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

Phase 1

Withdrawn

• Conditions: Inflammation; HIV Infection; Cardiovascular Disease
• Interventions: Drug: Placebo; Drug: VB-201

• Registration Number: NCT04939311
• Lead Sponsor: Priscilla Hsue, MD

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-03
• Study First Submitted QC: 2021-06-16
• Study First Posted: 2021-06-25
• Study Start: 2022-07-01
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-12
• Last Update Posted: 2022-09-15
• Primary Completion: 2026-07-01
• Study Completion: 2027-07-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	One dose of placebo 80 mg (1 tablet) will be administered orally once daily for 52 weeks.
VB-201	VB-201	One dose of VB-201 80 mg (1 tablet) will be administered orally once daily for 52 weeks.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Zuckerberg San Francisco General Hospital; 🇺🇸 San Francisco, California, United States