Covid19, Pneumonia, Viral
Conditions
Brief summary
This is a Randomized, Open-Label Study of the Efficacy and Safety of Aralast NP Infusion Therapy with Antiviral Treatment and standard of care versus Antiviral Treatment and standard of care (control group) in Hospitalized Patients with Pneumonia and COVID-19 Infection.
Detailed description
Approximately 20 subjects in total will be randomized with 1:1 ratio to the high dose of Aralast NP infusion therapy plus antiviral and standard of care versus antiviral therapy and standard of care. Each subject will participate in the study for 24 days and have one safety follow-up phone call at 30 days. Active treatment will last 17 days, subject will be dosed on Days 1, 3, 5, 7, 9 and have a final booster infusion on Day 17. If the subject is discharged from hospital, any remaining infusions and assessments will be conducted via outpatient clinic visit or home health visit. Subjects will have an in-person visit (hospital or clinic) on Day 24 for a CT scan and follow-up assessment. Efficacy will be evaluated by measuring the duration of new non-invasive ventilation or high flow oxygen used. Additional endpoints include clinical status, cytokine levels, oxygen requirements, SOFA scores, risk of coagulopathy, need for Vasopressors, mortality during the treatment period, PK samples, average days spent in the hospital/ICU, and number of days without a fever.
Interventions
Alpha1-Proteinase Inhibitor (Human), AralastÔ, is a sterile, stable, lyophilized preparation of purified human alpha1-proteinase inhibitor (a1-PI), also known as alpha1-antitrypsin.
DRUGAntiviral Agents
a SARS-CoV-2 nucleotide analog RNA polymerase inhibitor indicated for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of coronavirus disease 2019 (COVID-19) requiring hospitalization
Sponsors
Takeda Pharmaceuticals North America, Inc.
Blessing Corporate Services, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized with 1:1 ratio to the high dose of Aralast NP infusion therapy plus antiviral and standard of care versus antiviral therapy and standard of care.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject will sign and date an informed consent form. 2. Hospitalized subjects will be 18 years of age or older. 3. Lab confirmed positive for COVID-19 within 72 hours prior to randomization. 4. Subjects with COVID-19 with evidence of pneumonia (diagnosed by a chest x-ray) on supplemental oxygen or non-invasive ventilation with PO2/FiO2 ratio less than 300. 5. Subject must have one of the following elevated inflammatory markers: C-reactive protein \>40mg/L; D-Dimers \> 250ng/mL DDU or \>0.5mcg/mL FEU; Ferritin \>400ng/mL; LDH \>300U/L.
Exclusion criteria
1. Subject is on mechanical ventilation at time of screening. 2. Subject is not expected to survive greater than 48 hours from screening based on PI judgement. 3. Prior or current treatment with anti-IL-6, anti-IL-6 R antagonist or JAK inhibitors. 4. Subject is on immunosuppressive agents, with the exception of corticosteroids for severe COVID-19 patients at the discretion of the PI. 5. Subject is currently participating in a trial for any other investigational drug. 6. Subject is on another plasma derived product or has received plasma or blood products within the last 48 hours. 7. Subject is pregnant or breastfeeding. 8. The subject, or the next of kin/power of attorney are not able to give the proper informed consent. 9. The subject has a known IgA deficiency with anti-IgA antibodies. 10. Subject has a known Alpha-1 Antitrypsin Deficiency. 11. Subject has antibodies against alpha-1 proteinase inhibitor 12. Subject has renal, liver or multisystem organ failure 13. Subject has known history of hypersensitivity following infusions of human blood or blood components (eg, human immunoglobulins or human albumin). 14. Positive serological test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Duration of new non-invasive ventilation or high flow oxygen use (measured by days) | 365 Days |
Secondary
| Measure | Time frame |
|---|---|
| The percent of patients with a SOFA score between 0-6 during treatment period. | 1 Year |
| To evaluate the average number of days in the ICU | 1 Year |
| To evaluate the average number of days in the hospital | 1 Year |
| To evaluate the number of days with a PO2/FiO2 <300 or other parameters decided on with oxygen | 1 Year |
| The risk of coagulopathy by measuring Prothrombin time & Partial Thromboplastin time | 1 Year |
| The risk of coagulopathy by measuring D-Dimer | 1 Year |
| The risk of coagulopathy by measuring Platelet Counts | 1 Year |
| Clinical status on a 7-point ordinal scale (from 1=death to 7=not hospitalized | 1 Year |
| The percentage change in cytokine levels from screening through day 10, Day 17 and Day 24 | 10 Days, 17 Days, & 24 Days |
| The percentage change in oxygen requirements including PEEP and FiO2 from screening through day 10. | 10 Days |
| The percentage of subjects that required mechanical ventilation during the treatment period. | 1 Year |
| The percent of mortality during the treatment period. | 1 Year |
| Evaluate the need, dosage and duration of vasopressors (number of days and average daily dose). | 1 Year |
| Number of Days fever free (defined by temperature of <100°F (oral) for 24 hours) | 1 Year |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maximal expiratory pressure (MEP) at Day 10, Day 17, and Day 24. | 10 Days, 17 Days, & 24 Days | — |
| Muscle strength assessment at Day 10, Day 17 and Day 24. | 10 Days, 17 Days, & 24 Days | — |
| Correlation between plasma exposure of Aralast NP (Pharmacokinetics) and the other listed clinical endpoints at Days 1, 3, 5, 7, 9 and 17. | 1 Day, 3 Days, 5 Days, 7 Days, 9 Days, & 17 Days | Pharmacokinetics of Aralast NP levels will be drawn to determine if there is a correlation between that and the other endpoints listed above. |
| Correlation between plasma exposure of Aralast NP (Pharmacokinetics) and biomarker endpoints (Pharmacodynamics) at Days 1, 6, 10 and 17 | 1 Day, 6 Days, 10 Days, & 17 Days | — |
| The percentage of patients with lung fibrosis or worsening of lung fibrosis from screening to Day 10 and Day 24 (as assessed by CT). | 10 Days, 17 Days, & 24 Days | — |
| Maximal inspiratory pressure (MIP) at Day 10, Day 17 and Day 24. | 10 Days, 17 Days, & 24 Days | — |
Countries
United States
Outcome results
None listed