COVID-19
Conditions
Brief summary
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.
Interventions
DRUGSargramostim
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.
DRUGPlacebo
2 mL of physiological saline will be administered using inhaler twice daily in approximately 10-15 minutes.
Sponsors
Nobelpharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NP-26 Placebo 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. | 23 |
| NPC-26 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. | 47 |
| Total | 70 |
Baseline characteristics
| Characteristic | NPC-26 | Total | NP-26 Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 14 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 56 Participants | 21 Participants |
| Age, Continuous | 54.1 years STANDARD_DEVIATION 12.5 | 54.7 years STANDARD_DEVIATION 11.3 | 55.9 years STANDARD_DEVIATION 8.3 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Japan | 47 participants | 70 participants | 23 participants |
| Sex: Female, Male Female | 9 Participants | 18 Participants | 9 Participants |
| Sex: Female, Male Male | 38 Participants | 52 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 23 |
| other Total, other adverse events | 22 / 47 | 8 / 23 |
| serious Total, serious adverse events | 2 / 47 | 0 / 23 |
Outcome results
Primary
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.
Time frame: Period until Day 28 (including the case after discharge).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NPC-26 | 2-rank Improvement on a 7-point Ordinal Scale | 9 Number of Days |
| NP-26 Placebo | 2-rank Improvement on a 7-point Ordinal Scale | 8 Number of Days |
Secondary
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.
Time frame: Period until Day 28 (including the case after discharge).
Secondary
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).
Time frame: Period until Day 28 (including the case after discharge).
Secondary
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
Time frame: Period until Day 28 (including the case after discharge).