Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19)

• Status: Recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Grifols Therapeutics LLC
• Treatments: Alpha 1-Antitrypsin; Protease Inhibitors

Criteria

Inclusion Criteria:

1. Hospitalized male or female subject ≥ 18 years of age at time of screening who is being treated for COVID-19. Subjects 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. Subject provides informed consent prior to initiation of any study procedures.

5. Female subjects 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. Subjects 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 subject at undue medical risk.

3. The subject 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 subject is already receiving alpha1-proteinase inhibitor augmentation therapy.

7. Women who are pregnant or breastfeeding. Female subjects 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. Subjects 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. Subjects 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. Subject 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 subject is dependent on dialysis/renal replacement therapy) at the time of Screening

17. Hemoglobin < 10 g/dL at the time of Screening

18. Absolute neutrophil count < 1000/mm3 at the time of Screening

19. Platelet count < 75,000/mm3 at the time of Screening

20. Subject has history of drug or alcohol abuse within the past 24 months

21. Subject 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