A Study to Evaluate the Effects of Cenicriviroc Mesylate on Arterial Inflammation in People Living With HIV

A Limited-Center, Prospective, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Cenicriviroc Mesylate on Arterial Inflammation in People Living With HIV

The study was conducted to determine if cenicriviroc mesylate (CVC) would decrease vascular inflammation as measured by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging of the aorta and carotid arteries.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection; Elevated Cardiovascular Risk
• Intervention / Treatment: Drug: CVC 150 mg; Drug: CVC 300 mg; Other: Placebo for CVC 150 mg; Other: Placebo for CVC 300 mg

Detailed Description

This was a double-blind, placebo-controlled phase II clinical trial comparing the intervention of CVC versus placebo for a duration of 24 weeks on arterial inflammation evaluated by FDG-PET/CT imaging.

A total of 110 participants were randomized 2:1 to the CVC arm (Arm A) or placebo for CVC arm (Arm B). Stratification by statin use at randomization ensured even distribution of statin use between the treatment groups.

Analyses were based on the efficacy population: all enrolled participants who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.

Analysis of the primary outcome utilized multiple imputation by regression to impute missing data.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90035
      • University of California, Los Angeles CARE Center CRS (Site # 601)
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center CRS (Site # 701)
    • San Francisco, California, United States, 94110
      • UCSF HIV/AIDS CRS (Site # 801)
    • Torrance, California, United States, 90502
      • Harbor University of California Los Angeles Center CRS (Site # 603)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS (Site # 2701)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital CRS (MGH CRS) (Site # 101)
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital Therapeutics (BWH TCRS) CRS (Site # 107)
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1010
      • Washington University Therapeutics (WT) CRS (Site # 2101)
  • New York
    • New York, New York, United States, 10010
      • Weill Cornell Chelsea CRS (Site # 7804)
    • New York, New York, United States, 10065
      • Weill Cornell Uptown CRS (Site # 7803)
    • Rochester, New York, United States, 14642
      • University of Rochester Adult HIV Therapeutic Strategies Network CRS (Site # 31787)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7215
      • Chapel Hill CRS (Site # 3201)
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0405
      • Cincinnati CRS (Site # 2401)
    • Cleveland, Ohio, United States, 44106
      • Case CRS (Site # 2501)
    • Columbus, Ohio, United States, 43210-1282
      • Ohio State University CRS (Site # 2301)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh CRS (Site # 1001)
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Therapeutics (VT) CRS (Site # 3652)
  • Texas
    • Houston, Texas, United States, 77030
      • Houston AIDS Research Team CRS (Site # 31473)
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington Positive Research CRS (Site # 1401)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Documented to be living with HIV-1 infection.
2. Currently on a stable, continuous NNRTI-based or unboosted INSTI-based ART regimen for ≥48 weeks prior to study entry with no plans to change ART during the course of the study.
3. At least a year of controlled HIV-1 RNA levels.
4. Current CD4+ cell count >200 cells/mm^3.

5. Elevated cardiovascular risk defined as at least one of the following:

   • Clinical atherosclerotic disease (symptomatic atherosclerotic lesions in any vessel)
   • Subclinical atherosclerotic disease (coronary artery calcification [CAC] >10 or presence of non-obstructive plaques)
   • Diabetes mellitus (DM) or prediabetes
   • Obesity
   • Hypertension or blood pressure ≥130/80 mmHg
   • Elevated LDL cholesterol (fasting LDL of >160 mg/dL)
   • Low HDL cholesterol (<40 mg/dL)
   • Current tobacco smoking
   • Family history of premature coronary artery disease (CAD)
   • hsCRP >2.0 mg/L

Key Exclusion Criteria:

1. Acute coronary syndrome
2. A current diagnosis of latent or active tuberculosis (TB) infection
3. Current diagnosis with other intracellular pathogens (Mycobacterium avium complex, Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus neoformans).
4. Untreated hepatitis B virus (HBV) infection
5. Current hepatitis C virus (HCV) infection
6. Current, acute or clinically significant infection or illness requiring IV antibiotics or hospitalization
7. History of cirrhosis with severe hepatic impairment and/or hepatic decompensation
8. Active malignancy, except squamous cell skin cancer.
9. Hemoglobin A1c >8% within 90 days prior to study entry.
10. Initiation of statin therapy or change in statin dose within 90 days prior to study entry.

