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

• ClinicalTrials.gov Identifier: NCT04547140
• Recruitment Status: Terminated
• First Posted: September 14, 2020
• Last Update Posted: April 19, 2022
• Sponsor: Grifols Therapeutics LLC
• Information provided by (Responsible Party): Grifols Therapeutics LLC

Tracking Information

• First Submitted Date: September 10, 2020
• First Posted Date: September 14, 2020
• Last Update Posted Date: April 19, 2022
• Actual Study Start Date: January 29, 2021
• Actual Primary Completion Date: December 13, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 10, 2020)

• Percentage of Participants Dying or Requiring ICU Admission [ Time Frame: Up to Day 29 ]
• Percentage of Participants Who are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation [ Time Frame: Day 29 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 10, 2020)

• Change from Baseline in National Early Warning Score (NEWS) [ Time Frame: Day 1 through Day 29 ]
• Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours [ Time Frame: Day 1 through Day 29 ]
• Time to Hospital Discharge [ Time Frame: Day 1 through Day 29 ]
• Duration of ICU Stay [ Time Frame: Up to Day 29 ]
• Duration of Any Oxygen Use [ Time Frame: Day 1 through Day 29 ]
• Duration of Mechanical Ventilation [ Time Frame: Up to Day 29 ]
• Mean Change from Baseline in Ordinal Scale [ Time Frame: Day 1 through Day 29 ]
• Absolute Value Change from Baseline in Ordinal Scale [ Time Frame: Day 1 through Day 29 ]
• Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale [ Time Frame: Day 15 and Day 29 ]
• Time to Sustained Normalization of Temperature [ Time Frame: Up to Day 29 ]
• Percentage of Participants with Normalization of Fever [ Time Frame: Up to Day 29 ]
• Number of Participants who Develop Acute Respiratory Distress Syndrome (ARDS) [ Time Frame: Up to Day 29 ]
• Length of Time to Clinical Progression [ Time Frame: Up to Day 29 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19)
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) Plus Standard Medical Treatment (SMT) Versus Placebo Plus SMT in Hospitalized Subjects With COVID-19
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Biological: Liquid Alpha1-Proteinase Inhibitor (Human)
  Intravenous infusion 120 mg/kg
  Other Name: Alpha1-proteinase inhibitor
• Drug: Placebo
  Intravenous infusion
  Other Name: 0.9% Normal Saline
• Drug: Standard Medical Treatment
  SMT

Study Arms

• Experimental: Liquid Alpha1-Proteinase Inhibitor+Standard Medical Treatment
  Participants will receive the first Intravenous (IV) infusion of liquid alpha1-proteinase inhibitor (human) (120 milligram per kilogram [mg/kg]), based on body weight on Day 1, followed by second liquid alpha1-proteinase inhibitor (human) dose of 120 mg/kg based on body weight, on Day 8. Participants will also receive all standard of care interventions while hospitalized, from Day 1 to Day 29.
  Interventions:

  • Biological: Liquid Alpha1-Proteinase Inhibitor (Human)
  • Drug: Standard Medical Treatment
• Placebo Comparator: Placebo+Standard Medical Treatment
  Participants will receive IV infusions of 0.9% Normal Saline of commensurate volume to that of liquid alpha1-proteinase inhibitor as placebo on Day 1 and Day 8 Participants will also receive all standard of care interventions while hospitalized, from Day 1 to Day 29.
  Interventions:

  • Drug: Placebo
  • Drug: Standard Medical Treatment

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 12, 2022): 54
• Original Estimated Enrollment (submitted: September 10, 2020): 100
• Actual Study Completion Date: January 28, 2022
• Actual Primary Completion Date: December 13, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Chile, Colombia, Mexico, United States

Administrative Information

• NCT Number: NCT04547140
• Other Study ID Numbers: GC2006
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Grifols Therapeutics LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Grifols Therapeutics LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Grifols Therapeutics LLC
• Verification Date: April 2022