A Phase II/III Study of Sargramostim

Study Overview
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Brief Summary
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This is a randomized, placebo-controlled, double-blind, group comparison, multicenter study to evaluate the efficacy and safety of inhalation administration of sargramostim for 5 days, in principle (up to 10 days) as Add-on treatment to the standard treatment in COVID-19 patients.

Official Title
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A Phase II/III Study of Sargramostim in Patients With Coronavirus Disease-2019 (COVID-19)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Sargramostim
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese male or female subjects who have been confirmed to meet all the following criteria. Hospitalized patients under treatment who were severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] positive by polymerase chain reaction (PCR) test. Patients with clinically diagnosed pneumonia and a percutaneous oxygen saturation [SpO2] of 93% or less on breathing of room air at bed rest. Patients for whom written informed consent has been obtained from those themselves or the legally acceptable representatives. Patients aged 20 years or older and younger than 85 years at the time of obtaining informed consent. Exclusion Criteria: Subjects who meet any of the following criteria will be excluded. Unless otherwise stated, the following criteria refer to those at the time of screening. Patients who have been participating in other intervention studies, such as studies on unapproved pharmacotherapy, within 90 days prior to screening. Patients who have experienced off-label use of approved drugs (including those for COVID-19 treatment other than steroids as standard treatment) within 7 days prior to screening. Patients who are not expected to survive longer than 24 hours after commencement of study drug administration. Patients who are using invasive ventilator or extracorporeal membrane oxygenation (ECMO). Patients who have a chronic respiratory disease requiring continuous home oxygen therapy or ventilator use. Patients with an underlying condition that is considered very unlikely to withdraw ventilator (e.g., motor neuron disease, Duchenne muscular dystrophy, rapidly progressive interstitial pulmonary fibrosis). Patients who have a disease including bronchial asthma, lower respiratory tract infections, and interstitial lung diseases that may affect the assessment of the clinical study, since before the symptom onset of COVID-19. Patients who have a disease including leukemia and leukocytosis that causes leukocytosis. Patients who have a chronic kidney disease requiring dialysis. Patients who have severe liver failure (Child Pugh grade C). Patients aged 80 years or older with any of heart failure, cerebrovascular disease, obesity (BMI 30 or higher), dyslipidemia, hypertension or diabetes.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPC-26<br>Sargramostim (125 μg) will be administered by inhalation twice daily for 5 days, in principle (up to 10 days) as Add-on treatment to the standard treatment. | Drug: Sargramostim<br>* 250 μg/vial of sargramostim will be dissolved in 4 mL of physiological saline and 125 μg of which will be administered using inhaler twice daily in approximately 10-15 minutes.<br>* Other names: Leukine;|
| Placebo Comparator: NP-26 Placebo<br>Physiological saline will be administered by inhalation twice daily for 5 days, in principle (up to 10 days) as Add-on treatment to the standard treatment. | Drug: Placebo<br>* 2 mL of physiological saline will be administered using inhaler twice daily in approximately 10-15 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-rank improvement on a 7-point ordinal scale | Number of days to achieve at least 2-rank improvement on a 7-point ordinal scale from baseline until Day 28. | Period until Day 28 (including the case after discharge). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in alveolar-arterial oxygen partial pressure gradient (A-aDO) | Changes from baseline in alveolar-arterial oxygen partial pressure gradient (A-aDO) on Day 5 and at the end of administration. | Period until Day 28 (including the case after discharge). | 
| Number of days until discharge from baseline | Number of days until discharge from baseline (days of shifting to Category 7 on a 7-point ordinal scale). | Period until Day 28 (including the case after discharge). | 
| Proportion of subjects whose category has shifted to Category 1 or 2 | Proportion of subjects whose category has shifted to Category 1 or 2 on a 7-point ordinal scale from baseline until Day 28 | Period until Day 28 (including the case after discharge). |