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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2

Conditions: HIV-1-infection; Elevated Cardiovascular Risk

Treatments: Drug: CVC 150 mg; Other: Placebo for CVC 150 mg; Drug: CVC 300 mg; Other: Placebo for CVC 300 mg

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT05630885

A5415

Details and patient eligibility

About

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.

Full 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.

Enrollment: 110 patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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110 participants in 2 patient groups, including a placebo group

CVC arm (Arm A)

Experimental group

Description:

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.

Treatment:

Drug: CVC 300 mg

Drug: CVC 150 mg

Placebo for CVC arm (Arm B)

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo for CVC 300 mg

Other: Placebo for CVC 150 mg