Clinical trial NCT04939311: Immunomodulation Using VB-201 to Reduce Arterial Inflammation in Treated HIV - VITAL HIV Trial
Official title: Immunomodulation Using VB-201 to Reduce Arterial Inflammation in Treated HIV - VITAL HIV Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Inflammation
HIV Infection
Cardiovascular Disease
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: University of Utah
First posted: 2021-06-25
Enrollment: 0
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Target-to-background ratio (TBR)
timeFrame: 1 year (Baseline and Week 52)
Secondary outcomes:
measure: Change in high sensitivity C-reactive protein (hs-CRP) in mg/L
timeFrame: 1 year (Change from baseline to week 24 and baseline to week 52)
measure: Change in Interleukin-6 (IL-6) in pg/mL
timeFrame: 1 year (Change from baseline to week 24 and baseline to week 52)
measure: Change in soluble cluster of differentiation (sCD163) ng/mL
timeFrame: 1 year (Change from baseline to week 24 and baseline to week 52)
measure: Change in Lipoprotein (a) [Lp(a)] in mg/dL
timeFrame: 1 year (Change from baseline to week 24 and baseline to week 52)
measure: Change in Lipoprotein-associated Phospholipase A2 (Lp-PLA2) in ng/mL
timeFrame: 1 year (Change from baseline to week 24 and baseline to week 52)
measure: Change in D-Dimer (ng/mL)
timeFrame: 1 year (Change from baseline to week 24 and baseline to week 52)
measure: Change in Markers of Immune Activation
timeFrame: 1 year (Change from baseline to week 24 and baseline to week 52)
measure: Change in Monocyte Activation
timeFrame: 1 year (Change from baseline to week 24 and baseline to week 52)
Other outcomes:
measure: Change in non-calcified plaque progression
timeFrame: 1 year (Baseline and Week 52)
measure: Change in high risk plaque
timeFrame: 1 year (Baseline and Week 52)
measure: Incidence of new lesions
timeFrame: 1 year (Baseline and Week 52)
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Priscilla Hsue, MD
role: PRINCIPAL_INVESTIGATOR
References: