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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05488431




Registration number
NCT05488431
Ethics application status
Date submitted
25/07/2022
Date registered
4/08/2022
Date last updated
3/07/2023

Titles & IDs
Public title
Cholesterol and Inflammation Lowering Via Bempedoic Acid, an ACL-inhibiting Regimen in HIV Trial (CLEAR HIV Trial)
Scientific title
Cholesterol and Inflammation Lowering Via Bempedoic Acid, an ACL-inhibiting Regimen in HIV Trial (CLEAR HIV Trial)
Secondary ID [1] 0 0
1.0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bempedoic acid
Other interventions - Placebo

Experimental: Bempedoic acid (BA) - Patients randomized into the BA arm will receive 180 mg BA administered orally once daily without food for 52 weeks.

Placebo Comparator: Placebo - Patients randomized into the placebo arm will receive 180 mg placebo administered orally once daily without food for 52 weeks.


Treatment: Drugs: Bempedoic acid
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 interventions: Placebo
Placebo

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
FDG PET/CT Endpoint
Timepoint [1] 0 0
Baseline and Week 52
Secondary outcome [1] 0 0
Total Cholesterol Endpoint
Timepoint [1] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [2] 0 0
HDL Endpoint
Timepoint [2] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [3] 0 0
LDL Endpoint
Timepoint [3] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [4] 0 0
Triglycerides Endpoint
Timepoint [4] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [5] 0 0
Apolipoprotein B Endpoint
Timepoint [5] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [6] 0 0
Hb A1c Endpoint
Timepoint [6] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [7] 0 0
Fasting glucose Endpoint
Timepoint [7] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [8] 0 0
Insulin Endpoint
Timepoint [8] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [9] 0 0
homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Endpoints
Timepoint [9] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [10] 0 0
Adipose Volume Endpoint
Timepoint [10] 0 0
Baseline and Week 52
Secondary outcome [11] 0 0
hsCRP Endpoint
Timepoint [11] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [12] 0 0
IL-1B Endpoint
Timepoint [12] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [13] 0 0
IL-18 Endpoint
Timepoint [13] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [14] 0 0
SAA Endpoint
Timepoint [14] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [15] 0 0
Lp-PLA2 Endpoint
Timepoint [15] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [16] 0 0
sCD163 Endpoint
Timepoint [16] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [17] 0 0
IL-6 Endpoint
Timepoint [17] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [18] 0 0
D-Dimer Endpoint
Timepoint [18] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [19] 0 0
Fibrinogen Endpoint
Timepoint [19] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [20] 0 0
T-cell Endpoint
Timepoint [20] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [21] 0 0
B-cell Endpoint
Timepoint [21] 0 0
Baseline, Week 24 and Week 52
Secondary outcome [22] 0 0
Monocyte activation Endpoint
Timepoint [22] 0 0
Baseline, Week 24 and Week 52

Eligibility
Key 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.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California

Funding & Sponsors
Primary sponsor type
Other
Name
Priscilla Hsue, MD
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Priscilla Hsue, MD
Address 0 0
University of California, San Francisco
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Marta Levkova
Address 0 0
Country 0 0
Phone 0 0
628-206-8037
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.