Clinical trial NCT01338883: 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: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Keywords: HIV-1 Infection
CCR5-tropic
Anti-retroviral naive
Lead sponsor: Tobira Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-20
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Selected Inclusion Criteria:

1. Adult male and female, HIV-1-infected patients 18 years old and older.
2. Body mass index (BMI) 18 to \< 35 kg/m2.
3. 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.
4. HIV-1 CCR5-tropic-only virus.
5. Plasma HIV-1 RNA level \>/=1,000 copies/mL at first Screening.
6. CD4 cell count \>/=250 cells/mm3 at first Screening.

Selected Exclusion Criteria:

1. Presence of CXCR4- or dual/mixed-tropic HIV-1 virus.
2. Presence of primary resistance mutations or phenotypic resistance to TDF, FTC, or EFV and/or mutations associated with multidrug nucleoside/nucleotide resistance.
3. An active CDC category C disease (except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial).
4. Any historical CD4 count \< 200 cells/mm3.
5. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value Grade \> 2 or total bilirubin greater than the upper limit of normal (ULN).
6. 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.

Primary outcomes:
measure: To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Southwest Center for HIV / AIDS
state: Arizona
city: Beverly Hills
country: United States
facility: AIDS Healthcare Foundation Research Center
state: California
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Burbank
country: United States
facility: Providence Clinical Research
state: California
city: Los Angeles
country: United States
facility: AIDS Research Alliance
state: California
city: Los Angeles
country: United States
facility: Peter J Ruane MD Incorporated
state: California
city: Los Angeles
country: United States
facility: Oasis Clinic
state: California
city: Los Angeles
country: United States
facility: Anthony Mills
state: California
city: Newport Beach
country: United States
facility: Orange Coast Medical Group
state: California
city: Palo Alto
country: United States
facility: Stanford University ACTU
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Whitman-Walker Clinic
state: District of Columbia
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Ft. Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Ft. Lauderdale
country: United States
facility: Gary Richmond
state: Florida
city: Miami Beach
country: United States
facility: Wohlfeiler, Piperato & Associates, LLC
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Miami
country: United States
facility: Care Resource Inc.
state: Florida
city: Miami
country: United States
facility: Kinder Medical Group
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Safety Harbor
country: United States
facility: Health Positive
state: Florida
city: Vero Beach
country: United States
facility: Treasure Coast Infectious Disease Consultants
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, PA
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta, Inc.
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Hillsborough
country: United States
facility: ID Care
state: New Jersey
city: Brooklyn
country: United States
facility: Synergy First Medical PLLC
state: New York
city: Buffalo
country: United States
facility: Erie County Medical Center Corporation
state: New York
city: New York City
country: United States
facility: Jacobi Medical Center
state: New York
city: New York
country: United States
facility: Bisher Akil, M.D., A Medical Corporation
state: New York
city: New York
country: United States
facility: Aaron Diamond AIDS Research Center
state: New York
city: New York
country: United States
facility: ACRIA
state: New York
city: Rochester
country: United States
facility: AIDS Care
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Infectious Disease
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Dallas
country: United States
facility: North Texas Infectious Diesease Consultants
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston Medical School
state: Texas
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico - ACTU
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico, School of Medicine, CEMI
city: Santurce
country: Puerto Rico
facility: Clinical Research P.R., Inc.
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.