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

NCT04425733 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: 5475-009MK-5475-0092020-002062-14
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Coronavirus Disease 2019 (COVID-19); Pneumonia; Hypoxemia

Outcome Measures

Primary Outcomes (9)

• Number of Participants Who Experience an Adverse Event (AE)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

Study Arms (6)

Panel A Frespaciguat 180 µg

EXPERIMENTAL

Participants receive 180 µg of frespaciguat once daily (QD) via inhalation from Days 1-7.

Drug: Frespaciguat

Panel A Placebo

PLACEBO COMPARATOR

Participants receive frespaciguat-matching placebo QD via inhalation from Days 1-7.

Drug: Placebo

Panel B Frespaciguat 360 µg

EXPERIMENTAL

Participants receive 360 µg of frespaciguat QD via inhalation from Days 1-7.

Drug: Frespaciguat

Panel B Placebo

PLACEBO COMPARATOR

Participants receive frespaciguat-matching placebo QD via inhalation from Days 1-7.

Drug: Placebo

Panel C Frespaciguat ≤360 µg

EXPERIMENTAL

Participants receive ≤360 µg of frespaciguat QD via inhalation from Days 1-7.

Drug: Frespaciguat

Panel C Placebo

PLACEBO COMPARATOR

Participants receive frespaciguat-matching placebo QD via inhalation from Days 1-7.

Drug: Placebo

Interventions

Frespaciguat DRUG

Frespaciguat administered at a dose of 180 µg or ≤360 µg QD via inhalation

Also known as: MK-5475

Panel A Frespaciguat 180 µg; Panel B Frespaciguat 360 µg; Panel C Frespaciguat ≤360 µg

Placebo DRUG

Frespaciguat-matching placebo administered QD via inhalation

Panel A Placebo; Panel B Placebo; Panel C Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

COVID-19; Pneumonia; Hypoxia

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 11, 2020
• Study Start: July 7, 2020
• Primary Completion: November 10, 2020
• Study Completion: November 10, 2020
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share