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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01338883
First received: April 18, 2011
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
HIV-1 Infection
Drug: Cenicriviroc 100 mg
Drug: Cenicriviroc 200 mg + Truvada
Drug: Sustiva + Truvada
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tobira Therapeutics, Inc.:

Primary Outcome Measures:
  • To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 143
Study Start Date: June 2011
Study Completion Date: June 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CVC 100 mg + Truvada Drug: Cenicriviroc 100 mg
100 mg CVC plus Truvada
Experimental: CVC 200 mg + Truvada Drug: Cenicriviroc 200 mg + Truvada
200 mg CVC plus Truvada
Active Comparator: Sustiva + Truvada Drug: Sustiva + Truvada
Sustiva plus Truvada

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01338883

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Southwest Center for HIV / AIDS
Phoenix, Arizona, United States, 85006
United States, California
AIDS Healthcare Foundation Research Center
Beverly Hills, California, United States, 90211
Pacific Oaks Medical Group
Beverly Hills, California, United States, 90211
Providence Clinical Research
Burbank, California, United States, 91505
AIDS Research Alliance
Los Angeles, California, United States, 90015
Peter J Ruane MD Incorporated
Los Angeles, California, United States, 90036
Oasis Clinic
Los Angeles, California, United States, 90059
Anthony Mills
Los Angeles, California, United States, 90069
Orange Coast Medical Group
Newport Beach, California, United States, 92663
Stanford University ACTU
Palo Alto, California, United States, 94304
University of California at San Francisco
San Francisco, California, United States, 94110
Quest Clinical Research
San Francisco, California, United States, 94115
United States, District of Columbia
Whitman-Walker Clinic
Washington, District of Columbia, United States, 20009
Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Florida
Midway Immunology and Research Center
Fort Pierce, Florida, United States, 34982
Therafirst Medical Center
Ft. Lauderdale, Florida, United States, 33308
Gary Richmond
Ft. Lauderdale, Florida, United States, 33316
Care Resource Inc.
Miami, Florida, United States, 33137
Kinder Medical Group
Miami, Florida, United States, 33137
University of Miami School of Medicine
Miami, Florida, United States, 33136
Wohlfeiler, Piperato & Associates, LLC
Miami Beach, Florida, United States, 33139
Orlando Immunology Center
Orlando, Florida, United States, 32803
Health Positive
Safety Harbor, Florida, United States, 34695
Treasure Coast Infectious Disease Consultants
Vero Beach, Florida, United States, 32960
Triple O Research Institute, PA
West Palm Beach, Florida, United States, 33401
United States, Georgia
AIDS Research Consortium of Atlanta, Inc.
Atlanta, Georgia, United States, 30308
Chatham County Health Department
Savannah, Georgia, United States, 31410
United States, Massachusetts
Community Research Initiative of New England
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New Jersey
ID Care
Hillsborough, New Jersey, United States, 08844
United States, New York
Synergy First Medical PLLC
Brooklyn, New York, United States, 11230
Erie County Medical Center Corporation
Buffalo, New York, United States, 14215
Bisher Akil, M.D., A Medical Corporation
New York, New York, United States, 10011
ACRIA
New York, New York, United States, 10018
Aaron Diamond AIDS Research Center
New York, New York, United States, 10016
Jacobi Medical Center
New York City, New York, United States, 10461
AIDS Care
Rochester, New York, United States, 14607
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Rosedale Infectious Disease
Huntersville, North Carolina, United States, 28078
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267-0405
United States, Pennsylvania
University of Pennsylvania Health System
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
North Texas Infectious Diesease Consultants
Dallas, Texas, United States, 75246
Therapeutic Concepts
Houston, Texas, United States, 77004
The University of Texas Health Science Center at Houston Medical School
Houston, Texas, United States, 77030
Puerto Rico
Univ. of Puerto Rico - ACTU
San Juan, Puerto Rico, 935
University of Puerto Rico, School of Medicine, CEMI
San Juan, Puerto Rico, 935
Clinical Research P.R., Inc.
Santurce, Puerto Rico, 909
Sponsors and Collaborators
Tobira Therapeutics, Inc.
  More Information

No publications provided by Tobira Therapeutics, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01338883     History of Changes
Other Study ID Numbers: TBR-652-2-202
Study First Received: April 18, 2011
Last Updated: July 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Tobira Therapeutics, Inc.:
HIV-1 Infection
CCR5-tropic
Anti-retroviral naive

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Efavirenz
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 23, 2014