Effect of PCSK9 Inhibition on Cardiovascular Risk in Treated HIV Infection (EPIC-HIV Study)

NCT03207945 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 17-22800
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

Atherosclerosis in the setting of HIV infection is distinct and includes increased vascular inflammation, worsened endothelial function, and a predominance of non-calcified plaque. These outcomes can be assessed using specialized noninvasive imaging which strongly predict future CV events in the general population. PCSK9 has emerged as an important pharmacologic target for cholesterol lowering in the general population and recent studies among individuals without HIV have shown that PCSK9 inhibitor therapy is safely tolerated and significantly reduces major CV events in the general population. The investigators will perform a clinical trial of PCSK9 inhibition in the setting of HIV infection. This will be a randomized, placebo-controlled study to evaluate the effects of PCSK9 inhibition on vascular inflammation, endothelial function, and non-calcified plaque using a PCSK9 inhibitor called alirocumab. This study will recruit 140 treated individuals with HIV who are aged 40 and older, with known CVD or risk factors for CVD and who have evidence of vascular inflammation at baseline. The primary and secondary objective of this study is to determine whether PCSK9 inhibition can improve arterial inflammation as assessed by FDG-PET/CT and endothelial function as assessed by flow mediated vasodilation. The investigators will correlate changes in arterial inflammation and endothelial function with lipids and markers of inflammation and immune activation. The tertiary objective is to perform a pilot evaluation of the impact of PCSK9 inhibition on non-calcified plaque as measured by coronary CT angiography. Non-calcified plaque measurements will be correlated with changes in lipid parameters and markers of inflammation and immune activation.

Conditions

Dyslipidemias; Cardiovascular Diseases; HIV Infections

Outcome Measures

Primary Outcomes (4)

• FDG PET/CT Endpoint

  Change in Target-to-background ratio from baseline to follow-up study at 52 weeks. The main arterial endpoint is the most diseased segment of the index vessel

  Baseline and Week 52

• FDG PET/CT Endpoint

  Percent change from baseline in fasting TC, HDL-C, triglycerides, non HDL-C, ApoB, ApoA-I at week 24, and 52

  Baseline Week 24, and 52

• FDG PET/CT Endpoint

  Percent change from baseline in fasting oxidized LDL, Lp(a), LpPLA2, sCD14 and T-Cell activation at week 24, and 52

  Baseline, Week 24, and 52

• FDG PET/CT Endpoint

  Correlation of lipid and immune activation parameters to arterial inflammation

  Baseline and Week 52

Secondary Outcomes (6)

• Flow mediated vasodilation of the brachial artery (FMD) endpoint

  Baseline, Week 24 and Week 52

• Flow mediated vasodilation of the brachial artery (FMD) endpoint

  Baseline, Week 24 and Week 52

• Flow mediated vasodilation of the brachial artery (FMD) endpoint

  Baseline, Week 24 and Week 52

• Flow mediated vasodilation of the brachial artery (FMD) endpoint

  Baseline Week 24 and Week 52

• Flow mediated vasodilation of the brachial artery (FMD) endpoint

  Baseline, Week 24 and Week 52

Other Outcomes (7)

• Coronary CTA Endpoint

  Baseline and Week 52

• Coronary CTA Endpoint

  Baseline and Week 52

• Coronary CTA Endpoint

  Baseline and Week 52

Study Arms (2)

Alirocumab

EXPERIMENTAL

Patients randomized into the alirocumab arm will start off with 75 mg alirocumab administered every two weeks for two doses and will be upwardly titrated to 150 mg alirocumab if subjects demonstrate LDL ≥ 50 mg/dL at week 4. Subjects demonstrating LDL-C \<50mg/dl will remain on the same 75mg dose throughout the trial.

