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

NCT02272946 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Canakinumab
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  weeks 4, 8, 12, 18, 24, and 36.

Secondary Outcomes (5)

• Flow-Mediated Dilation (FMD)

  Baseline and Week 12

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

  Baseline (entry) and Week 12

• D-Dimer

  Baseline, 4 weeks, 8 weeks, 12 weeks, and week 18

• Human Serum Amyloid A (SAA)

  Baseline, 4 weeks, 12 weeks, and week 18

• Tumor Necrosis Factor Alpha (TNFa)

  Baseline, 4 weeks, 12 weeks, and week 18

Study Arms (3)

Safety Arm

OTHER

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

Drug: Canakinumab

Canakinumab

EXPERIMENTAL

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

Drug: Canakinumab

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Canakinumab DRUG

150mg Canakinumab received subcutaneously

Also known as: IL--1β

Canakinumab; Safety Arm

Placebo DRUG

150mg Placebo received subcutaneously

Placebo

Eligibility Criteria

• Age: 40 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Priscilla Hsue, MD: lead
• Massachusetts General Hospital: collaborator

Study Sites (1)

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Related Publications (1)

• 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.

  PMID: 35938460 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

canakinumab

Results Point of Contact

• Title: Priscilla Hsue, MD
• Organization: University of California, San Francisco

Priscilla.hsue@ucsf.edu

628-206-5801

Study Officials

• Priscilla Hsue, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 13, 2014
• First Posted: October 23, 2014
• Study Start: September 1, 2015
• Primary Completion: February 1, 2021
• Study Completion: December 1, 2021
• Last Updated: April 20, 2023
• Results First Posted: April 20, 2023

Record last verified: 2023-03

Locations

US (1)