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

NCT04334915 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: ACTG A536332389
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the effects of cenicriviroc mesylate (CVC) on arterial inflammation in people living with HIV.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Change in arterial most diseased segment (MDS) 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) target-to-background ratio (TBR), measured in the carotid arteries and aorta.

  The standardized uptake value (SUV) of FDG will be measured in the carotid arteries, aortic root, and the left main coronary artery. The SUV is the decay-corrected tissue concentration of FDG (in kBq/mL) divided by the injected dose per body weight (kBq/g). TBR will be calculated for each vascular segment as the segment SUV divided by mean venous blood SUV. Change from baseline to week 24, where baseline is defined as pre-entry.

  Pre-entry and week 24

Secondary Outcomes (8)

• Change in aortic TBR (and other TBRs)

  Pre-entry and week 24

• Change in SUV measured in the carotid arteries and aorta

  Pre-entry and week 24

• Change in fasting glucose

  Entry and week 24

• Change in HOMA-IR

  Entry and week 24

• Change in sCD14

  Pre-entry, entry, week 22, and week 24

Study Arms (2)

Arm A: Cenicriviroc Mesylate (CVC)

EXPERIMENTAL

Cenicriviroc mesylate (CVC) 150 mg tablet once a day for at least 24 weeks will be added to the participants' pre-existing antiretroviral (ARV) regimens. For participants who are on an efavirenz (EFV)-based regimen, dosing will be 300 mg, administered as two 150-mg tablets, once a day.

Drug: Cenicriviroc Mesylate (CVC)

Arm B: Placebo for CVC

PLACEBO COMPARATOR

Placebo for CVC 150 mg tablet once a day for at least 24 weeks will be added to the participants' pre-existing ARV regimens. For participants who are on an EFV-based regimen, dosing will be 300 mg, administered as two 150-mg tablets, once a day.

Drug: Placebo

Interventions

Cenicriviroc Mesylate (CVC) DRUG

Administered orally

Arm A: Cenicriviroc Mesylate (CVC)

Placebo DRUG

Administered orally

Arm B: Placebo for CVC

Eligibility Criteria

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

You may qualify if:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load OR two HIV-1 RNA \>1,000 copies/mL.
• NOTE: The term "licensed" refers to a US Food and Drug Administration (FDA)-approved kit, which is required for all investigational new drug (IND) studies.
• WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
• Currently on a stable, continuous non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or unboosted integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen for ≥48 weeks prior to study entry with no ART interruption longer than 7 consecutive days and with no plans to change ART during the course of the study.
• NOTE A: Stable is defined as no within-class changes in ART regimen within 12 weeks prior to study entry and no between-class changes for 24 weeks prior to study entry.
• NOTE B: Unboosted ART is defined as an ART regimen that does not include the pharmacologic booster COBI or RTV.
• NOTE C: Modifications of ART formulation within 12 weeks prior to study entry (e.g., from standard formulation to fixed-dose combination of the same drugs), are permitted.
• Screening HIV-1 RNA level below the limit of quantification (e.g., \<20, \<40, \<50, or \<75 copies/mL, depending on the assay) using an FDA-approved assay with a quantification limit of 75 copies/mL or lower performed by any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent within 90 days prior to study entry.
• All HIV-1 RNA levels within 48 weeks prior to study entry below the limit of quantification (e.g., \<20, \<40, \<50, or \<75 copies/mL, depending on the assay) using an FDA-approved assay with a quantification limit of 75 copies/mL or lower performed by any laboratory that has a CLIA certification or its equivalent.
• NOTE A: Up to two HIV-1 RNA determinations that are between the assay quantification limit and 500 copies/mL (i.e., "blips") are allowed as long as the preceding and subsequent determinations are below the level of quantification.
• NOTE B: The screening value may serve as the subsequent undetectable value following a blip.
• CD4+ cell count \>200 cells/mm\^3 obtained within 90 days prior to study entry at any US laboratory that has a CLIA certification or its equivalent.
• At least one of the following cardiovascular risk factors (current diagnosis or receiving treatment, except where a time period is specified):
• Clinical atherosclerotic disease (symptomatic atherosclerotic lesions in any vessel)
• Subclinical atherosclerotic disease (coronary artery calcification \[CAC\] \>10 or presence of non-obstructive plaques)

You may not qualify if:

• Acute coronary syndrome, defined as myocardial infarction (MI) or unstable angina, within 90 days prior to study entry.
• A current diagnosis of latent or active tuberculosis (TB) infection, any prior untreated TB infection, inadequate treatment of active TB, or inadequate treatment of latent TB.
• NOTE A: Individuals with cases of active infection and latent TB infection with a history of adequate treatment may be considered for enrollment provided the individual has a negative chest X-ray following treatment and within 1 year prior to study entry.
• NOTE B: Written documentation of prior TB treatment and negative chest x-ray is required.
• Current diagnosis with other intracellular pathogens (Mycobacterium avium complex, Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus neoformans) within 90 days prior to study entry.
• Untreated hepatitis B virus (HBV) infection with detectable HBV DNA within 6 months prior to study entry.
• Current hepatitis C virus (HCV) infection (i.e., detectable HCV RNA within 6 months prior to study entry).
• Acute or clinically significant infection or illness requiring IV antibiotics or hospitalization within 90 days prior to study entry.
• History of cirrhosis with severe hepatic impairment and/or hepatic decompensation including ascites, hepatic encephalopathy, or variceal bleeding.
• Prior or planned liver transplantation.
• Active malignancy, except squamous cell skin cancer
• More than two HIV-1 RNA determinations ≥500 copies/mL within 48 weeks prior to study entry.
• Hemoglobin A1c \>8% within 90 days prior to study entry by any laboratory that has a CLIA certification or its equivalent.
• 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:

Sponsors & Collaborators

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

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Janet Lo, MD, MMSc

  Massachusetts General Hospital

  STUDY CHAIR

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

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 6, 2020
• Study Start: November 22, 2022
• Primary Completion: August 15, 2024
• Study Completion: August 15, 2024
• Last Updated: December 21, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? * To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https: https://submit.mis.s-3.net/ Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.