvidovre, 2650
Rigshospitalet, Epidemiklinikken
Koebenhavn OE, 2100
Odense Universitetshospital
Odense, 5000
Poland3 sites
Wojewodzki Szpital Obserwacyjno - Zakazny im. Tadeusza Browicza
Bydgoszcz, 85-030
SPZOZ Wojewodzki Szpital Zakazny
Warsaw, 01-201
EMC Instytut Medyczny S.A. Przychodnia przy ul. Lowieckiej
Wroclaw, 50-220
Finland1 site
Infektiosairauksien poliklinikka,HUS Auroran sairaala, rakennus 5, 1. krs
Helsinki, 00250
Hungary1 site
Egyesitett Szent Istvan és Szent Laszlo Korhaz-Rendelointezet
Budapest, 1097
About this study
Official title: 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.
Read the 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).
- Conditions
- HIV-1
- Being tested
- Maraviroc, Emtricitabine/tenofovir, darunavir/ritonavir 800/100 mg, placebo for emtricitabine/tenofovir, placebo for maraviroc
- Keywords
- Double-blind, comparative, trial, maraviroc, versus, emtricitabine/tenofovir, both with darunavir/ritonavir, antiretroviral-naive, Ccr5 tropic, Hiv 1, patients.
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MaravirocDrug
Also called Selzentry, Celsentri
Maraviroc tablet 150 mg once daily for 96 weeks.
Emtricitabine/tenofovirDrug
Also called Truvada
Emtricitabine/tenofovir tablet 200/300 mg once daily for 96 weeks.
darunavir/ritonavir 800/100 mgDrug
darunavir/ritonavir 800/100 mg
placebo for emtricitabine/tenofovirDrug
Also called Truvada
placebo for emtricitabine/tenofovir
placebo for maravirocDrug
Also called Selzentry, Celsentri
placebo for maraviroc
| Study group | Role | What they receive |
|---|---|---|
| Maraviroc | Experimental | Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily. Receives: Drug: Maraviroc; Drug: darunavir/ritonavir 800/100 mg; Drug: placebo for maraviroc |
| Emtricitabine/tenofovir | Active comparator | Emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. Receives: Drug: Emtricitabine/tenofovir; Drug: placebo for emtricitabine/tenofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL.
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.
Measured: Week 48
Secondary outcomes (24)
Frequency of Adverse Events (AE).
Number of participants with treatment-emergent non serious AEs
Measured: Week 96
Number of Participants With Grade 3 or 4 AEs
Number of participants with grade 3 or 4 AEs are presented here.
Measured: Week 96
Number of Participants Who Discontinued Due to AEs
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.
Measured: Week 96
Number of Treatment-related AEs
Number of treatment-related AEs are presented here.
Measured: Week 96
Number of Participants With Treatment-emergent Serious Adverse Events
Total number of participants with treatment-emergent serious adverse events are reported
Measured: Week 96
Number of Participants With Abnormal Laboratory Values
Number of participants with laboratory abnormalities are reported
Measured: Week 96
Severity of Abnormal Laboratory Values
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.
Measured: 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).
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.
Measured: Week 48
Virologic Outcomes at Week 48 Using Protocol-Defined Treatment Failure (PDTF).
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).
Measured: Week 48
Tropism Change Between Screening or Baseline and PDTF
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.
Measured: Week 48
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria.
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.
Measured: 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
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.
Measured: Week 48
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 4 (CD4, Cell/mm^3)
The differences in the magnitude of changes in CD4+ at Baseline and at Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
Measured: Baseline, Week 48
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%)
The differences in the magnitude of changes in CD4+ from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
Measured: Baseline, Week 48
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 8 (CD8, Cell/mm^3)
The differences in the magnitude of changes in CD8+ cell counts from baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
Measured: Baseline, Week 48
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%)
The differences in the magnitude of changes in CD8+ cell counts from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
Measured: Baseline, Week 48
Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48
The differences in the magnitude of changes in CD4+/CD8+ ratio from Baseline through Weeks 48 for maraviroc versus emtricitabine/tenofovir were compared.
Measured: Baseline, Week 48
Changes in Peripheral Fat Distribution Using Dual Energy X-ray Absorptiometry [DEXA] Scan From Baseline and at Week 48.
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.
Measured: Week 48
Changes in Trunk to Limb Fat Distribution Using DEXA Scan From Baseline and at Week 48
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.
