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

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.

Study Overview

• Status: Withdrawn
• Conditions: HIV Infection; Inflammation; Cardiovascular Disease
• Intervention / Treatment: Drug: VB-201; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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 > 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in non-calcified plaque progression	Change in non-calcified plaque progression from baseline to week 52 as assessed by Coronary Computed Tomography Angiography (Coronary CTA)	1 year (Baseline and Week 52)
Change in high risk plaque	Change in high-risk plaque from baseline to week 52 as assessed by Coronary Computed Tomography Angiography (Coronary CTA)	1 year (Baseline and Week 52)
Incidence of new lesions	Incidence of new lesions from baseline to week 52 as assessed by Coronary Computed Tomography Angiography (Coronary CTA)	1 year (Baseline and Week 52)

Collaborators and Investigators

• Sponsor: Priscilla Hsue, MD
• Collaborators: University of California, Los Angeles; University of Utah
• Investigators: Principal Investigator: Priscilla Hsue, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): July 1, 2026
• Study Completion (Anticipated): July 1, 2027

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 16, 2021
• First Posted (Actual): June 25, 2021

Study Record Updates

• Last Update Posted (Actual): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Vascular Diseases; Vasculitis; Cardiovascular Diseases; Inflammation; Arteritis
• Other Study ID Numbers: VITAL HIV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No