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

NCT05630885 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: A5415
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 19

Brief Summary

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.

Conditions

HIV-1-infection; Elevated Cardiovascular Risk

Keywords

HIV; Vascular Inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs)

  Measured at baseline and week 24

• Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta

  Measured at baseline and week 24

• Change in Fasting Glucose

  Measured at baseline and week 24

• Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR)

  Measured at baseline and week 24

• Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1)

  Measured at baseline and week 24

Study Arms (2)

CVC arm (Arm A)

EXPERIMENTAL

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; Drug: CVC 300 mg

Placebo for CVC arm (Arm B)

PLACEBO COMPARATOR

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; Other: Placebo for CVC 300 mg

Interventions

CVC 150 mg DRUG

Administered as one 150-mg tablet by mouth once a day with food.

CVC arm (Arm A)

CVC 300 mg DRUG

Administered as two 150-mg tablets by mouth once a day with food.

CVC arm (Arm A)

Placebo for CVC 150 mg OTHER

Administered as one 150-mg matching placebo tablets by mouth once a day with food.

Placebo for CVC arm (Arm B)

Placebo for CVC 300 mg OTHER

Administered as two 150-mg matching placebo tablets by mouth once a day with food.

Placebo for CVC arm (Arm B)

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented to be living with HIV-1 infection.
• 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.
• At least a year of controlled HIV-1 RNA levels.
• Current CD4+ cell count \>200 cells/mm\^3.
• 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

You may not qualify if:

• Acute coronary syndrome
• A current diagnosis of latent or active tuberculosis (TB) infection
• Current diagnosis with other intracellular pathogens (Mycobacterium avium complex, Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus neoformans).
• Untreated hepatitis B virus (HBV) infection
• Current hepatitis C virus (HCV) infection
• Current, acute or clinically significant infection or illness requiring IV antibiotics or hospitalization
• History of cirrhosis with severe hepatic impairment and/or hepatic decompensation
• Active malignancy, except squamous cell skin cancer.
• Hemoglobin A1c \>8% within 90 days prior to study entry.
• Initiation of statin therapy or change in statin dose within 90 days prior to study entry.
• Current use of any of the statins at the doses indicated:
• Atorvastatin, \>40 mg/day dose
• Rosuvastatin, ≥20 mg/day dose
• Concurrent use of drugs with potential drug-drug interactions with CVC within 90 days prior to study entry.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• AbbVie: collaborator

Study Sites (19)

University of California, Los Angeles CARE Center CRS (Site # 601)

Los Angeles, California, 90035, United States

Location

UCSD Antiviral Research Center CRS (Site # 701)

San Diego, California, 92103, United States

Location

UCSF HIV/AIDS CRS (Site # 801)

San Francisco, California, 94110, United States

Location

Harbor University of California Los Angeles Center CRS (Site # 603)

Torrance, California, 90502, United States

Location

Northwestern University CRS (Site # 2701)

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital CRS (MGH CRS) (Site # 101)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital Therapeutics (BWH TCRS) CRS (Site # 107)

Boston, Massachusetts, 02115, United States

Location

Washington University Therapeutics (WT) CRS (Site # 2101)

St Louis, Missouri, 63110-1010, United States

Location

Weill Cornell Chelsea CRS (Site # 7804)

New York, New York, 10010, United States

Location

Weill Cornell Uptown CRS (Site # 7803)

New York, New York, 10065, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS (Site # 31787)

Rochester, New York, 14642, United States

Location

Chapel Hill CRS (Site # 3201)

Chapel Hill, North Carolina, 27599-7215, United States

Location

Cincinnati CRS (Site # 2401)

Cincinnati, Ohio, 45267-0405, United States

Location

Case CRS (Site # 2501)

Cleveland, Ohio, 44106, United States

Location

Ohio State University CRS (Site # 2301)

Columbus, Ohio, 43210-1282, United States

Location

University of Pittsburgh CRS (Site # 1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Therapeutics (VT) CRS (Site # 3652)

Nashville, Tennessee, 37204, United States

Location

Houston AIDS Research Team CRS (Site # 31473)

Houston, Texas, 77030, United States

Location

University of Washington Positive Research CRS (Site # 1401)

Seattle, Washington, 98104, United States

Location

Related Links

• 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)."
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Janet Lo, MD, MMSc

  Massachusetts General Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: At study entry, participants were randomized 2:1 to oral CVC (Arm A) or oral placebo for CVC (Arm B) once a day. The study treatment was added to the participants' pre-existing antiretroviral treatment (ART) regimens.

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: November 30, 2022
• Study Start: May 30, 2023
• Primary Completion: June 19, 2024
• Study Completion: June 19, 2024
• Last Updated: July 16, 2025
• Results First Posted: July 16, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Within 3 years of final participant follow-up.
• Access Criteria: Data will be available by request in the NHLBI repository.

Locations

US (19)