HIVPhase 2NCT02272946

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

A Phase 2 study testing Canakinumab in people with HIV and Cardiovascular Disease, run by Priscilla Hsue, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 to 59 years
Conditions the study is for: HIV, Cardiovascular Disease
What is being tested?: Canakinumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 43 participants
Where: 1 siteUnited States
Study dates: Sep 2015to Dec 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 59 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

Who cannot join

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

Show all 18Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

San Francisco General Hospital
San Francisco, California, 94110

Other trials in United States

About this study

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
Being tested: Canakinumab, Placebo
Medical subject headings: Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CanakinumabDrug
Also called IL--1β
150mg Canakinumab received subcutaneously
PlaceboDrug
150mg Placebo received subcutaneously

Study groups in NCT02272946
Study group	Role	What they receive
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). Receives: Drug: Canakinumab
Canakinumab	Experimental	In Stage II: About 67 subjects will receive 150mg Canakinumab subcutaneous injection. Receives: Drug: Canakinumab
Placebo	Placebo comparator	In Stage II: About 33 subjects will receive 150mg placebo subcutaneous injection Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (5)

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
Measured: Baseline and Week 12
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
Measured: Baseline (entry) and Week 12
D-Dimer
D-Dimer will be assessed from baseline to weeks 4, 8, 12, and 18.
Measured: Baseline, 4 weeks, 8 weeks, 12 weeks, and week 18
Human Serum Amyloid A (SAA)
SAA will be assessed from baseline to weeks 4, 12, and 18.
Measured: Baseline, 4 weeks, 12 weeks, and week 18
Tumor Necrosis Factor Alpha (TNFa)
TNFa will be assessed from baseline to weeks 4, 12, and 18.
Measured: Baseline, 4 weeks, 12 weeks, and week 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2015Dec 2021

First posted23 Oct 2014 (estimated)
Study startSep 2015
Primary completionFeb 2021
Study completionDec 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIVStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02272946
Sponsor's protocol ID: Canakinumab
Status last verified: Mar 2023
First submitted: 13 Oct 2014
Last updated: 20 Apr 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 35938460

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 20 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
ClinicalTrials.gov ID: NCT02272946
Acronym / sponsor ID: Canakinumab
Conditions: HIV, Cardiovascular Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 43 participants (actual)
Lead sponsor: Priscilla Hsue, MDUniversity, hospital or other
Collaborators: Massachusetts General Hospital
Study start: Sep 2015
Primary completion: Feb 2021 (actual)
Study completion: Dec 2021 (actual)
First posted: 23 Oct 2014 (estimated)
Results: Posted 20 Apr 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Safety Arm	Other	Drug: CanakinumabIn Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab	Experimental	Drug: CanakinumabIn Stage II: About 67 subjects will receive 150mg Canakinumab subcutaneous injection.
Placebo	Placebo comparator	Drug: PlaceboIn Stage II: About 33 subjects will receive 150mg placebo subcutaneous injection

Who may qualify

Ages: 40 to 59 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (18 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CanakinumabAlso: IL--1β150mg Canakinumab received subcutaneously	Drug	Canakinumab, Safety Arm
Placebo150mg Placebo received subcutaneously	Drug	Placebo

Primary outcome

Change in CD4 Count From Baseline to Follow-up
Time frame: weeks 4, 8, 12, 18, 24, and 36.
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
Time frame: weeks 4, 8, 12, 18, 24, and 36.
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
Time frame: weeks 4, 8, 12, 18, 24, and 36.
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
Time frame: weeks 4, 8, 12, 18, 24, and 36.
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
Time frame: weeks 4, 8, 12, 18, 24, and 36.
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
Time frame: weeks 4, 8, 12, 18, 24, and 36.
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
Time frame: weeks 4, 8, 12, 18, 24, and 36.
Change in ALT from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.

5 secondary outcomes

Flow-Mediated Dilation (FMD)
Time frame: Baseline and Week 12
Arterial Inflammation Measured at Baseline and Follow-up at Week 12
Time frame: Baseline (entry) and Week 12
D-Dimer
Time frame: Baseline, 4 weeks, 8 weeks, 12 weeks, and week 18
Human Serum Amyloid A (SAA)
Time frame: Baseline, 4 weeks, 12 weeks, and week 18
Tumor Necrosis Factor Alpha (TNFa)
Time frame: Baseline, 4 weeks, 12 weeks, and week 18

Results and safety

Results posted to the registry on 20 Apr 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Safety Arm	10	10
Canakinumab	25	25
Placebo	8	8

Primary outcome: Change in CD4 Count From Baseline to Follow-up

Time frame: weeks 4, 8, 12, 18, 24, and 36.. Median (Inter-Quartile Range). Unit: log cells per mm^3

Measure	Safety Arm n = 10	Canakinumab n = 25	Placebo n = 8
Week 4	-0.085 (-0.170 to 0.008)	-0.024 (-0.106 to 0.065)	-0.020 (-0.149 to 0.129)
Week 8	-0.090 (-0.174 to 0.003)	0.004 (-0.084 to 0.100)	-0.015 (-0.145 to 0.134)
Week 12	-0.049 (-0.139 to 0.050)	-0.111 (-0.186 to -0.029)	-0.070 (-0.192 to 0.072)
Week 18	–	-0.105 (-0.182 to -0.020)	-0.009 (-0.140 to 0.142)
Week 24	–	-0.142 (-0.220 to -0.057)	-0.012 (-0.147 to 0.145)
Week 36	–	-0.109 (-0.189 to -0.020)	-0.164 (-0.278 to -0.032)

Population analysed: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.

Primary outcome: Change in CD8 Count From Baseline to Follow-up

Time frame: weeks 4, 8, 12, 18, 24, and 36.. Median (Inter-Quartile Range). Unit: log cells per mm^3

Measure	Safety Arm n = 10	Canakinumab n = 25	Placebo n = 8
Week 4	-0.101 (-0.257 to 0.088)	-0.039 (-0.125 to 0.050)	0.006 (-0.133 to 0.168)
Week 8	-0.103 (-0.259 to 0.086)	-0.069 (-0.154 to 0.030)	-0.040 (-0.173 to 0.115)
Week 12	-0.166 (-0.313 to 0.014)	-0.192 (-0.264 to -0.110)	-0.111 (-0.234 to -0.032)
Week 18	–	-0.202 (-0.274 to -0.120)	-0.098 (-0.223 to 0.047)
Week 24	–	-0.159 (-0.239 to -0.070)	-0.020 (-0.160 to 0.145)
Week 36	–	-0.171 (-0.250 to -0.080)	-0.198 (-0.313 to -0.063)

Population analysed: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.

Primary outcome: Change in Absolute Neutrophil Count From Baseline to Follow-up

Time frame: weeks 4, 8, 12, 18, 24, and 36.. Median (Inter-Quartile Range). Unit: log unit (k) per uL

Measure	Safety Arm n = 10	Canakinumab n = 25	Placebo n = 8
Week 4	-0.157 (-0.329 to 0.060)	-0.149 (-0.244 to -0.040)	-0.048 (-0.215 to 0.155)
Week 8	-0.137 (-0.314 to 0.084)	-0.015 (-0.130 to 0.120)	0.044 (-0.139 to 0.266)
Week 12	-0.065 (-0.262 to 0.184)	-0.088 (-0.192 to 0.030)	0.046 (-0.137 to 0.269)
Week 18	–	-0.110 (-0.213 to 0.010)	0.053 (-0.131 to 0.278)
Week 24	–	-0.123 (-0.229 to 0.000)	0.028 (-0.159 to 0.256)
Week 36	–	0.056 (-0.072 to 0.200)	0.201 (-0.017 to 0.468)

Population analysed: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.

Primary outcome: Change in Platelet Count From Baseline to Follow-up

Time frame: weeks 4, 8, 12, 18, 24, and 36.. Median (Inter-Quartile Range). Unit: log unit (k) per uL

Measure	Safety Arm n = 10	Canakinumab n = 25	Placebo n = 8
Week 4	-0.098 (-0.168 to -0.022)	-0.079 (-0.131 to -0.020)	0.026 (-0.066 to 0.127)
Week 8	-0.029 (-0.104 to 0.053)	-0.032 (-0.089 to 0.030)	0.007 (-0.083 to 0.107)
Week 12	-0.014 (-0.093 to 0.072)	-0.020 (-0.076 to 0.040)	0.014 (-0.077 to 0.115)
Week 18	–	0.015 (-0.044 to 0.080)	0.028 (-0.065 to 0.129)
Week 24	–	0.016 (-0.046 to 0.080)	0.054 (-0.044 to 0.162)
Week 36	–	0.045 (-0.018 to 0.110)	-0.016 (-0.107 to 0.085)

Population analysed: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 36 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Safety Arm	0 of 10 (0%)	2 of 10 (20%)	0 of 10
Canakinumab	2 of 25 (8%)	1 of 25 (4%)	1 of 25
Placebo	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35938460Kentoffio 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Priscilla Hsue, MD principal investigator

University of California, San Francisco

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Canakinumab in people with HIV and Cardiovascular Disease, run by Priscilla Hsue, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in CD4 Count From Baseline to Follow-up (time frame: weeks 4, 8, 12, 18, 24, and 36.). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02272946, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2023.