- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05488431
Cholesterol and Inflammation Lowering Via Bempedoic Acid, an ACL-inhibiting Regimen in HIV Trial (CLEAR HIV Trial)
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Marta Levkova
- Phone Number: 628-206-8037
- Email: Marta.Levkova@ucsf.edu
Study Locations
-
-
California
-
San Francisco, California, United States, 94110
- Recruiting
- San Francisco General Hospital
-
Principal Investigator:
- Priscilla Hsue, MD
-
Contact:
- Marta Levkova
- Phone Number: 628-206-8037
- Email: Marta.Levkova@ucsf.edu
-
Sub-Investigator:
- Ahmed Tawakol, MD
-
Sub-Investigator:
- Judith Currier, MD
-
Sub-Investigator:
- Adam Spivak, MD
-
Sub-Investigator:
- Steven Deeks, MD
-
Sub-Investigator:
- John Kornak, MD
-
Sub-Investigator:
- Miguel Pampaloni, MD
-
Sub-Investigator:
- Michael Lu, MD
-
Sub-Investigator:
- Yoojin Lee, MD
-
Sub-Investigator:
- Borek Foldyna, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Documented HIV infection
- On continuous antiretroviral therapy and virologically suppressed HIV infection for ≥12 weeks prior to study entry
- CD4 T-cell count ≥ 200 cells/mm3
- Male or female between the ages ≥ 40 years of age
- LDL-C ≥ 70 mg/dL
- Documented cardiovascular disease as defined by: 1. Prior myocardial infarction, 2. Prior cerebrovascular disease, 3. Prior peripheral arterial disease, 4. History of percutaneous coronary intervention, 5. History of coronary artery bypass graft OR 6. Angiographic evidence of >50% stenosis in at least one coronary artery] OR 1 CVD risk factor (T2DM, current smoking, hypertension, dyslipidemia, hsCRP≥2mg/L, family history)
- TBR of >1.6 of the MDS of the carotid/aorta at baseline. This baseline arterial TBR cutoff excludes the rare individual that lacks appreciable arterial inflammation. It is notable that while 5-10% of uninfected individuals will have lower TBRs, it is rare that an HIV infected individual will fall below this range.
- Female subjects must either be of non-childbearing potential (defined as post-menopausal or amenorrhea > 12 months) or agree to use two forms of contraception (one hormonal and one barrier) throughout the study and for at least one month following study completion and have a negative pregnancy test at screening and prior to the first dose of drug.
- Males must use at least one method of contraception throughout the study.
Exclusion Criteria:
- Pregnant/nursing women (as there is no data on bempedoic acid in this setting)
- Diabetes requiring insulin (as insulin treatment alters the uptake of 18FDG)
- Uncontrolled HTN as defined by baseline blood pressure reading of ≥160 mmHg systolic OR ≥100 mmHg diastolic (exclusion criteria in other studies with BA)
- AST/ALT or alkaline phosphatase >2x ULN
- Triglycerides >500 mg/dL at screening
- Cancer within the last 5 years with exception of squamous cell carcinoma and basal cell carcinoma
- Individuals on simvastatin >20mg or pravastatin >40mg. All other dosages and statins will be permitted with close monitoring for myopathies including assessment of CK levels
- Nephrotic syndrome or eGFR <30 mL/min/1.73m2
- Cytopenias which include 1) WBC <3.5 x103/uL 2) Platelet <120 x103/uL 3) ANC <1.5 x103/uL, and absolute lymphocytes <0.8 x 103/uL
- Anemia as fined by Hgb <10 g/dL
- Acute systemic infection within 30 days
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Bempedoic acid (BA)
Patients randomized into the BA arm will receive 180 mg BA administered orally once daily without food for 52 weeks.
|
Bempedoic Acid is an oral first-in-class small molecular adenosine triphosphate (ATP)-citrate lyase (ACL) inhibitor which lowers LDL-C by inhibition of cholesterol synthesis in the liver.
ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway.
Inhibition of ACL by bempedoyl-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of LDL receptors and concomitant suppression of hepatic fatty acid biosynthesis.
BA has been studied in >4300 individuals and is currently being studied in >14,000 individuals in CLEAR Outcomes (NCT02993406).
Other Names:
|
Placebo Comparator: Placebo
Patients randomized into the placebo arm will receive 180 mg placebo administered orally once daily without food for 52 weeks.
|
Placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
FDG PET/CT Endpoint
Time Frame: Baseline and Week 52
|
Change in Target-to-background ratio from baseline to follow-up study at 52 weeks.
The main arterial endpoint is the most diseased segment of the index vessel.
