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

Tracking Information
First Submitted Date ICMJE	April 18, 2011
First Posted Date ICMJE	April 20, 2011
Last Update Posted Date	July 10, 2013
Study Start Date ICMJE	June 2011
Actual Primary Completion Date	December 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 19, 2011)	To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24 [ Time Frame: 24 weeks ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01338883 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	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
Official Title ICMJE	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
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	HIV-1 Infection
Intervention ICMJE	Drug: Cenicriviroc 100 mg 100 mg CVC plus Truvada; Drug: Cenicriviroc 200 mg + Truvada 200 mg CVC plus Truvada; Drug: Sustiva + Truvada Sustiva plus Truvada
Study Arms	Experimental: CVC 100 mg + Truvada Intervention: Drug: Cenicriviroc 100 mg; Experimental: CVC 200 mg + Truvada Intervention: Drug: Cenicriviroc 200 mg + Truvada; Active Comparator: Sustiva + Truvada Intervention: Drug: Sustiva + Truvada
Publications *	Thompson 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.; Kagan 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 3, 2013)	143
Original Estimated Enrollment ICMJE; (submitted: April 19, 2011)	150
Actual Study Completion Date	June 2013
Actual Primary Completion Date	December 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Selected Inclusion Criteria: 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. Selected Exclusion Criteria: 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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Puerto Rico, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01338883
Other Study ID Numbers ICMJE	TBR-652-2-202
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Tobira Therapeutics, Inc.
Study Sponsor ICMJE	Tobira Therapeutics, Inc.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Tobira Therapeutics, Inc.
Verification Date	July 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP