Human Immunodeficiency VirusPhase 2EVOLVENCT03500302
Effect of Evolocumab on Coronary Endothelial Function
A Phase 2 study testing Evolocumab in people with Human Immunodeficiency Virus and Coronary Artery Disease, run by Johns Hopkins University at 1 site in United States.
Trial summary
The investigators propose a pilot study using (1) MRI to assess coronary artery endothelial function, (2) brachial ultrasound to assess systemic endothelial function, (3) serum markers of inflammation and of endothelial cell function and (4) echocardiographic measures of left ventricular diastolic and systolic… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Human Immunodeficiency Virus, Coronary Artery Disease
- What is being tested?
- Evolocumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 4 May 2018to 30 Nov 2019
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants of either gender who are >21 years of age (no upper age limit)
- HIV (Human Immunodeficiency Virus) positive and taking stable Anti-Retroviral Therapy (ART), no change in regimen in last 3 months)
- Undetectable HIV viral load (plasma HIV RNA concentration, RNA=Ribonucleic Adic)
- Abnormal coronary endothelial function on MRI (Magnetic Resonance Imaging) at baseline (<5% change in coronary cross sectional area during isometric handgrip exercise as compared to resting value).
- Lipids at screening visit: Fasting LDL-C >70 mg/dL (LDL-C=Low Density Lipoprotein Cholesterol); fasting TG<500 mg/dL (TG=Triglycerides)
- Permission of treating physician
Who cannot join
- Patients unable to understand the risks, benefits, and alternatives of participation and give meaningful consent.
- Patients with contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips),
- History of a recent cardiovascular or cerebrovascular events or procedure (e.g. myocardial infarction, stroke, transient ischemic attack, angioplasty, Coronary artery bypass surgery) during the past 90 days.
- Subjects with prior exposure to evolocumab or another PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitor.
- Pregnant women or breastfeeding women. Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed.
- 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 recreational drugs within 6 months prior to screening.
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- Renal impairment defined by estimated glomerular filtration rate <45 ml/min.
- Moderate-severe hepatic disease (elevation in hepatic transaminases >3x upper limit of normal, ULN) or direct bilirubin >3.0 X ULN at screening.
- Cluster of differentiation 4 (CD4)<200 cell/mm3
- Congestive heart failure, New York Heart Association functional class III or greater, or left ventricular ejection fraction measured by imaging known to be <30%. (Imaging not required for study inclusion).
- History of allergic or anaphylactic reaction to any therapeutic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibodies
- Active phase hepatitis. Stable patients with hepatitis B or C infection >3 years before randomization are eligible.
Trial locations and contacts
1 site in 1 country.
About this study
The investigators propose a pilot study using (1) MRI to assess coronary artery endothelial function, (2) brachial ultrasound to assess systemic endothelial function, (3) serum markers of inflammation and of endothelial cell function and (4) echocardiographic measures of left ventricular diastolic and systolic properties, before and following initiation of PCSK9 antibody in HIV positive subjects.
Read the detailed description
To evaluate the effect of the PCSK9 inhibitor evolocumab on coronary and systemic endothelial function, systemic biomarkers of endothelial function and of inflammation, and echocardiographic measures of left ventricular diastolic and systolic properties in subjects who are HIV+. Potential participants will be asked to undergo a screening MRI exam. Those who have evidence of coronary endothelial dysfunction on the MRI exam will receive evolocumab 420 mg sq (the dose that is approved for treatment of hypercholesterolemia) following the screening exam and again at one month. Repeat MRI and ultrasound measures of coronary and systemic endothelial function, as well as serum markers of endothelial function and inflammation, and echocardiographic measures of diastolic and systolic left ventricular function will be obtained at one and six weeks following the first administration of evolocumab.
The investigators will test the hypotheses that PCSK9 inhibition improves endothelial function measured non-invasively on MRI and systemic markers of inflammation at one week (+/- 3 days) and six weeks after initiation of the PCSK9 antibody.
- Being tested
- Evolocumab
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabDrug
Also called Repatha
Evolocumab sq once a month for a total of two doses
| Study group | Role | What they receive |
|---|---|---|
| Evolocumab | Experimental | All enrolled patients will receive evolocumab sq once a month for a total of two doses Receives: Drug: Evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Coronary Endothelial Function as Assessed by Percent Coronary Artery Area Change With Isometric Handgrip Exercise
Coronary endothelial function will be assessed by the percent change in cross sectional coronary artery area (measured on MRI) from rest to isometric handgrip stress exercise at week 1 and week 6. The percent change from week 1 to week 6 is presented below.
Measured: 1 week and 6 weeks
Secondary outcomes (1)
LDL Cholesterol Level
LDL cholesterol level: mg/dL.
Measured: At 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2018
- Study start4 May 2018
- Primary completion30 Nov 2019
- Study completion30 Nov 2019
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 Human Immunodeficiency VirusStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- Pilot clinical trial to study HIV+ patients with baseline coronary endothelial dysfunction and assess changes in that function from the baseline measure to 1 and 6 weeks following initiation of therapy with evolocumab so as to test the hypotheses that PCSK9 inhibition with evolocumab improves coronary endothelial function (CEF) measured directly and non-invasively with MRI at 1 week and 6 weeks after initiation of evolocumab.
