Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19

A Randomized, Double-blind, Dose-ranging, Placebo Controlled, Phase 2a Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19 (INTEGRIS-ARDS)

Evaluation of the safety, tolerability, and pharmacokinetics of PLN-74809 in participants with acute respiratory distress syndrome (ARDS) associated with at least severe COVID-19

Approximately 36 participants will be enrolled sequentially into 3 cohorts. Within each cohort of 12 participants, 9 will be randomized to PLN-74809 and 3 will be randomized to placebo (3:1 ratio).

• In Part 1, approximately 12 participants will be randomized to Dose level 1 of PLN-74809 or placebo QD
• In Part 2, approximately 12 participants will be randomized to Dose level 2 of PLN-74809 or placebo QD
• In Part 3, approximately 12 participants will be randomized to Dose level 3 of PLN-74809 or placebo QD

Inclusion Criteria:

• Diagnosis of ARDS (Berlin Criteria)
• Hospitalized with at least severe COVID-19 (FDA 2020)
• Receiving support for acute lung injury/respiratory distress via supplemental oxygen
• Serum aspartate aminotransferase (AST) concentration ≤ 120 U/L and serum alanine aminotransferase (ALT) concentration ≤ 150 U/L
• Serum total bilirubin ≤ 1.8 mg/dL, in the absence of Gilbert's syndrome or hemolysis

Exclusion Criteria:

• Greater than 72 hours since time of onset of ARDS.
• Greater than 7 days since start of mechanical ventilation.
• Currently receiving or anticipated to receive extracorporeal life support (ECLS), extracorporeal membrane oxygenation (ECMO) or high-frequency oscillatory ventilation
• Unwillingness to follow lung protective ventilation strategy (i.e., tidal volume of 6 mL/kg of predicted body weight and prone positioning) and fluid management protocol (Fluids and Catheters Treatment Trial [FACTT] Conservative or Lite) per local institutional standards (HFOV).