Frespaciguat (MK-5475) in Participants With Hypoxemia Due to COVID-19 Pneumonia (MK-5475-009)

May 12, 2025 updated by: Merck Sharp & Dohme LLC

A Study to Assess the Safety, Tolerability, and Pharmacodynamics of Multiple Dose MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Panel A Frespaciguat 180 µg
Participants receive 180 µg of frespaciguat once daily (QD) via inhalation from Days 1-7.
Drug: Frespaciguat
Frespaciguat administered at a dose of 180 µg or ≤360 µg QD via inhalation
Other Names:
  • MK-5475
Placebo Comparator: Panel A Placebo
Participants receive frespaciguat-matching placebo QD via inhalation from Days 1-7.
Drug: Placebo
Frespaciguat-matching placebo administered QD via inhalation
Experimental: Panel B Frespaciguat 360 µg
Participants receive 360 µg of frespaciguat QD via inhalation from Days 1-7.
Drug: Frespaciguat
Frespaciguat administered at a dose of 180 µg or ≤360 µg QD via inhalation
Other Names:
  • MK-5475
Placebo Comparator: Panel B Placebo
Participants receive frespaciguat-matching placebo QD via inhalation from Days 1-7.
Drug: Placebo
Frespaciguat-matching placebo administered QD via inhalation
Experimental: Panel C Frespaciguat ≤360 µg
Participants receive ≤360 µg of frespaciguat QD via inhalation from Days 1-7.
Drug: Frespaciguat
Frespaciguat administered at a dose of 180 µg or ≤360 µg QD via inhalation
Other Names:
  • MK-5475
Placebo Comparator: Panel C Placebo
Participants receive frespaciguat-matching placebo QD via inhalation from Days 1-7.
Drug: Placebo
Frespaciguat-matching placebo administered QD via inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experience an Adverse Event (AE)
Time Frame: Up to ~Day 21
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.
Up to ~Day 21
Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
Time Frame: Up to ~Day 7
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study drug due to an AE will be reported.
Up to ~Day 7
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)
Time Frame: Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours post-dose on Day 1 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 1 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 1.
Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
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)
Time Frame: Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 2 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 2 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 2.
Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
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)
Time Frame: Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 3 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 3 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 3.
Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
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)
Time Frame: Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 4 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 4 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 4.
Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
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)
Time Frame: Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 5 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 5 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 5.
Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
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)
Time Frame: Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 6 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 6 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 6.
Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
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)
Time Frame: Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 7 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 7 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 7.
Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 7, 2020

Primary Completion (Estimated)

November 10, 2020

Study Completion (Estimated)

November 10, 2020

Study Registration Dates

First Submitted

June 8, 2020

First Submitted That Met QC Criteria

June 8, 2020

First Posted (Actual)

June 11, 2020

Study Record Updates

Last Update Posted (Actual)

May 15, 2025

Last Update Submitted That Met QC Criteria

May 12, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5475-009
  • 2020-002062-14 (EudraCT Number)
  • MK-5475-009 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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