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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04547140
Recruitment Status : Recruiting
First Posted : September 14, 2020
Last Update Posted : November 16, 2020
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

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.

Condition or disease Intervention/treatment Phase
COVID-19 Biological: Liquid Alpha1-Proteinase Inhibitor (Human) Drug: Placebo Drug: Standard Medical Treatment Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : September 2021


Arm Intervention/treatment
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.
Biological: Liquid Alpha1-Proteinase Inhibitor (Human)
Intravenous infusion 120 mg/kg
Other Name: Alpha1-proteinase inhibitor

Drug: Standard Medical Treatment
SMT

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.
Drug: Placebo
Intravenous infusion
Other Name: 0.9% Normal Saline

Drug: Standard Medical Treatment
SMT




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

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


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 prior to randomization.
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04547140


Contacts
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Contact: Susan Sorrells 919-316-6582 susan.sorrells@grifols.com
Contact: Elsa Mondou 919-316-2079 elsa.mondou@grifols.com

Locations
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United States, Nebraska
CHI Health Center Recruiting
Omaha, Nebraska, United States, 68102
Contact: Bryan Krajicek, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Monica Goldklang, MD         
Sponsors and Collaborators
Grifols Therapeutics LLC
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Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT04547140    
Other Study ID Numbers: GC2006
First Posted: September 14, 2020    Key Record Dates
Last Update Posted: November 16, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Grifols Therapeutics LLC:
Coronavirus Disease
Severe acute respiratory syndrome coronavirus 2
SARS-CoV-2
Additional relevant MeSH terms:
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Alpha 1-Antitrypsin Deficiency
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Protease Inhibitors
Alpha 1-Antitrypsin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors
Serine Proteinase Inhibitors