Acute Respiratory Distress Syndrome, SARS-CoV-2
Conditions
Brief summary
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
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
Interventions
DRUGPLN-74809
PLN-74809
DRUGPlacebo
Placebo
Sponsors
Pliant Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events and Laboratory Abnormalities, Assessed by CTCAE V5.0 | Adverse events were collected from the time the participant signed the Informed Consent Form until the Day 28 study visit | Number of Participants With Treatment-related Adverse Events and Laboratory Abnormalities which was Assessed by CTCAE V5. |
Countries
United States
Participant flow
Recruitment details
The study was discontinued prior to completion of enrollment of Dose 1 due to the lack of participant availability following the introduction of COVID-19 vaccines as well as the increased and successful measures to contain the virus leading to a dramatic decrease in the number of severe and critical COVID-19 patients with ARDS.
Participants by arm
| Arm | Count |
|---|---|
| PLN-74809: Dose 1 (40 mg) N=5 | 5 |
| PLN-74809: Dose 2 (80 mg) not enrolled (study discontinued) | 0 |
| PLN-74809: Dose 3 (160 mg) not enrolled (study discontinued) | 0 |
| Placebo N=1 | 1 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | PLN-74809: Dose 1 (40 mg) |
|---|---|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 0 | 57.5 years STANDARD_DEVIATION 5.86 | 57.4 years STANDARD_DEVIATION 6.54 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 0 | 0 / 0 | 1 / 1 |
| other Total, other adverse events | 5 / 5 | 0 / 0 | 0 / 0 | 1 / 1 |
| serious Total, serious adverse events | 3 / 5 | 0 / 0 | 0 / 0 | 1 / 1 |
Outcome results
Primary
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.
Time frame: Adverse events were collected from the time the participant signed the Informed Consent Form until the Day 28 study visit
Population: 5 Participant received PLN-74809 and 1 participant received Placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PLN-74809: Dose Level 1 (40 mg) | Number of Participants With Treatment-related Adverse Events and Laboratory Abnormalities, Assessed by CTCAE V5.0 | 0 participants |
| Placebo | Number of Participants With Treatment-related Adverse Events and Laboratory Abnormalities, Assessed by CTCAE V5.0 | 0 participants |