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Sponsor
- Investigators
- Allison Hays, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03500302
- Sponsor's protocol ID
- IRB00127952
- Acronym
- EVOLVE
- Status last verified
- Jul 2020
- First submitted
- 27 Nov 2017
- Last updated
- 24 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Leucker TM, Gerstenblith G, Schar M, Brown TT, Jones SR, Afework Y, Weiss RG, Hays AG. Evolocumab, a PCSK9-Monoclonal Antibody, Rapidly Reverses Coronary Artery Endothelial Dysfunction in People Living With HIV and People With Dyslipidemia. J Am Heart Assoc. 2020 Jul 21;9(14):e016263. doi: 10.1161/JAHA.120.016263. Epub 2020 Jul 17.
PubMed 32674634
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Evolocumab on Coronary Endothelial Function
- ClinicalTrials.gov ID
- NCT03500302
- Acronym / sponsor ID
- EVOLVE / IRB00127952
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- 4 May 2018 (actual)
- Primary completion
- 30 Nov 2019 (actual)
- Study completion
- 30 Nov 2019 (actual)
- First posted
- 18 Apr 2018 (actual)
- Results
- Posted 24 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose a pilot study using (1) MRI to assess coronary artery endothelial function, (2) brachial ultrasound to assess systemic endothelial function, (3) serum markers of inflammation and of endothelial cell function and (4) echocardiographic measures of left ventricular diastolic and systolic properties, before and following initiation of PCSK9 antibody in HIV positive subjects.
Detailed description
To evaluate the effect of the PCSK9 inhibitor evolocumab on coronary and systemic endothelial function, systemic biomarkers of endothelial function and of inflammation, and echocardiographic measures of left ventricular diastolic and systolic properties in subjects who are HIV+. Potential participants will be asked to undergo a screening MRI exam. Those who have evidence of coronary endothelial dysfunction on the MRI exam will receive evolocumab 420 mg sq (the dose that is approved for treatment of hypercholesterolemia) following the screening exam and again at one month. Repeat MRI and ultrasound measures of coronary and systemic endothelial function, as well as serum markers of endothelial function and inflammation, and echocardiographic measures of diastolic and systolic left ventricular function will be obtained at one and six weeks following the first administration of evolocumab.
The investigators will test the hypotheses that PCSK9 inhibition improves endothelial function measured non-invasively on MRI and systemic markers of inflammation at one week (+/- 3 days) and six weeks after initiation of the PCSK9 antibody.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Pilot clinical trial to study HIV+ patients with baseline coronary endothelial dysfunction and assess changes in that function from the baseline measure to 1 and 6 weeks following initiation of therapy with evolocumab so as to test the hypotheses that PCSK9 inhibition with evolocumab improves coronary endothelial function (CEF) measured directly and non-invasively with MRI at 1 week and 6 weeks after initiation of evolocumab.
| Arm | Type | Receives |
|---|---|---|
| Evolocumab | Experimental | Drug: EvolocumabAll enrolled patients will receive evolocumab sq once a month for a total of two doses |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participants of either gender who are >21 years of age (no upper age limit)
- HIV (Human Immunodeficiency Virus) positive and taking stable Anti-Retroviral Therapy (ART), no change in regimen in last 3 months)
- Undetectable HIV viral load (plasma HIV RNA concentration, RNA=Ribonucleic Adic)
- Abnormal coronary endothelial function on MRI (Magnetic Resonance Imaging) at baseline (<5% change in coronary cross sectional area during isometric handgrip exercise as compared to resting value).
- Lipids at screening visit: Fasting LDL-C >70 mg/dL (LDL-C=Low Density Lipoprotein Cholesterol); fasting TG<500 mg/dL (TG=Triglycerides)
Key exclusion criteria (12 listed)
- Patients unable to understand the risks, benefits, and alternatives of participation and give meaningful consent.
- Patients with contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips),
- History of a recent cardiovascular or cerebrovascular events or procedure (e.g. myocardial infarction, stroke, transient ischemic attack, angioplasty, Coronary artery bypass surgery) during the past 90 days.
- Subjects with prior exposure to evolocumab or another PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitor.
- Pregnant women or breastfeeding women. Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed.
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 |
|---|---|---|
| EvolocumabAlso: RepathaEvolocumab sq once a month for a total of two doses | Drug | Evolocumab |
Primary outcome
Coronary Endothelial Function as Assessed by Percent Coronary Artery Area Change With Isometric Handgrip Exercise
Time frame: 1 week and 6 weeks
Coronary endothelial function will be assessed by the percent change in cross sectional coronary artery area (measured on MRI) from rest to isometric handgrip stress exercise at week 1 and week 6. The percent change from week 1 to week 6 is presented below.
1 secondary outcome
LDL Cholesterol Level
Time frame: At 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32674634Leucker TM, Gerstenblith G, Schar M, Brown TT, Jones SR, Afework Y, Weiss RG, Hays AG. Evolocumab, a PCSK9-Monoclonal Antibody, Rapidly Reverses Coronary Artery Endothelial Dysfunction in People Living With HIV and People With Dyslipidemia. J Am Heart Assoc. 2020 Jul 21;9(14):e016263. doi: 10.1161/JAHA.120.016263. Epub 2020 Jul 17.
- Individual participant dataSharing planned: No
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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.
Allison Hays, MD principal investigator
Johns Hopkins University
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 Evolocumab in people with Human Immunodeficiency Virus and Coronary Artery Disease, run by Johns Hopkins University 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 6 inclusion and 12 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 24 Jul 2020. 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. 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 24 Jul 2020). 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?
Coronary Endothelial Function as Assessed by Percent Coronary Artery Area Change With Isometric Handgrip Exercise (time frame: 1 week and 6 weeks). 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 NCT03500302, 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 24 Jul 2020.