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

Primary Purpose

HIV, Cardiovascular Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Canakinumab

Placebo

About this trial

This is an interventional treatment trial for HIV

Eligibility Criteria

40 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

HIV infection,
Age ≥ 40 years < 60 years
On continuous ART for at least 12 months with no change in regimen in 12 weeks prior to study entry
CD4+ T cell count ≥ 400 cells/mm3
HIV RNA level below the standard limit of quantification for 52 weeks prior to entry
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.)
Individuals on stable doses of lipid lowering therapy and/or anti-hypertensive medication will be allowed in the study.
Appropriate documentation from medical records of prior receipt of pneumococcal vaccinations

Exclusion Criteria:

Women of childbearing potential or pregnant/nursing women
CABG surgery in the past 3 years
Class IV heart failure
Uncontrolled HTN
History of tuberculosis or latent TB that is not treated
Nephrotic syndrome or eGFR< 30 ml/min/1.73m2
Active hepatic disease or active/chronic hepatitis B or C
Any prior malignancy including KS
Serious illness requiring hospitalization or active infection requiring antibiotics within 90 days
Requirement for live active vaccination 3 months prior to, during, and 3 months after study
Concurrent immune modulating therapy
Diabetes Mellitus
History of multiple imaging studies associated with radiation exposure
Neutropenia defined as ANC<1500/mm
Triglycerides>400 mg/dL
History of hypersensitivity to study drug
History of EBV-related lymphoproliferative disorders
Active or untreated latent TB infection

Sites / Locations

San Francisco General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Experimental

Placebo Comparator

Arm Label

Safety Arm

Canakinumab

Placebo

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Change in CD4 Count From Baseline to Follow-up

Change in CD4 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.

Change in CD8 Count From Baseline to Follow-up

Change in CD8 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.

Change in Absolute Neutrophil Count From Baseline to Follow-up

Change in absolute neutrophil count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.

Change in Platelet Count From Baseline to Follow-up

Change in platelet count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.

Change in Creatinine Count From Baseline to Follow-up

Change in creatinine count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.

Change in AST From Baseline to Follow-up

Change in AST from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.

Change in ALT From Baseline to Follow-up

Change in ALT from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.

Secondary Outcome Measures

Flow-Mediated Dilation (FMD)

Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter

Arterial Inflammation Measured at Baseline and Follow-up at Week 12

Change From Baseline in Arterial Fluorodeoxyglucose (FDG) Uptake Assessed by FDG-PET/CT and reported as target-to-background (TBR) ratio to measure of vascular inflammation

D-Dimer

D-Dimer will be assessed from baseline to weeks 4, 8, 12, and 18.

Human Serum Amyloid A (SAA)

SAA will be assessed from baseline to weeks 4, 12, and 18.

Tumor Necrosis Factor Alpha (TNFa)

TNFa will be assessed from baseline to weeks 4, 12, and 18.

Full Information

NCT ID

NCT02272946

First Posted

October 13, 2014

Last Updated

March 29, 2023

Sponsor

Priscilla Hsue, MD

Collaborators

Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02272946

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

September 2015 (undefined)

Primary Completion Date

February 2021 (Actual)

Study Completion Date

December 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Priscilla Hsue, MD

Collaborators

Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV, Cardiovascular Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

43 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Safety Arm

Arm Type

Other

Arm Description

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

Arm Title

Canakinumab

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Canakinumab

Other Intervention Name(s)

IL--1β

Intervention Description

150mg Canakinumab received subcutaneously

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

150mg Placebo received subcutaneously

Primary Outcome Measure Information:

Title

Change in CD4 Count From Baseline to Follow-up

Description

Change in CD4 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.

Time Frame