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

Phase 2

Completed

• Conditions: HIV-1 Infection
• Interventions: Drug: Cenicriviroc 100 mg; Drug: Cenicriviroc 200 mg + Truvada; Drug: Sustiva + Truvada

• Registration Number: NCT01338883
• Lead Sponsor: Tobira Therapeutics, Inc.

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 available

Study Timeline

• Study First Submitted: 2011-04-18
• Study First Submitted QC: 2011-04-19
• Study First Posted: 2011-04-20
• Study Start: 2011-06
• Primary Completion: 2012-12
• Study Completion: 2013-06
• Disposition First Submitted: 2013-06-19
• Status Verified: 2013-07
• Disposition First Submitted QC: 2013-07-03
• Last Update Submitted: 2013-07-03
• Disposition First Posted: 2013-07-10
• Last Update Posted: 2013-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 143

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CVC 100 mg + Truvada	Cenicriviroc 100 mg	-
CVC 200 mg + Truvada	Cenicriviroc 200 mg + Truvada	-
Sustiva + Truvada	Sustiva + Truvada	-

Primary Outcome Measures

Name	Time	Method
To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24	24 weeks

Trial Locations

Locations (48)

Oasis Clinic; 🇺🇸 Los Angeles, California, United States

Anthony Mills; 🇺🇸 Los Angeles, California, United States

Providence Clinical Research; 🇺🇸 Burbank, California, United States

AIDS Research Alliance; 🇺🇸 Los Angeles, California, United States

Orange Coast Medical Group; 🇺🇸 Newport Beach, California, United States

AIDS Research Consortium of Atlanta, Inc.; 🇺🇸 Atlanta, Georgia, United States

Peter J Ruane MD Incorporated; 🇺🇸 Los Angeles, California, United States

North Texas Infectious Diesease Consultants; 🇺🇸 Dallas, Texas, United States

University of Miami School of Medicine; 🇺🇸 Miami, Florida, United States

Community Research Initiative of New England; 🇺🇸 Boston, Massachusetts, United States

The University of Texas Health Science Center at Houston Medical School; 🇺🇸 Houston, Texas, United States

Therapeutic Concepts; 🇺🇸 Houston, Texas, United States

Clinical Research P.R., Inc.; 🇵🇷 Santurce, Puerto Rico

Treasure Coast Infectious Disease Consultants; 🇺🇸 Vero Beach, Florida, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Southwest Center for HIV / AIDS; 🇺🇸 Phoenix, Arizona, United States

University of California at San Francisco; 🇺🇸 San Francisco, California, United States

Quest Clinical Research; 🇺🇸 San Francisco, California, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Health Positive; 🇺🇸 Safety Harbor, Florida, United States

AIDS Healthcare Foundation Research Center; 🇺🇸 Beverly Hills, California, United States

Pacific Oaks Medical Group; 🇺🇸 Beverly Hills, California, United States

Stanford University ACTU; 🇺🇸 Palo Alto, California, United States

Whitman-Walker Clinic; 🇺🇸 Washington, District of Columbia, United States

Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

Therafirst Medical Center; 🇺🇸 Ft. Lauderdale, Florida, United States

Wohlfeiler, Piperato & Associates, LLC; 🇺🇸 Miami Beach, Florida, United States

Care Resource Inc.; 🇺🇸 Miami, Florida, United States

Midway Immunology and Research Center; 🇺🇸 Fort Pierce, Florida, United States

Gary Richmond; 🇺🇸 Ft. Lauderdale, Florida, United States

Kinder Medical Group; 🇺🇸 Miami, Florida, United States

Orlando Immunology Center; 🇺🇸 Orlando, Florida, United States

Triple O Research Institute, PA; 🇺🇸 West Palm Beach, Florida, United States

Chatham County Health Department; 🇺🇸 Savannah, Georgia, United States

ID Care; 🇺🇸 Hillsborough, New Jersey, United States

Erie County Medical Center Corporation; 🇺🇸 Buffalo, New York, United States

Jacobi Medical Center; 🇺🇸 New York City, New York, United States

Synergy First Medical PLLC; 🇺🇸 Brooklyn, New York, United States

ACRIA; 🇺🇸 New York, New York, United States

Bisher Akil, M.D., A Medical Corporation; 🇺🇸 New York, New York, United States

Aaron Diamond AIDS Research Center; 🇺🇸 New York, New York, United States

AIDS Care; 🇺🇸 Rochester, New York, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Rosedale Infectious Disease; 🇺🇸 Huntersville, North Carolina, United States

University of Pennsylvania Health System; 🇺🇸 Philadelphia, Pennsylvania, United States

Univ. of Puerto Rico - ACTU; 🇵🇷 San Juan, Puerto Rico

University of Puerto Rico, School of Medicine, CEMI; 🇵🇷 San Juan, Puerto Rico