- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04547140
Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19)
March 17, 2023 updated by: Grifols Therapeutics LLC
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
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
57
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Blumenau, Brazil, 89030-101
- Hospital Dia do Pulmao
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São Paulo, Brazil, 01327-001
- Hospital Alemao Oswaldo Cruz
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São Paulo, Brazil, 04037-002
- Universidade Federal de Sao Paulo
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Santa Catarina
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Blumenau, Santa Catarina, Brazil, 89020-430
- AngioCor Blumenau
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Criciúma, Santa Catarina, Brazil, 88811-500
- Sociedade Literaria e Caritativa Santo Agostinho
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São Paulo
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Botucatu, São Paulo, Brazil, 18618-686
- Universidade Estadual São Paulo - Campus de Botucatu
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Santiago, Chile, 8860000
- Hospital Padre Hurtado
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Valparaíso, Chile, 2340000
- Hospital Carlos Van Buren
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Santander
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Bucaramanga, Santander, Colombia
- Fundacion Oftalmologica De Santander
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San Nicolás de los Garza, Mexico, 66465
- Unidad Médica para la Salud Integral
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Alabama
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Birmingham, Alabama, United States, 35233
- Birmingham VA
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Arizona
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Phoenix, Arizona, United States, 85013
- St. Joseph's Hospital
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Florida
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Miami, Florida, United States, 33125
- University of Miami Hospital
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Michigan
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Lansing, Michigan, United States, 48912
- Sparrow Hospital
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Missouri
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Hannibal, Missouri, United States, 63401
- Hannibal Clinic
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Kansas City, Missouri, United States, 64128
- Kansas City VA
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Nebraska
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Omaha, Nebraska, United States, 68102
- CHI Health Center
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New York
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New York, New York, United States, 10032
- Columbia University Medical Center
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Tennessee
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Memphis, Tennessee, United States, 38104
- Memphis VA
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Utah
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Salt Lake City, Utah, United States, 84108
- University of Utah
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
- 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).
- 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).
- Participant provides informed consent prior to initiation of any study procedures.
- 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:
- 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]).
- Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may place the participant at undue medical risk.
- 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.
- 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.
- 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.
- Known alpha-1 antitrypsin deficiency for which the participant is already receiving alpha1-proteinase inhibitor augmentation therapy.
- 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.
- Participants for whom there is limitation of therapeutic effort such as "Do not resuscitate" status.
- Currently participating in another interventional clinical trial with investigational medical product or device.
- Participants previously requiring long-term oxygen therapy (home oxygen therapy).
- History (within the last 2 years) of myocardial infarction, unstable angina, stroke or transient ischemic attacks, pulmonary embolism or deep venous thrombosis.
- Participant has medical condition (other than COVID-19) that is projected to limit lifespan to ≤ 1 year.
- Systolic blood pressure < 100 mm Hg or > 160 mm Hg (uncontrolled hypertension) at the time of Screening.
- Alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN).
- Any elevation of total bilirubin at the time of Screening.
- 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.
- Hemoglobin < 10 g/dL at the time of Screening.
- Absolute neutrophil count < 1000/mm^3 at the time of Screening.
- Platelet count < 75,000/mm^3 at the time of Screening.
- Participant has history of drug or alcohol abuse within the past 24 months.
- Participant is unwilling to commit to follow-up visits.
- Known history of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Liquid Alpha1-Proteinase Inhibitor + Standard Medical Treatment
Participants received the first intravenous (IV) infusion of liquid alpha1-proteinase inhibitor (human) 120 milligrams 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 (second dose was not mandatory and was given at the principal investigator's [PI] discretion).
Participants also received all standard of care interventions while hospitalized, from Day 1 to Day 29.
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SMT
Intravenous infusion 120 mg/kg
Other Names:
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Placebo Comparator: Placebo + Standard Medical Treatment
Participants received 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 (Day 8 was not mandatory and was given at the PI's discretion).
Participants also received all standard of care interventions while hospitalized, from Day 1 to Day 29.
