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

Study Overview
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Brief Summary
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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

Detailed Description
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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

Official Title
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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)

Conditions
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Acute Respiratory Distress Syndrome, SARS-CoV-2

Intervention / Treatment
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* Drug: PLN-74809
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLN-74809 Dose Level1<br>Dose Level 1 of PLN-74809 | Drug: PLN-74809<br>* PLN-74809<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: PLN-74809 Dose Level 2<br>Dose Level 2 of PLN-74809 | Drug: PLN-74809<br>* PLN-74809<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: PLN74809 Dose Level 3<br>Dose Level 3 of PLN-74809 | Drug: PLN-74809<br>* PLN-74809<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-related Adverse Events and Laboratory Abnormalities, Assessed by CTCAE V5.0 | Number of Participants With Treatment-related Adverse Events and Laboratory Abnormalities which was Assessed by CTCAE V5. | Adverse events were collected from the time the participant signed the Informed Consent Form until the Day 28 study visit |