Clinical trial NCT04425733: Frespaciguat (MK-5475) in Participants With Hypoxemia Due to COVID-19 Pneumonia (MK-5475-009)
Official title: A Study to Assess the Safety, Tolerability, and Pharmacodynamics of Multiple Dose MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Coronavirus Disease 2019 (COVID-19)
Pneumonia
Hypoxemia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-06-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate safety, tolerability, and pharmacodynamics of frespaciguat after administration of multiple doses to participants with COVID-19 pneumonia. The primary hypothesis is that frespaciguat when administered to participants with COVID-19 pneumonia and hypoxemia improves arterial oxygenation as measured by the ratio of blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 ratio) compared to placebo.


Eligibility criteria: Inclusion Criteria:

* Has virologically confirmed COVID-19 requiring hospital admission.
* Has respiratory symptoms including cough and dyspnea
* Requires supplemental oxygen therapy
* Male participant is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 14 days, corresponding to time needed to eliminate study intervention(s) (example, 5 terminal half-lives after the last dose of study intervention)
* Female participant is not a woman of childbearing potential (WOCBP) or is a WOCBP who is abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 14 days, corresponding to time needed to eliminate study intervention(s) (example, 5 terminal half-lives after the last dose of study intervention)

Exclusion Criteria:

* Has pre-existing medical conditions of any nature which are immediately pre-terminal such as death or limitation of life-sustaining therapy is expected to be imminent
* Requires or is expected to require invasive mechanical ventilation
* Requires or is expected to require noninvasive mechanical ventilation
* Has any issue which would prohibit them from effective use of the frespaciguat inhaler
* Hypoxemia which is explained by any condition other than COVID-19, example, preexisting cardiac or pulmonary disease
* Has severe hepatic impairment (meets Child-Pugh Class C criteria)
* Has severe renal impairment and/or requirement for renal dialysis

Primary outcomes:
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to ~Day 21
measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
timeFrame: Up to ~Day 7
measure: Change From Baseline to Day 1 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)
timeFrame: Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
measure: Change From Baseline to Day 2 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)
timeFrame: Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
measure: Change From Baseline to Day 3 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)
timeFrame: Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
measure: Change From Baseline to Day 4 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)
timeFrame: Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
measure: Change From Baseline to Day 5 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)
timeFrame: Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
measure: Change From Baseline to Day 6 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)
timeFrame: Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
measure: Change From Baseline to Day 7 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)
timeFrame: Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: