Immunomodulation Using VB-201 to Reduce Arterial Inflammation in Treated HIV - VITAL HIV Trial
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VB-201 One dose of VB-201 80 mg (1 tablet) will be administered orally once daily for 52 weeks. |
Drug: VB-201
One dose of VB-201 80 mg (1 tablet) will be administered orally once daily for 52 weeks.
|
| Placebo Comparator: Placebo One dose of placebo 80 mg (1 tablet) will be administered orally once daily for 52 weeks. |
Drug: Placebo
One dose of placebo 80 mg (1 tablet) will be administered orally once daily for 52 weeks.
|
Outcome Measures
Primary Outcome Measures
- Change in Target-to-background ratio (TBR) [1 year (Baseline and Week 52)]
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)
Secondary Outcome Measures
- Change in high sensitivity C-reactive protein (hs-CRP) in mg/L [1 year (Change from baseline to week 24 and baseline to week 52)]
Change in hs-CRP from baseline to week 24 and baseline to week 52 as measured by blood collection
- Change in Interleukin-6 (IL-6) in pg/mL [1 year (Change from baseline to week 24 and baseline to week 52)]
Change in IL-6 from baseline to week 24 and baseline to week 52 as measured by blood collection
- Change in soluble cluster of differentiation (sCD163) ng/mL [1 year (Change from baseline to week 24 and baseline to week 52)]
Change in sCD163 from baseline to week 24 and baseline to week 52 as measured by blood collection
- Change in Lipoprotein (a) [Lp(a)] in mg/dL [1 year (Change from baseline to week 24 and baseline to week 52)]
Change in Lp(a) from baseline to week 24 and baseline to week 52 as measured by blood collection
- Change in Lipoprotein-associated Phospholipase A2 (Lp-PLA2) in ng/mL [1 year (Change from baseline to week 24 and baseline to week 52)]
Change in Lp-PLA2 from baseline to week 24 and baseline to week 52 as measured by blood collection
- Change in D-Dimer (ng/mL) [1 year (Change from baseline to week 24 and baseline to week 52)]
Change in D-Dimer from baseline to week 24 and baseline to week 52 as measured by blood collection
- Change in Markers of Immune Activation [1 year (Change from baseline to week 24 and baseline to week 52)]
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
- Change in Monocyte Activation [1 year (Change from baseline to week 24 and baseline to week 52)]
Change in Co-expression of CD14/CD16 on Monocytes from baseline to week 24 and baseline to week 52
Other Outcome Measures
- Change in non-calcified plaque progression [1 year (Baseline and Week 52)]
Change in non-calcified plaque progression from baseline to week 52 as assessed by Coronary Computed Tomography Angiography (Coronary CTA)
- Change in high risk plaque [1 year (Baseline and Week 52)]
Change in high-risk plaque from baseline to week 52 as assessed by Coronary Computed Tomography Angiography (Coronary CTA)
- Incidence of new lesions [1 year (Baseline and Week 52)]
Incidence of new lesions from baseline to week 52 as assessed by Coronary Computed Tomography Angiography (Coronary CTA)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Documented HIV infection
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On continuous antiretroviral therapy and virologically suppressed HIV infection for ≥12 weeks prior to study entry
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CD4 T-cell count > 350 cells/mm3
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Male or female between the ages ≥ 40 years of age to <≤75
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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)
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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.
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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.
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Males must use at least one method of contraception throughout the study.
Exclusion Criteria:
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Pregnant/nursing women
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Uncontrolled hypertension or diabetes requiring insulin
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AST/ALT or alkaline phosphatase >2x ULN
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Cancer within the last 5 years with exception of squamous cell carcinoma and basal cell carcinoma
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Nephrotic syndrome or eGFR <60 mL/min/1.73m2
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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
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Anemia as fined by <10 g/dL
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Evidence of tuberculosis infection at screening within 30 days prior to screening.
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Family history of long QT syndrome, using medication that prolongs QT internal, OR evidence of prolonged QT of >470 msec as evidenced by ECG
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Acute systemic infection within 30 days
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On additional immunosuppressant or immunomodulatory therapies
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Zuckerberg San Francisco General Hospital | San Francisco | California | United States | 94110 |
Sponsors and Collaborators
- Priscilla Hsue, MD
- University of California, Los Angeles
- University of Utah
Investigators
- Principal Investigator: Priscilla Hsue, MD, University of California, San Francisco
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VITAL HIV