A Phase II/III Study of Sargramostim

• Sargramostim (Drug), also known as Leukine: 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.
• Placebo (Drug): 2 mL of physiological saline will be administered using inhaler twice daily in approximately 10-15 minutes.

Primary outcomes

• 2-rank Improvement on a 7-point Ordinal Scale [Period until Day 28 (including the case after discharge).]: Number of days to achieve at least 2-rank improvement on a 7-point ordinal scale from baseline until Day 28.

Secondary outcomes

• Changes From Baseline in Alveolar-arterial Oxygen Partial Pressure Gradient (A-aDO) [Period until Day 28 (including the case after discharge).]: Changes from baseline in alveolar-arterial oxygen partial pressure gradient (A-aDO) on Day 5 and at the end of administration.
• Number of Days Until Discharge From Baseline [Period until Day 28 (including the case after discharge).]: Number of days until discharge from baseline (days of shifting to Category 7 on a 7-point ordinal scale).
• Proportion of Subjects Whose Category Has Shifted to Category 1 or 2 [Period until Day 28 (including the case after discharge).]: Proportion of subjects whose category has shifted to Category 1 or 2 on a 7-point ordinal scale from baseline until Day 28

Sex: All, ages: 20 Years to 85 Years

Inclusion Criteria:

Japanese male or female subjects who have been confirmed to meet all the following criteria.

1. Hospitalized patients under treatment who were severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2\] positive by polymerase chain reaction (PCR) test.
2. Patients with clinically diagnosed pneumonia and a percutaneous oxygen saturation \[SpO2\] of 93% or less on breathing of room air at bed rest.
3. Patients for whom written informed consent has been obtained from those themselves or the legally acceptable representatives.
4. 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.

1. Patients who have been participating in other intervention studies, such as studies on unapproved pharmacotherapy, within 90 days prior to screening.
2. 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.
3. Patients who are not expected to survive longer than 24 hours after commencement of study drug administration.
4. Patients who are using invasive ventilator or extracorporeal membrane oxygenation (ECMO).
5. Patients who have a chronic respiratory disease requiring continuous home oxygen therapy or ventilator use.
6. 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).
7. 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.
8. Patients who have a disease including leukemia and leukocytosis that causes leukocytosis.
9. Patients who have a chronic kidney disease requiring dialysis.
10. Patients who have severe liver failure (Child Pugh grade C).
11. Patients aged 80 years or older with any of heart failure, cerebrovascular disease, obesity (BMI 30 or higher), dyslipidemia, hypertension or diabetes.

Participant flow

Outcome results

• 2-rank Improvement on a 7-point Ordinal Scale (Primary), Median, Number of Days: NPC-26 9 (8 to 9); NP-26 Placebo 8 (7 to 10)
• Changes From Baseline in Alveolar-arterial Oxygen Partial Pressure Gradient (A-aDO) (Secondary)
• Number of Days Until Discharge From Baseline (Secondary)
• Proportion of Subjects Whose Category Has Shifted to Category 1 or 2 (Secondary)

Adverse events

Time frame: Day1-28

Serious adverse events by term

Other adverse events by term

• Results publication: Shimasaki S, Baba T, Ogura T, Akasaka K, Matsushima H, Izumi S, Takasaki J, Tsushima K, Kinouchi T, Kichikawa Y, Awashima M, Izumo T, Awano N, Nishimura N, Tazawa R, Mikami A, Kitamura N, Ishii H, Kurihara Y, Taniguchi M, Aikawa S, Okada M, Morita Y, Ishikawa Y, Ohinata A, Nakata K. Short-term inhalation of sargramostim with concomitant high-dose steroids does not hasten recovery in moderate COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial. Infect Dis (Lond). 2023 Dec;55(12):857-873. doi: 10.1080/23744235.2023.2254380. Epub 2023 Oct 6. PMID 37729076

• Study Protocol (PDF, 2021-04-22)
• Statistical Analysis Plan (PDF, 2021-12-16)