These findings will be correlated to measurements in the secondary endpoint.
|
Baseline and Week 52
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total Cholesterol Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in total cholesterol will be assessed from baseline to week 24 and week 52.
|
Baseline, Week 24 and Week 52
|
HDL Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in HDL will be assessed from baseline to week 24 and week 52.
|
Baseline, Week 24 and Week 52
|
LDL Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in LDL will be assessed from baseline to week 24 and week 52.
|
Baseline, Week 24 and Week 52
|
Triglycerides Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in triglycerides will be assessed from baseline to week 24 and week 52.
|
Baseline, Week 24 and Week 52
|
Apolipoprotein B Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in apolipoprotein B will be assessed from baseline to week 24 and week 52.
|
Baseline, Week 24 and Week 52
|
Hb A1c Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in HbA1c from baseline to week 24 and week 52.
|
Baseline, Week 24 and Week 52
|
Fasting glucose Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in fasting glucose measurements from baseline to week 24 and week 52.
|
Baseline, Week 24 and Week 52
|
Insulin Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in insulin measurements from baseline to week 24 and week 52.
|
Baseline, Week 24 and Week 52
|
homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Endpoints
Time Frame: Baseline, Week 24 and Week 52
|
The change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), a calculation based on insulin and glucose, will also be assessed from baseline to week 24 and 52. The equation simplifies to [HOMA-IR = fasting insulin *fasting glucose /22.5] where fasting plasma insulin is measured in (µIU/mL) and fasting plasma glucose is measured in (mmol/L). Values below 1.0 are generally considered optimal. |
Baseline, Week 24 and Week 52
|
Adipose Volume Endpoint
Time Frame: Baseline and Week 52
|
Change in adipose tissue volumes will be assessed by FDG PET/CT (as measured in primary outcome) from baseline to week 52.
|
Baseline and Week 52
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hsCRP Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in hsCRP from baseline to follow-up at weeks 24 and 52.
|
Baseline, Week 24 and Week 52
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IL-1B Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in IL-1B from baseline to follow-up at weeks 24 and 52.
|
Baseline, Week 24 and Week 52
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IL-18 Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in IL-18 from baseline to follow-up at weeks 24 and 52.
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Baseline, Week 24 and Week 52
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SAA Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in SAA from baseline to follow-up at weeks 24 and 52.
|
Baseline, Week 24 and Week 52
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Lp-PLA2 Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in Lp-PLA2 from baseline to follow-up at weeks 24 and 52.
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Baseline, Week 24 and Week 52
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sCD163 Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in sCD163 from baseline to follow-up at weeks 24 and 52.
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Baseline, Week 24 and Week 52
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IL-6 Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in IL-6 from baseline to follow-up at weeks 24 and 52.
|
Baseline, Week 24 and Week 52
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D-Dimer Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in D-Dimer from baseline to follow-up at weeks 24 and 52.
|
Baseline, Week 24 and Week 52
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Fibrinogen Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in fibrinogen from baseline to follow-up at weeks 24 and 52.
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Baseline, Week 24 and Week 52
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T-cell Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in T-cell marker from baseline to follow up at weeks 24 and 52.
|
Baseline, Week 24 and Week 52
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B-cell Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in B-cell marker from baseline to follow up at weeks 24 and 52.
|
Baseline, Week 24 and Week 52
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Monocyte activation Endpoint
Time Frame: Baseline, Week 24 and Week 52
|
Change in monocyte activation marker from baseline to follow up at weeks 24 and 52.
|
Baseline, Week 24 and Week 52
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Coronary CTA Non-calcified Plaque Endpoint
Time Frame: Baseline and Week 52
|
Change in non-calcified plaque as measured by Coronary CTA from baseline to follow-up study at 52 weeks
|
Baseline and Week 52
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Coronary CTA High-risk Plaque Endpoint
Time Frame: Baseline and Week 52
|
Change in high-risk plaque as measured by Coronary CTA from baseline to follow-up study at 52 weeks.
|
Baseline and Week 52
|
Coronary CTA Coronary Plaque Incidence Endpoint
Time Frame: Baseline and Week 52
|
Incidence of new coronary lesions as measured by Coronary CTA from baseline to follow-up study at 52 weeks
|
Baseline and Week 52
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Priscilla Hsue, MD, University of California, San Francisco
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Vascular Diseases
- Metabolic Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Lipid Metabolism Disorders
- Cardiovascular Diseases
- Inflammation
- Dyslipidemias
- Atherosclerosis
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Hypolipidemic Agents
- Lipid Regulating Agents
- 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
Other Study ID Numbers
- 1.0
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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