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Intravenous infusion
Other Names:
SMT
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission
Time Frame: Up to Day 29
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Up to Day 29
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Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation
Time Frame: Day 29
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Day 29
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in National Early Warning Score (NEWS)
Time Frame: Baseline, Days 15 and 29
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NEWS is clinical scoring developed to improve detection of deterioration in ill participant.
It is based on 7 clinical parameters: Respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure (BP), pulse rate, level of consciousness, and temperature.
A score of 0 and 2 was allocated to supplemental oxygen, 0 and 3 for level of consciousness and score of 0, 1, 2 and 3 for remaining parameters (i.e.
respiration rate, oxygen saturation, systolic BP, pulse rate and temperature) where 0 = normal health condition to 3 = worst health condition; Higher scores indicated more severity.
All scores were summed to get an aggregate score.
Aggregate NEWS score ranged from 0 to 20, with higher scores indicating more severity/higher risk.
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Baseline, Days 15 and 29
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Time to Clinical Response as Assessed by NEWS Score ≤ 2 Maintained for 24 Hours
Time Frame: Up to Day 29
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Time to clinical response was reported at 50th percentile in days.
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Up to Day 29
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Time to Hospital Discharge
Time Frame: Up to Day 29
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Time to hospital discharge is defined as duration of hospitalization from Day 1 through Day 29.
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Up to Day 29
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Duration of ICU Stay
Time Frame: Up to Day 29
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Duration of ICU stay in days is analyzed for participants admitted to ICU post randomization.
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Up to Day 29
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Duration of Any Oxygen Use
Time Frame: Up to Day 30
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Up to Day 30
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Duration of Mechanical Ventilation
Time Frame: Up to Day 29
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Duration of Mechanical Ventilation is analyzed for participants requiring mechanical ventilation post randomization.
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Up to Day 29
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Mean Change From Baseline in Ordinal Scale
Time Frame: Baseline, Days 15 and 29
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The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Higher score indicated no severe illness.
Mean change in Ordinal scale was evaluated by fitting a linear mixed-effects model for repeated measures (MMRM).
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Baseline, Days 15 and 29
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Absolute Change From Baseline in Ordinal Scale
Time Frame: Baseline, Days 15 and 29
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The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Higher score indicated no severe illness.
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Baseline, Days 15 and 29
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Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale
Time Frame: Day 15 and Day 29
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The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
The percentages are rounded off to the single decimal point.
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Day 15 and Day 29
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Time to Sustained Normalization of Temperature
Time Frame: Up to Day 29
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Time to sustained normalization of temperature was reported at 50th percentile in days.
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Up to Day 29
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Percentage of Participants Who Experienced Sustained Normalization of Fever
Time Frame: Up to Day 29
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Normalization of fever is defined as temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for at least 24 hours.
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Up to Day 29
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Number of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS)
Time Frame: Up to Day 29
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ARDS was defined based on Berlin criteria (chest imaging, origin of edema, oxygenation).
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Up to Day 29
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Time to Clinical Progression
Time Frame: Up to Day 29
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Time to clinical progression is defined as the time to death, mechanical ventilation, or ICU admission.
Time to clinical progression was reported at 50th percentile in days.
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Up to Day 29
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 29, 2021
Primary Completion (Actual)
December 13, 2021
Study Completion (Actual)
January 28, 2022
Study Registration Dates
First Submitted
September 10, 2020
First Submitted That Met QC Criteria
September 10, 2020
First Posted (Actual)
September 14, 2020
Study Record Updates
Last Update Posted (Actual)
March 22, 2023
Last Update Submitted That Met QC Criteria
March 17, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- Liver Diseases
- Genetic Diseases, Inborn
- Subcutaneous Emphysema
- Emphysema
- COVID-19
- Alpha 1-Antitrypsin Deficiency
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Serine Proteinase Inhibitors
- Trypsin Inhibitors
- Protease Inhibitors
- Alpha 1-Antitrypsin
Other Study ID Numbers
- GC2006
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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