11. Current use of any of the statins at the doses indicated:

    • Atorvastatin, >40 mg/day dose
    • Rosuvastatin, ≥20 mg/day dose
12. Concurrent use of drugs with potential drug-drug interactions with CVC within 90 days prior to study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CVC arm (Arm A); Participants with pre-existing ART regimen of efavirenz (EFV) took CVC 300 mg. Participants with all other pre-existing ART regimens took CVC 150 mg.	Drug: CVC 150 mg; Administered as one 150-mg tablet by mouth once a day with food.; Drug: CVC 300 mg; Administered as two 150-mg tablets by mouth once a day with food.
Placebo Comparator: Placebo for CVC arm (Arm B); Participants with pre-existing ART regimen of efavirenz (EFV) took placebo for CVC 300 mg. Participants with all other pre-existing ART regimens took placebo for CVC 150 mg.	Other: Placebo for CVC 150 mg; Administered as one 150-mg matching placebo tablets by mouth once a day with food.; Other: Placebo for CVC 300 mg; Administered as two 150-mg matching placebo tablets by mouth once a day with food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change (Expressed as Ratio to Baseline) in 18-FDG-PET Target-to-background Ratio (TBR) of the Most Diseased Segment (MDS) of the Index (Most-inflamed) Vessel.	Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standardized Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR means a reduction in the target arterial wall inflammation over time. Index vessel is the vessel with the highest vessel TBR at baseline. The most diseased segment is the approximately 1-cm section of the vessel with the highest activity at baseline. The results are expressed as the ratio of TBR at week 24 to baseline. For the statistical analyses, results for the 6 and 9 missing values in Arm A and Arm B, respectively, were imputed using multiple imputation by regression.	Measured at baseline and week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs)	Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standard Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of TBR at week 24 to baseline.	Measured at baseline and week 24
Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta	Standard Uptake Value (SUV) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid). Specifically, it is the average of all evaluable SUV for a given arterial vessel. A negative number for the change in SUV implies a reduction in the target arterial wall inflammation over time. The results are expressed as the ratio of SUV at week 24 to baseline.	Measured at baseline and week 24
Change in Fasting Glucose	Fasting glucose (mg/dL) measures the level of sugar (glucose) in the blood after fasting (no eating or drinking except water) for at least 8 hours. Higher value of change means an increase in glucose levels over time. The results are expressed as the change in fasting glucose from baseline to week 24.	Measured at baseline and week 24
Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR)	Insulin is a hormone crucial in regulating blood sugar levels. HOMA-IR is a calculation used to assess insulin resistance and is calculated with the formula: insulin (uIU/mL) * glucose (mg/dL) / 405. Higher value of change in insulin and HOMA-IR means an increase in insulin resistance over time. The results are expressed as the ratio of fasting insulin or HOMA-IR at week 24 to baseline.	Measured at baseline and week 24
Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1)	The cytokine, Interleukin-6 (IL-6, pg/mL); protein, high-sensitivity C Reactive Protein (hsCRP, mg/L); and chemokine, monocyte chemoattractant protein-1 (MCP-1, pg/mL) are all markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. MCP-1 is a ligand of CCR2 that was expected to increase with CVC. The results are expressed as the ratio of hsCRP, IL-6, or MCP-1 at week 24 to baseline.	Measured at baseline and week 24
Change in Biomarkers of Immune Activation (sCD14 and sCD163)	The soluble proteins soluble-CD14 (sCD14, ng/mL) and soluble-CD163 (sCD163, ng/mL) are all markers of monocyte/macrophage activation. Higher value of change means an increase in the biomarker levels over time. Higher levels of sCD14 and sCD163 occur in response to inflammation and infection. The results are expressed as the difference between sCD14 or sCD163 from baseline to week 24.	Measured at baseline and week 24
Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta)	The chemokines macrophage inflammatory protein-1 alpha and beta (MIP-1 alpha and beta, pg/mL) as well as the chemokine, RANTES (ng/mL), are markers of inflammation. Higher value of change means an increase in the biomarker levels over time. Higher levels of these biomarkers indicates inflammation. RANTES and MIP-1 beta are ligands of CCR5 that were expected to increase with CVC. The results are expressed as the ratio of RANTES or MIP-1 beta at week 24 to baseline.	Measured at baseline and week 24

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: AbbVie
• Investigators: Study Chair: Janet Lo, MD, MMSc, Massachusetts General Hospital

Publications and helpful links

Helpful Links

• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
• Specific table used in the study protocol. For example, "The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009)."

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Actual): June 19, 2024
• Study Completion (Actual): June 19, 2024

Study Registration Dates

• First Submitted: November 10, 2022
• First Submitted That Met QC Criteria: November 22, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: HIV; Vascular Inflammation
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Vasculitis; Inflammation; Arteritis
• Other Study ID Numbers: A5415

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Results will be published in a manuscript and supporting information submitted to NHLBI BioData Catalyst® (BDC) (including data dictionaries and case report forms).
• IPD Sharing Time Frame: Within 3 years of final participant follow-up.
• IPD Sharing Access Criteria: Data will be available by request in the NHLBI repository.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No