Immunomodulation Using VB-201 to Reduce Arterial Inflammation in Treated HIV - VITAL HIV Trial

Study Overview
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Brief Summary
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This study is a double blinded, placebo-controlled, randomized, parallel group study, designed to compare the efficacy and safety of VB-201 80mg taken orally once daily to placebo for anti-inflammation in HIV-infected subjects.

Official Title
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Immunomodulation Using VB-201 to Reduce Arterial Inflammation in Treated HIV - VITAL HIV Trial

Conditions
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Inflammation, HIV Infection, Cardiovascular Disease

Intervention / Treatment
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* Drug: VB-201
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 > 350 cells/mm3 Male or female between the ages ≥ 40 years of age to <≤75 Documented cardiovascular disease (1. Prior myocardial infarction, 2. History of percutaneous coronary intervention, 3. History of coronary artery bypass graft OR 4. 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 as defined by menopause with amenorrhea for >2 years, bilateral oophorectomy, or agree to use adequate contraception throughout the study and for at least one month following termination and have a negative pregnancy test at screening prior to the first dose of drug. Males must use at least one method of contraception throughout the study. Exclusion Criteria: Pregnant/nursing women Uncontrolled hypertension or diabetes requiring insulin AST/ALT or alkaline phosphatase >2x ULN Cancer within the last 5 years with exception of squamous cell carcinoma and basal cell carcinoma Nephrotic syndrome or eGFR <60 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 <10 g/dL Evidence of tuberculosis infection at screening within 30 days prior to screening. Family history of long QT syndrome, using medication that prolongs QT internal, OR evidence of prolonged QT of >470 msec as evidenced by ECG Acute systemic infection within 30 days On additional immunosuppressant or immunomodulatory therapies

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VB-201<br>One dose of VB-201 80 mg (1 tablet) will be administered orally once daily for 52 weeks. | Drug: VB-201<br>* One dose of VB-201 80 mg (1 tablet) will be administered orally once daily for 52 weeks.<br>|
| Placebo Comparator: Placebo<br>One dose of placebo 80 mg (1 tablet) will be administered orally once daily for 52 weeks. | Drug: Placebo<br>* One dose of placebo 80 mg (1 tablet) will be administered orally once daily for 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Target-to-background ratio (TBR) | Change in Target-to-background ratio (TBR) from baseline to follow-up study at 52 weeks as assessed by Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) | 1 year (Baseline and Week 52) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in high sensitivity C-reactive protein (hs-CRP) in mg/L | Change in hs-CRP from baseline to week 24 and baseline to week 52 as measured by blood collection | 1 year (Change from baseline to week 24 and baseline to week 52) | 
| Change in Interleukin-6 (IL-6) in pg/mL | Change in IL-6 from baseline to week 24 and baseline to week 52 as measured by blood collection | 1 year (Change from baseline to week 24 and baseline to week 52) | 
| Change in soluble cluster of differentiation (sCD163) ng/mL | Change in sCD163 from baseline to week 24 and baseline to week 52 as measured by blood collection | 1 year (Change from baseline to week 24 and baseline to week 52) | 
| Change in Lipoprotein (a) [Lp(a)] in mg/dL | Change in Lp(a) from baseline to week 24 and baseline to week 52 as measured by blood collection | 1 year (Change from baseline to week 24 and baseline to week 52) | 
| Change in Lipoprotein-associated Phospholipase A2 (Lp-PLA2) in ng/mL | Change in Lp-PLA2 from baseline to week 24 and baseline to week 52 as measured by blood collection | 1 year (Change from baseline to week 24 and baseline to week 52) | 
| Change in D-Dimer (ng/mL) | Change in D-Dimer from baseline to week 24 and baseline to week 52 as measured by blood collection | 1 year (Change from baseline to week 24 and baseline to week 52) | 
| Change in Markers of Immune Activation | Change in Co-expression of HLA-DR/CD38 on T-cells from baseline to week 24 and baseline to week 52 as measured by blood collection | 1 year (Change from baseline to week 24 and baseline to week 52) | 
| Change in Monocyte Activation | Change in Co-expression of CD14/CD16 on Monocytes from baseline to week 24 and baseline to week 52 | 1 year (Change from baseline to week 24 and baseline to week 52) |