Measured: Week 48
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Total Hip BMD
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.
Measured: Week 48
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Femoral Neck BMD
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.
Measured: 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
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.
Measured: Week 48
Change in Bone Turnover Markers From Baseline and at Week 48 - Blood Osteocalcin
Bone turnover marker, osteocalcin, was collected in the subset of participants participating in the DEXA scan sub-study.
Measured: Week 48
Change in Bone Turnover Markers From Baseline and at Week 48 - Type 1 Collagen Peptide (CTX-1)
Bone turnover marker, C-telopeptide of type 1 collagen (CTx), was collected in the subset of participants participating in the DEXA scan sub-study.
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2011 (estimated)
- Study startSep 2011
- Primary completionAug 2013
- Study completionJan 2014
Why it stopped: See termination reason in detailed description.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV-1Studies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 813 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01345630
- Sponsor's protocol ID
- A4001095
- Other IDs
- 2010-021785-30
- Acronym
- MODERN
- Status last verified
- Dec 2015
- First submitted
- 27 Apr 2011
- Last updated
- 14 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01345630
- Acronym / sponsor ID
- MODERN / A4001095
- Conditions
- HIV-1
- Keywords
- Double-blind, comparative, trial, maraviroc, versus, emtricitabine/tenofovir, both with darunavir/ritonavir, antiretroviral-naive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 813 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Study start
- Sep 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 2 May 2011 (estimated)
- Results
- Posted 14 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Maraviroc | Experimental | Drug: Maraviroc, Drug: darunavir/ritonavir 800/100 mg, Drug: placebo for maravirocMaraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily. |
| Emtricitabine/tenofovir | Active comparator | Drug: Emtricitabine/tenofovir, Drug: placebo for emtricitabine/tenofovirEmtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MaravirocAlso: Selzentry, CelsentriMaraviroc tablet 150 mg once daily for 96 weeks. | Drug | Maraviroc |
| Emtricitabine/tenofovirAlso: TruvadaEmtricitabine/tenofovir tablet 200/300 mg once daily for 96 weeks. | Drug | Emtricitabine/tenofovir |
| darunavir/ritonavir 800/100 mgdarunavir/ritonavir 800/100 mg | Drug | Maraviroc |
| placebo for emtricitabine/tenofovirAlso: Truvadaplacebo for emtricitabine/tenofovir | Drug | Emtricitabine/tenofovir |
| placebo for maravirocAlso: Selzentry, Celsentriplacebo for maraviroc | Drug | Maraviroc |
Primary outcome
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.
24 secondary outcomes
Frequency of Adverse Events (AE).
Time frame: Week 96
Number of Participants With Grade 3 or 4 AEs
Time frame: Week 96
Number of Participants Who Discontinued Due to AEs
Time frame: Week 96
Number of Treatment-related AEs
Time frame: Week 96
Number of Participants With Treatment-emergent Serious Adverse Events
Time frame: Week 96
Number of Participants With Abnormal Laboratory Values
Time frame: Week 96
Severity of Abnormal Laboratory Values
Time frame: 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).
Time frame: Week 48
Virologic Outcomes at Week 48 Using Protocol-Defined Treatment Failure (PDTF).
Time frame: Week 48
Tropism Change Between Screening or Baseline and PDTF
Time frame: Week 48
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria.
Time frame: 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
Time frame: Week 48
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
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%)
Time frame: Baseline, Week 48
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
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%)
Time frame: Baseline, Week 48
Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48
Time frame: Baseline, Week 48
Changes in Peripheral Fat Distribution Using Dual Energy X-ray Absorptiometry [DEXA] Scan From Baseline and at Week 48.
Time frame: Week 48
Changes in Trunk to Limb Fat Distribution Using DEXA Scan From Baseline and at Week 48
Time frame: Week 48
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Total Hip BMD
Time frame: Week 48
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Femoral Neck BMD
Time frame: 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
Time frame: Week 48
Change in Bone Turnover Markers From Baseline and at Week 48 - Blood Osteocalcin
Time frame: Week 48
Change in Bone Turnover Markers From Baseline and at Week 48 - Type 1 Collagen Peptide (CTX-1)
Time frame: Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
177 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Maraviroc, Emtricitabine/tenofovir and darunavir/ritonavir 800/100 mg in people with HIV-1, run by ViiV Healthcare at 177 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 177 sites in United States, France, Germany, Spain, United Kingdom and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL. (time frame: Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2016.