A First-in-Human Study of AV-001 in Healthy Subjects
Condition: Covid19-associated ARDS; Covid19; ARDS
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 1

Summary: 
      Phase 1 randomized, double-blind, placebo-controlled single ascending dose (SAD) and multiple
      ascending dose (MAD) first-in-human study in healthy subjects. Safety and tolerability
      assessments will be conducted, and blood samples will be taken pre-dose and at several time
      points post-dose for pharmacokinetic (PK) and pharmacodynamics (PD) analysis.
    

Detailed description: 
      In the SAD segment of the study, up to 4 ascending cohorts of 8 healthy subjects each will
      receive a single dose of study drug (AV-001 or placebo) in a sequential ascending manner.
      Planned doses may be adapted depending on emergent safety, tolerability and available PK
      data. Screening evaluations will occur from Day -28 to Day -2. Eligible subjects will be
      admitted to the clinical unit on Day -2. On Day 1, subjects will be randomized to AV-001 (6
      subjects) or placebo (2 subjects) and receive a single dose of study drug. Subjects will be
      discharged on Day 2 after all post dose assessments have been completed and if there are no
      medical reasons for a longer stay in the clinical unit. An end of study visit will be
      conducted 7 to 10 days after Day 1 or at early termination.

      An initial sentinel group consisting of 1 subject receiving AV-001 and 1 subject receiving
      placebo will proceed for each cohort prior to treatment of the remainder of the cohort. After
      study drug administration to the sentinel group and an appropriate safety interval (at least
      24 hours and per the discretion of the Principal Investigator (PI)), the remaining 5 subjects
      will receive a single dose of AV-001 and 1 subject will receive placebo administered in the
      same manner.

      PK blood samples will be collected at 15 time points relative to study drug dosing on Day 1.
      PD blood samples for will be collected at 6 time points on Day 1.

      In the MAD segment of the study, up to 2 ascending cohorts of 8 subjects each will receive
      once daily doses of study drug (AV-001 or placebo) for at least 7 days in a sequential
      ascending manner. Planned doses may be adapted and will be determined by the safety,
      tolerability and PK data from the SAD part of the study. Screening evaluations will occur
      from Day -28 to Day -2. Eligible subjects will be admitted to the clinical unit on Day -2. On
      Day 1, subjects will be randomized to AV-001 (6 subjects) or placebo (2 subjects). Subjects
      will receive once-daily doses of study drug from Day 1 through Day 7. Subjects will be
      discharged on Day 8 after all post dose assessments have been completed and if there are no
      medical reasons for a longer stay in the clinical unit. An end of study visit will be
      conducted 7 to 10 days after Day 7 or at early termination.

      PK blood samples will be collected at 15 time points relative to study drug dosing on Day 1
      and Day 7 in addition to predose levels on Days 2 to 6. PD blood samples for will be
      collected at 6 time points on Day 1 and Day 7.
    

Intervention name(s): AV-001; Placebo
Intervention type(s): Drug; Other
Intervention description(s): AV-001 (mpaBr) Cl for Injection 2.5 mg/mL; D-PBS
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Single and multiple ascending dose
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Vascular normalization; Endothelial stability