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

NCT ID: NCT01338883

Last Updated: 2013-07-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

143 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-30

Study Completion Date

2013-06-30

Brief Summary

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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

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Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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CVC 100 mg + Truvada

Group Type EXPERIMENTAL

Cenicriviroc 100 mg

Intervention Type DRUG

100 mg CVC plus Truvada

CVC 200 mg + Truvada

Group Type EXPERIMENTAL

Cenicriviroc 200 mg + Truvada

Intervention Type DRUG

200 mg CVC plus Truvada

Sustiva + Truvada

Group Type ACTIVE_COMPARATOR

Sustiva + Truvada

Intervention Type DRUG

Sustiva plus Truvada

Interventions

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Cenicriviroc 100 mg

100 mg CVC plus Truvada

Intervention Type DRUG

Cenicriviroc 200 mg + Truvada

200 mg CVC plus Truvada

Intervention Type DRUG

Sustiva + Truvada

Sustiva plus Truvada

Intervention Type DRUG

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tobira Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Southwest Center for HIV / AIDS

Phoenix, Arizona, United States

Site Status

AIDS Healthcare Foundation Research Center

Beverly Hills, California, United States

Site Status

Pacific Oaks Medical Group

Beverly Hills, California, United States

Site Status

Providence Clinical Research

Burbank, California, United States

Site Status

AIDS Research Alliance

Los Angeles, California, United States

Site Status

Peter J Ruane MD Incorporated

Los Angeles, California, United States

Site Status

Oasis Clinic

Los Angeles, California, United States

Site Status

Anthony Mills

Los Angeles, California, United States

Site Status

Orange Coast Medical Group

Newport Beach, California, United States

Site Status

Stanford University ACTU

Palo Alto, California, United States

Site Status

University of California at San Francisco

San Francisco, California, United States

Site Status

Quest Clinical Research

San Francisco, California, United States

Site Status

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Whitman-Walker Clinic

Washington D.C., District of Columbia, United States

Site Status

Therafirst Medical Center

Fort Lauderdale, Florida, United States

Site Status

Gary Richmond

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

University of Miami School of Medicine

Miami, Florida, United States

Site Status

Care Resource Inc.

Miami, Florida, United States

Site Status

Kinder Medical Group

Miami, Florida, United States

Site Status

Wohlfeiler, Piperato & Associates, LLC

Miami Beach, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

Health Positive

Safety Harbor, Florida, United States

Site Status

Treasure Coast Infectious Disease Consultants

Vero Beach, Florida, United States

Site Status

Triple O Research Institute, PA

West Palm Beach, Florida, United States

Site Status

AIDS Research Consortium of Atlanta, Inc.

Atlanta, Georgia, United States

Site Status

Chatham County Health Department

Savannah, Georgia, United States

Site Status

Community Research Initiative of New England

Boston, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

ID Care

Hillsborough, New Jersey, United States

Site Status

Synergy First Medical PLLC

Brooklyn, New York, United States

Site Status

Erie County Medical Center Corporation

Buffalo, New York, United States

Site Status

Bisher Akil, M.D., A Medical Corporation

New York, New York, United States

Site Status

Aaron Diamond AIDS Research Center

New York, New York, United States

Site Status

ACRIA

New York, New York, United States

Site Status

Jacobi Medical Center

New York, New York, United States

Site Status

AIDS Care

Rochester, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Rosedale Infectious Disease

Huntersville, North Carolina, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

University of Pennsylvania Health System

Philadelphia, Pennsylvania, United States

Site Status

North Texas Infectious Diesease Consultants

Dallas, Texas, United States

Site Status

Therapeutic Concepts

Houston, Texas, United States

Site Status

The University of Texas Health Science Center at Houston Medical School

Houston, Texas, United States

Site Status

Univ. of Puerto Rico - ACTU

San Juan, PR, Puerto Rico

Site Status

University of Puerto Rico, School of Medicine, CEMI

San Juan, PR, Puerto Rico

Site Status

Clinical Research P.R., Inc.

Santurce, Puerto Rico, Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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.

Reference Type DERIVED
PMID: 30239650 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26636929 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23875707 (View on PubMed)

Other Identifiers

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TBR-652-2-202

Identifier Type: -

Identifier Source: org_study_id

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