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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01338883
• Other study ID #: TBR-652-2-202
• Status: Completed
• Phase: Phase 2
• First received: April 18, 2011
• Last updated: July 3, 2013
• Start date: June 2011
• Est. completion date: June 2013

Study information

• Verified date: July 2013
• Source: Tobira Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: June 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Cenicriviroc 100 mg
100 mg CVC plus Truvada
• Cenicriviroc 200 mg + Truvada
200 mg CVC plus Truvada
• Sustiva + Truvada
Sustiva plus Truvada

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Tobira Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24		24 weeks	No