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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04547140
Recruitment Status : Terminated (Study Stopped for Futility)
First Posted : September 14, 2020
Last Update Posted : April 19, 2022
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Tracking Information
First Submitted Date  ICMJE September 10, 2020
First Posted Date  ICMJE September 14, 2020
Last Update Posted Date April 19, 2022
Actual Study Start Date  ICMJE January 29, 2021
Actual Primary Completion Date December 13, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 12, 2022)
54
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2020)
100
Actual Study Completion Date  ICMJE January 28, 2022
Actual Primary Completion Date December 13, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Chile,   Colombia,   Mexico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04547140
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Current Responsible Party Grifols Therapeutics LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Grifols Therapeutics LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Grifols Therapeutics LLC
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP