Efficacy, Safety, and Tolerability of Cenicriviroc (CVC) in Combination With Truvada or Sustiva Plus Truvada in HIV 1-infected, Antiretroviral Treatment-naïve, Adult Patients Infected With Only CCR5-tropic Virus
A Phase 2b Randomized, Double-Blind, Double-Dummy Trial of 100 or 200 mg Once-Daily Doses of Cenicriviroc (CVC, TBR 652) or Once-Daily EFV, Each With Open-Label FTC/TDF, in HIV 1-Infected, Antiretroviral Treatment-Naïve, Adult Patients With Only CCR5-Tropic Virus
1 other identifier
interventional
143
2 countries
48
Brief Summary
This is a randomized, double-blind, double-dummy, 48-week, comparative study. Approximately 150 HIV-infected, treatment-naïve patients with CCR5-tropic virus will be stratified by HIV-1 RNA: ≥100,000 copies/mL versus \<100,000 copies/mL and will be randomized 2:2:1 to receive:
- Arm A: CVC 100 mg (2 tablets, 50 mg each) QD + CVC matching placebo (2 tablets) QD + EFV matching placebo (1 tablet) QHS + FTC/TDF (1 tablet) QD.
- Arm B: CVC 200 mg (4 tablets, 50 mg each) QD + EFV matching placebo (1 tablet) QHS + FTC/TDF (1 tablet) QD.
- Arm C: CVC matching placebo (4 tablets) QD + EFV 600 mg (1 tablet) QHS + FTC/TDF (1 tablet) QD. Doses of both CVC/placebo and EFV/ placebo will be administered as double-blinded study drug. FTC/TDF will be administered as open-label study drug in a fixed-dose combination formulation (Truvada). CVC/placebo should be taken following breakfast; EFV should be taken on an empty stomach at bedtime. HIV-1 RNA levels and CD4+ and CD8+ cell counts, percentages, and ratios will be measured at every visit. Samples for viral tropism and resistance testing in case of virologic failure will be collected at Screening and each on-treatment visit. Biomarkers associated with inflammation and immune activation will be measured at Baseline (predose) and each study visit thereafter, with flow cytometry obtained at weeks 4, 12, 24, 48, and 52. Fasting metabolic indicators of glucose control (glucose and insulin for HOMA-IR, HbA1c) and fasting lipid profiles (HDL, LDL, total cholesterol, and triglycerides) will be measured at Baseline (predose) and Weeks 4, 12, 24, 48, and 52. Waist-to-hip ratios will be measured at Baseline and Weeks 24 and 48. Plasma samples will be collected and stored for possible future studies at Baseline (predose) and every visit thereafter.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2011
48 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 18, 2011
CompletedFirst Posted
Study publicly available on registry
April 20, 2011
CompletedStudy Start
First participant enrolled
June 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2013
CompletedJuly 10, 2013
July 1, 2013
1.5 years
April 18, 2011
July 3, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24
24 weeks
Study Arms (3)
CVC 100 mg + Truvada
EXPERIMENTALCVC 200 mg + Truvada
EXPERIMENTALSustiva + Truvada
ACTIVE COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- Adult male and female, HIV-1-infected patients 18 years old and older.
- Body mass index (BMI) 18 to \< 35 kg/m2.
- Antiretroviral treatment-naïve. Treatment-naïve is defined as:
- No prior nonnucleoside reverse transcriptase inhibitor, other than in women who received a single dose of perinatal nevirapine who have no K103 viral mutation.
- No prior CCR5 antagonist therapy.
- No more than 10 days of any other prior antiretroviral therapy.
- HIV-1 CCR5-tropic-only virus.
- Plasma HIV-1 RNA level \>/=1,000 copies/mL at first Screening.
- CD4 cell count \>/=250 cells/mm3 at first Screening.
You may not qualify if:
- Presence of CXCR4- or dual/mixed-tropic HIV-1 virus.
- Presence of primary resistance mutations or phenotypic resistance to TDF, FTC, or EFV and/or mutations associated with multidrug nucleoside/nucleotide resistance.
- An active CDC category C disease (except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial).
- Any historical CD4 count \< 200 cells/mm3.
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value Grade \> 2 or total bilirubin greater than the upper limit of normal (ULN).
- History of HIV-2, hepatitis B and/or C, cirrhosis of the liver, or any known active or chronic liver disease. Hepatitis B vaccinated patients are eligible.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (48)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Southwest Center for HIV / AIDS
Phoenix, Arizona, 85006, United States
AIDS Healthcare Foundation Research Center
Beverly Hills, California, 90211, United States
Pacific Oaks Medical Group
Beverly Hills, California, 90211, United States
Providence Clinical Research
Burbank, California, 91505, United States
AIDS Research Alliance
Los Angeles, California, 90015, United States
Peter J Ruane MD Incorporated
Los Angeles, California, 90036, United States
Oasis Clinic
Los Angeles, California, 90059, United States
Anthony Mills
Los Angeles, California, 90069, United States
Orange Coast Medical Group
Newport Beach, California, 92663, United States
Stanford University ACTU
Palo Alto, California, 94304, United States
University of California at San Francisco
San Francisco, California, 94110, United States
Quest Clinical Research
San Francisco, California, 94115, United States
Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Whitman-Walker Clinic
Washington D.C., District of Columbia, 20009, United States
Therafirst Medical Center
Fort Lauderdale, Florida, 33308, United States
Gary Richmond
Fort Lauderdale, Florida, 33316, United States
Midway Immunology and Research Center
Ft. Pierce, Florida, 34982, United States
University of Miami School of Medicine
Miami, Florida, 33136, United States
Care Resource Inc.
Miami, Florida, 33137, United States
Kinder Medical Group
Miami, Florida, 33137, United States
Wohlfeiler, Piperato & Associates, LLC
Miami Beach, Florida, 33139, United States
Orlando Immunology Center
Orlando, Florida, 32803, United States
Health Positive
Safety Harbor, Florida, 34695, United States
Treasure Coast Infectious Disease Consultants
Vero Beach, Florida, 32960, United States
Triple O Research Institute, PA
West Palm Beach, Florida, 33401, United States
AIDS Research Consortium of Atlanta, Inc.
Atlanta, Georgia, 30308, United States
Chatham County Health Department
Savannah, Georgia, 31410, United States
Community Research Initiative of New England
Boston, Massachusetts, 02215, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
ID Care
Hillsborough, New Jersey, 08844, United States
Synergy First Medical PLLC
Brooklyn, New York, 11230, United States
Erie County Medical Center Corporation
Buffalo, New York, 14215, United States
Bisher Akil, M.D., A Medical Corporation
New York, New York, 10011, United States
Aaron Diamond AIDS Research Center
New York, New York, 10016, United States
ACRIA
New York, New York, 10018, United States
Jacobi Medical Center
New York, New York, 10461, United States
AIDS Care
Rochester, New York, 14607, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Rosedale Infectious Disease
Huntersville, North Carolina, 28078, United States
University of Cincinnati
Cincinnati, Ohio, 45267-0405, United States
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104, United States
North Texas Infectious Diesease Consultants
Dallas, Texas, 75246, United States
Therapeutic Concepts
Houston, Texas, 77004, United States
The University of Texas Health Science Center at Houston Medical School
Houston, Texas, 77030, United States
Univ. of Puerto Rico - ACTU
San Juan, PR, 935, Puerto Rico
University of Puerto Rico, School of Medicine, CEMI
San Juan, PR, 935, Puerto Rico
Clinical Research P.R., Inc.
Santurce, Puerto Rico, 909, Puerto Rico
Related Publications (3)
Sherman KE, Abdel-Hameed E, Rouster SD, Shata MTM, Blackard JT, Safaie P, Kroner B, Preiss L, Horn PS, Kottilil S. Improvement in Hepatic Fibrosis Biomarkers Associated With Chemokine Receptor Inactivation Through Mutation or Therapeutic Blockade. Clin Infect Dis. 2019 May 17;68(11):1911-1918. doi: 10.1093/cid/ciy807.
PMID: 30239650DERIVEDThompson M, Saag M, DeJesus E, Gathe J, Lalezari J, Landay AL, Cade J, Enejosa J, Lefebvre E, Feinberg J. A 48-week randomized phase 2b study evaluating cenicriviroc versus efavirenz in treatment-naive HIV-infected adults with C-C chemokine receptor type 5-tropic virus. AIDS. 2016 Mar 27;30(6):869-78. doi: 10.1097/QAD.0000000000000988.
PMID: 26636929DERIVEDKagan RM, Johnson EP, Siaw MF, Van Baelen B, Ogden R, Platt JL, Pesano RL, Lefebvre E. Comparison of genotypic and phenotypic HIV type 1 tropism assay: results from the screening samples of Cenicriviroc Study 202, a randomized phase II trial in treatment-naive subjects. AIDS Res Hum Retroviruses. 2014 Feb;30(2):151-9. doi: 10.1089/AID.2013.0123. Epub 2013 Aug 14.
PMID: 23875707DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 18, 2011
First Posted
April 20, 2011
Study Start
June 1, 2011
Primary Completion
December 1, 2012
Study Completion
June 1, 2013
Last Updated
July 10, 2013
Record last verified: 2013-07