Drug: Alirocumab

Placebo

PLACEBO COMPARATOR

Patients randomized into the placebo arm will receive 75 mg or 150 mg or placebo administered once every two weeks throughout the trial

Other: Placebo

Interventions

Alirocumab DRUG

Alirocumab (Sar236553/REG 727) is a fully humanized monoclonal antibody against the proprotein convertase subtilisin kexin type 9 (PCSK9) enzyme responsible for the degradation of the low-density lipoprotein receptor (LDLR), and is developed by Regeneron Pharmaceuticals/Sanofi.

Also known as: Sar236553/REG727

Alirocumab

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Males and females equal or greater than 40 years of age.
• Documented HIV infection.
• HIV-1 RNA level below 200 copies/mL for at least 12 weeks prior to study entry
• CD4 T Cells ≥200 cells/mm3 at screening
• Continuous ART for at least 12 weeks with no change in regimen prior to study entry.
• Moderate or high CVD risk defined as: documented CVD as assessed by meeting at least 1 of 3 criteria below:
• Coronary artery disease (CAD)
• Cerebrovascular disease
• Peripheral arterial disease
• OR any one of the following CVD risk factors:
• Controlled type II diabetes mellitus (HbA1C ≤ 8.0%)
• Family history: a first degree relative who had a heart attack, stroke, or documented CVD as defined in the previous section that occurred: a. When they were age 55 years or younger for males (father, uncle, or brother) b. When they were age 60 years or younger for females (mother, aunt, or sister)
• Current smoking

You may not qualify if:

• Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Regeneron employees.
• Participation in other studies involving small molecule investigational drug(s).
• Subjects who are unable to receive injections, as either a self-injection, or administered by another person.
• Subjects requiring daily insulin therapy
• Intended modification of ART in the next 52 weeks
• History of a cardiovascular or cerebrovascular event or procedure (e.g., myocardial infarction, stroke, transient ischemic attack, angioplasty) during the past 90 days.
• Poorly controlled hypertension
• Any history of hemorrhagic stroke or lacunar infarct.
• Current untreated hypothyroidism or thyroid stimulating hormone (TSH)
• Current history of alcoholism or drug addiction according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria within 12 months prior to screening. Use of any illicit drug confirmed by urine toxicology test at screening that would in the opinion of the investigator interfere with study procedures or results.
• History of cancer within the last 5 years (except for cutaneous basal cell or squamous cell cancer resolved by excision, or cervical carcinoma in situ).
• Any disease or condition that might compromise the hematological, renal, hepatic, pulmonary, endocrine, central nervous, immune, or gastrointestinal systems.
• Undergoing apheresis or have a planned start of apheresis.
• Initiation of or change in non-lipid lowering prescription drugs, herbal medicine or supplements (including foods with added plant sterols and stanols) within 6 weeks of screening with the exception of initiation or change in multivitamins used for general health purposes. Short-term use of medications to treat acute conditions, and vaccines are allowed (e.g., antibiotics or allergy medication).
• History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibodies (e.g., Enbrel® which contains the Fc portion of an antibody or Lucentis® which is a Fab).

Sponsors & Collaborators

• University of California, San Francisco: lead
• Massachusetts General Hospital: collaborator

Study Sites (1)

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Related Publications (1)

• Durstenfeld MS, Levkova-Clark M, Li D, Schaffer V, Abohashem S, Ma Y, Kawai K, Lu MT, Sereti I, Deeks SG, Tawakol A, Hsue PY. Rationale, design, and baseline characteristicss of the effect of PCSK9 inhibition on cardiovascular risk in treated HIV infection: EPIC-HIV randomized clinical trial. Am Heart J. 2026 Feb 28;297:107400. doi: 10.1016/j.ahj.2026.107400. Online ahead of print.

  PMID: 41771366 DERIVED

MeSH Terms

Conditions

Dyslipidemias; Cardiovascular Diseases; HIV Infections

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; 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

• Priscilla Hsue, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 28, 2017
• First Posted: July 5, 2017
• Study Start: April 30, 2018
• Primary Completion: August 24, 2025
• Study Completion: September 24, 2025
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)