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

• ClinicalTrials.gov Identifier: NCT01338883
• Recruitment Status: Completed
• First Posted: April 20, 2011
• Last Update Posted: July 10, 2013
• Sponsor: Tobira Therapeutics, Inc.
• Information provided by (Responsible Party): Tobira Therapeutics, Inc.

Tracking Information

• First Submitted Date: April 18, 2011
• First Posted Date: April 20, 2011
• Last Update Posted Date: July 10, 2013
• Study Start Date: June 2011
• Actual Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 19, 2011): To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24 [ Time Frame: 24 weeks ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: HIV-1 Infection

Intervention

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

Study Arms

• Experimental: CVC 100 mg + Truvada
  Intervention: Drug: Cenicriviroc 100 mg
• Experimental: CVC 200 mg + Truvada
  Intervention: Drug: Cenicriviroc 200 mg + Truvada
• Active Comparator: Sustiva + Truvada
  Intervention: Drug: Sustiva + Truvada

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 3, 2013): 143
• Original Estimated Enrollment (submitted: April 19, 2011): 150
• Actual Study Completion Date: June 2013
• Actual Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT01338883
• Other Study ID Numbers: TBR-652-2-202
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Tobira Therapeutics, Inc.
• Study Sponsor: Tobira Therapeutics, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Tobira Therapeutics, Inc.
• Verification Date: July 2013