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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate safety, tolerability, and pharmacodynamics of MK-5475 after administration of multiple doses to participants with COVID-19 pneumonia. The primary hypothesis is that MK-5475 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.

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

Conditions
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Pneumonia, Coronavirus Disease 2019 (COVID-19), Hypoxemia

Intervention / Treatment
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* Drug: MK-5475
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 MK-5475 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Sequential Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |