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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

Thompson, Melanie; Saag, Michael; DeJesus, Edwin; Gathe, Joseph; Lalezari, Jay; Landay, Alan L.; Cade, Jerry; Enejosa, Jeffrey; Lefebvre, Eric; Feinberg, Judith

doi: 10.1097/QAD.0000000000000988
Clinical Science

Objective: To compare the efficacy, safety, and anti-inflammatory effects of cenicriviroc (CVC), an oral, once-daily C-C chemokine receptor types 5 and 2 antagonist, with those of efavirenz (EFV) in treatment-naive, HIV-1-infected adults.

Design: A 48-week, randomized, double-blind, double-dummy phase 2b trial at 43 institutions (USA and Puerto Rico).

Methods: Study participants (HIV-1 RNA ≥1000 copies/ml, CD4+ cell count ≥200 cells/μl, C-C chemokine receptor type 5-tropic virus) were randomized 2 : 2 : 1 to CVC 100 mg (CVC100), CVC 200 mg (CVC200), or EFV 600 mg, each administered with emtricitabine/tenofovir disoproxil fumarate. Key end points were virologic success (HIV-1 RNA <50 copies/ml) at week 24 (primary) and week 48 (secondary), safety/tolerability at weeks 24 and 48. Study sites and patients remained blinded until week 48.

Results: A total of 143 patients were randomized (CVC100, n = 59; CVC200, n = 56; EFV, n = 28). Virologic success was obtained at week 24 in 76, 73, and 71% of study participants for CVC100, CVC200, and EFV, respectively (all P > 0.05 versus EFV), and at week 48 in 68, 64, and 50%, respectively (all P > 0.05 versus EFV). Resistance mutations emerged in five and zero CVC and EFV-treated study participants, respectively. Virologic nonresponse and nucleoside reverse transcriptase inhibitor resistance decreased when CVC minimum plasma concentration was at least 47.8 ng/ml. Treatment-related adverse events of at least grade 2 and discontinuations because of adverse events were less frequent in CVC-treated study participants. Total and low-density lipoprotein cholesterol decreased with CVC, but increased with EFV. C-C chemokine ligand type 2 (CCL2) (aka monocyte chemotactic protein-1) increased in a dose-dependent manner, whereas soluble CD14 levels decreased with CVC.

Conclusion: CVC showed efficacy and favorable safety in treatment-naive HIV-1-infected study participants, supporting selection of CVC200 for phase 3 studies.

Trial registration: NCT01338883.

aAIDS Research Consortium of Atlanta, Atlanta, Georgia

bUniversity of Alabama at Birmingham, Birmingham, Alabama

cOrlando Immunology Center, Orlando, Florida

dTherapeutic Concepts, Houston, Texas

eQuest Clinical Research, San Francisco, California

fRush University, Chicago, Illinois

gNevada AIDS Research and Education Society, Las Vegas, Nevada

hTobira Therapeutics, Inc., South San Francisco, California

iUniversity of Cincinnati, Cincinnati, Ohio, USA.

Correspondence to Melanie Thompson, AIDS Research Consortium of Atlanta, 440 Ralph McGill Blvd., NE, Atlanta, GA 30312, USA. E-mail: drmt@mindspring.com

Received 24 July, 2015

Revised 26 November, 2015

Accepted 26 November, 2015

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