Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19)
Condition: COVID-19
MeSH terms: COVID-19; Alpha 1-Antitrypsin Deficiency
Intervention: Liquid Alpha1-Proteinase Inhibitor (Human); Placebo; Standard Medical Treatment
Intervention description: Intravenous infusion 120 mg/kg; Intravenous infusion; SMT
Intervention MeSH terms: Protease Inhibitors; Alpha 1-Antitrypsin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Coronavirus Disease; Severe acute respiratory syndrome coronavirus 2; SARS-CoV-2

Summary:

      The purpose of the study is to determine if Liquid Alpha1-Proteinase Inhibitor (Human)
      (Liquid Alpha1-PI) plus SMT can reduce the proportion of participants dying or requiring
      intensive care unit (ICU) admission on or before Day 29 or who are dependent on high flow
      oxygen devices or invasive mechanical ventilation on Day 29 versus placebo plus SMT in
      hospitalized participants with COVID-19.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Hospitalized male or female participant ≥ 18 years of age at time of screening who is
             being treated for COVID-19. Participants must be screened within 48 hours (≤ 48 hours)
             of hospital admission.

          2. Has laboratory-confirmed novel coronavirus {SARS-CoV-2} infection as determined by
             qualitative polymerase chain reaction (PCR) (reverse transcriptase [RT]-PCR), or other
             commercial or public health assay approved by regulatory authorities as a diagnostic
             test for COVID-19 in any specimen during the current hospital admission OR 96 hours
             prior to the hospital admission date and prior to randomization (the SARS-CoV-2 test
             results must be performed by a hospital laboratory and the documentation available).

          3. COVID-19 illness (symptoms) of any duration, including both of the following: a)
             Radiographic infiltrates by imaging (chest X-Ray, computed tomography (CT) scan, etc.)
             and/or clinical assessment (evidence of rales/crackles on exam) with peripheral oxygen
             saturation by pulse oximetry (SpO2) <94% on room air; b) Any one of the following
             related to COVID-19: i. Ferritin > 400 nanogram per milliliter (ng/mL), ii. lactate
             dehydrogenase (LDH) > 300 units per liter (U/L), iii. D-Dimers > reference range, or
             iv. C-reactive protein (CRP) > 40 milligram per liter (mg/L).

          4. Participant provides informed consent prior to initiation of any study procedures.

          5. Female participants of childbearing potential (and males with female partners of
             childbearing potential) must agree to use of acceptable contraception methods during
             study (example, oral, injectable, or implanted hormonal methods of contraception,
             placement of an intrauterine device or intrauterine system, condom or occlusive cap
             with spermicidal foam/gel/film/cream/suppository, male sterilization, or true
             abstinence) throughout the study.

        Exclusion Criteria:

          1. Participants requiring invasive mechanical ventilation or ICU admission or with
             partial pressure of arterial oxygen/ fraction of inspired oxygen (PaO2/FIO2) ≤ 150
             mmHg (i.e., arterial oxygen in millimeter of mercury (mmHg) divided by fraction
             inspired oxygen concentration [example, 0.21 for room air]).

          2. Clinical evidence of any significant acute or chronic disease that, in the opinion of
             the investigator, may place the participant at undue medical risk.

          3. The participant has had a known serious anaphylactic reaction to blood, any
             blood-derived or plasma product, or known selective immunoglobulin A (IgA) deficiency
             with anti-IgA antibodies.

          4. A medical condition in which the infusion of additional fluid is contraindicated
             (example, decompensated congestive heart failure or renal failure with fluid
             overload). This includes currently uncontrolled congestive heart failure New York
             Heart Association Class III or IV stage heart failure.

          5. Shock that is unresponsive to fluid challenge and/or multiple vasopressors and
             accompanied by multiorgan failure considered not able to be reversed by the Principal
             Investigator.

          6. Known alpha-1 antitrypsin deficiency for which the participant is already receiving
             alpha1-proteinase inhibitor augmentation therapy.

          7. Women who are pregnant or breastfeeding. Female participants of child-bearing
             potential must have a negative test for pregnancy blood or urine human chorionic
             gonadotropin (HCG)-based assay at screening/baseline visit.

          8. Participants for whom there is limitation of therapeutic effort such as "Do not
             resuscitate" status.

          9. Currently participating in another interventional clinical trial with investigational
             medical product or device.

         10. Participants previously requiring long-term oxygen therapy (home oxygen therapy).

         11. History (within the last 2 years) of myocardial infarction, unstable angina, stroke or
             transient ischemic attacks, pulmonary embolism or deep venous thrombosis.

         12. Participant has medical condition (other than COVID-19) that is projected to limit
             lifespan to ≤ 1 year.

         13. Systolic blood pressure < 100 mm Hg or > 160 mm Hg (uncontrolled hypertension) at the
             time of Screening.

         14. Alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN).

         15. Any elevation of total bilirubin at the time of Screening.

         16. Estimated glomerular filtration rate (eGFR) < 45 mL/min (or participant is dependent
             on dialysis/renal replacement therapy) at the time of Screening. eGFR is calculated by
             the Cockcroft-Gault equation.

         17. Hemoglobin < 10 g/dL at the time of Screening.

         18. Absolute neutrophil count < 1000/mm^3 at the time of Screening.

         19. Platelet count < 75,000/mm^3 at the time of Screening.

         20. Participant has history of drug or alcohol abuse within the past 24 months.

         21. Participant is unwilling to commit to follow-up visits.

         22. Known history of prothrombin gene mutation 20210, homozygous Factor V Leiden
             mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or
             antiphospholipid syndrome.