Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk

NCT ID: NCT02272946

Last Updated: 2023-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2021-12-31

Brief Summary

The purpose of this study is to evaluate the effects of IL-1β inhibition on safety, measures of systemic and vascular inflammation and endothelial function (all indicators of cardiovascular risk) in treated and suppressed HIV infected individuals This study will assess the safety and effects of canakinumab on endothelial function (assessed by flow-mediated vasodilation [FMD] of the brachial artery), vascular inflammation (assessed by FDG-PET/CT scanning), key inflammatory markers of cardiovascular disease (CVD) risk (high-sensitivity C-reactive protein [hsCRP]), interleukin-6 (IL-6), soluble CD163 (sCD163), D-dimer, T-cell and monocyte activation in the blood, and size of the HIV reservoir. 10 individuals will receive a single dose of 150mg canakinumab with follow-up for 12 weeks. In the second part of the study, 100 participants will be randomized (2:1 - canakinumab to placebo) and will be followed by for 36 weeks.

Conditions

HIV; Cardiovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Safety Arm

In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).

Group Type: OTHER

Canakinumab

Intervention Type: DRUG

150mg Canakinumab received subcutaneously

Canakinumab

In Stage II: About 67 subjects will receive 150mg Canakinumab subcutaneous injection.

Group Type: EXPERIMENTAL

Canakinumab

Intervention Type: DRUG

150mg Canakinumab received subcutaneously

Placebo

In Stage II: About 33 subjects will receive 150mg placebo subcutaneous injection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

150mg Placebo received subcutaneously

Interventions

Canakinumab

150mg Canakinumab received subcutaneously

Intervention Type: DRUG

Placebo

150mg Placebo received subcutaneously

Intervention Type: DRUG

Other Intervention Names

IL--1β

Eligibility Criteria

Inclusion Criteria

1. HIV infection,

2. Age ≥ 40 years < 60 years

3. On continuous ART for at least 12 months with no change in regimen in 12 weeks prior to study entry

4. CD4+ T cell count ≥ 400 cells/mm3

5. HIV RNA level below the standard limit of quantification for 52 weeks prior to entry

6. High risk for CAD as defined by either documented CVD (including prior MI) or diabetes mellitus or 1 CVD risk factor (current smoking, hypertension, dyslipidemia, or hsCRP≥2mg/L.)

7. Individuals on stable doses of lipid lowering therapy and/or anti-hypertensive medication will be allowed in the study.

8. Appropriate documentation from medical records of prior receipt of pneumococcal vaccinations

Exclusion Criteria

1. Women of childbearing potential or pregnant/nursing women

2. CABG surgery in the past 3 years

3. Class IV heart failure

4. Uncontrolled HTN

5. History of tuberculosis or latent TB that is not treated

6. Nephrotic syndrome or eGFR< 30 ml/min/1.73m2

7. Active hepatic disease or active/chronic hepatitis B or C

8. Any prior malignancy including KS

9. Serious illness requiring hospitalization or active infection requiring antibiotics within 90 days

10. Requirement for live active vaccination 3 months prior to, during, and 3 months after study

11. Concurrent immune modulating therapy

12. Diabetes Mellitus

13. History of multiple imaging studies associated with radiation exposure

14. Neutropenia defined as ANC<1500/mm

15. Triglycerides>400 mg/dL

16. History of hypersensitivity to study drug

17. History of EBV-related lymphoproliferative disorders

18. Active or untreated latent TB infection

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Priscilla Hsue, MD

OTHER

Sponsor Role: lead

Responsible Party

Priscilla Hsue, MD

Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Priscilla Hsue, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

San Francisco General Hospital

San Francisco, California, United States

Countries

United States

References

Kentoffio K, Temu TM, Shakil SS, Zanni MV, Longenecker CT. Cardiovascular disease risk in women living with HIV. Curr Opin HIV AIDS. 2022 Sep 1;17(5):270-278. doi: 10.1097/COH.0000000000000756. Epub 2022 Jul 5.

Reference Type: DERIVED

PMID: 35938460 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Study Documents

Document Type: Clinical Study Report

The link above shows the current enrollment table of the Canakinumab study as of March 2, 2020.

View Document

Document Type: IL-1B inhibition [by way of Canakinumab] Reduces Atherosclerotic Inflammation in HIV Infection - Journal of the American College of Cardiology

The link above is the research publication written by Dr. Hsue (Primary Investigator) about how IL-1B inhibition \[by way of Canakinumab\] reduces atherosclerotic inflammation in the setting of HIV.

View Document

Other Identifiers

Canakinumab

Identifier Type: -

Identifier Source: org_study_id