Back to resultsAralast NP With Antiviral Treatment and Standard of Care Versus Antiviral Treatment With Standard of Care in Hospitalized Patients With Pneumonia and COVID-19 Infection
Primary Purpose
Covid19, Pneumonia, Viral
Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
alpha1-proteinase inhibitor
Antiviral Agents
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility Criteria
Inclusion Criteria
- Subject will sign and date an informed consent form.
- Hospitalized subjects will be 18 years of age or older.
- Lab confirmed positive for COVID-19 within 72 hours prior to randomization.
- Subjects with COVID-19 with evidence of pneumonia (diagnosed by a chest x-ray) on supplemental oxygen or non-invasive ventilation with PO2/FiO2 ratio less than 300.
- Subject must have one of the following elevated inflammatory markers: C-reactive protein >40mg/L; D-Dimers > 250ng/mL DDU or >0.5mcg/mL FEU; Ferritin >400ng/mL; LDH >300U/L.
Exclusion Criteria
- Subject is on mechanical ventilation at time of screening.
- Subject is not expected to survive greater than 48 hours from screening based on PI judgement.
- Prior or current treatment with anti-IL-6, anti-IL-6 R antagonist or JAK inhibitors.
- Subject is on immunosuppressive agents, with the exception of corticosteroids for severe COVID-19 patients at the discretion of the PI.
- Subject is currently participating in a trial for any other investigational drug.
- Subject is on another plasma derived product or has received plasma or blood products within the last 48 hours.
- Subject is pregnant or breastfeeding.
- The subject, or the next of kin/power of attorney are not able to give the proper informed consent.
- The subject has a known IgA deficiency with anti-IgA antibodies.
- Subject has a known Alpha-1 Antitrypsin Deficiency.
- Subject has antibodies against alpha-1 proteinase inhibitor
- Subject has renal, liver or multisystem organ failure
- Subject has known history of hypersensitivity following infusions of human blood or blood components (eg, human immunoglobulins or human albumin).
- Positive serological test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
Sites / Locations
- Blessing Corporate Services, Inc
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Aralast NP + Antiviral Treatment + Standard of Care
Antiviral Treatment + Standard of Care
Arm Description
The investigational product is alpha1-proteinase inhibitor, administered as a loading dose of 120mg/kg/body weight intravenous infusion on the first day, and then 60mg/kg/BW intravenous infusion on Days 3, 5, 7 and 9. Booster infusion of 120 mg/kg/BWon Day 17. The Antiviral treatment is Remdesivir. For patients not requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days for a total treatment duration of up to 10 days. Recommended dosage in adults and pediatric patients 12 years of age and older and weighing at least 40 kg: a single loading dose of Remdesivir 200 mg on Day 1 followed by once-daily maintenance doses of Remdesivir 100 mg from Day 2 infused over 30 to 120 minutes Standard of Care treatments are at the investigator's discretion based on best practices.
The Antiviral treatment is Remdesivir. For patients not requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days for a total treatment duration of up to 10 days. Recommended dosage in adults and pediatric patients 12 years of age and older and weighing at least 40 kg: a single loading dose of Remdesivir 200 mg on Day 1 followed by once-daily maintenance doses of Remdesivir 100 mg from Day 2 infused over 30 to 120 minutes Standard of Care treatments are at the investigator's discretion based on best practices.
Outcomes
Primary Outcome Measures
Duration of new non-invasive ventilation or high flow oxygen use (measured by days)
Secondary Outcome Measures
Clinical status on a 7-point ordinal scale (from 1=death to 7=not hospitalized
The percentage change in cytokine levels from screening through day 10, Day 17 and Day 24
The percentage change in oxygen requirements including PEEP and FiO2 from screening through day 10.
The percentage of subjects that required mechanical ventilation during the treatment period.
The percent of patients with a SOFA score between 0-6 during treatment period.
The percent of mortality during the treatment period.
Evaluate the need, dosage and duration of vasopressors (number of days and average daily dose).
Number of Days fever free (defined by temperature of <100°F (oral) for 24 hours)
To evaluate the average number of days in the ICU
To evaluate the average number of days in the hospital
To evaluate the number of days with a PO2/FiO2 <300 or other parameters decided on with oxygen
The risk of coagulopathy by measuring Prothrombin time & Partial Thromboplastin time
The risk of coagulopathy by measuring D-Dimer
The risk of coagulopathy by measuring Platelet Counts
Full Information
NCT ID
NCT04675086
First Posted
November 25, 2020
Last Updated
December 17, 2020
Sponsor
Blessing Corporate Services, Inc
Collaborators
Takeda Pharmaceuticals North America, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04675086
Brief Title
Aralast NP With Antiviral Treatment and Standard of Care Versus Antiviral Treatment With Standard of Care in Hospitalized Patients With Pneumonia and COVID-19 Infection
Official Title
A Randomized, Open-Label Study of the Efficacy and Safety of Aralast NP, an Alpha-1 Antitrypsin Infusion Therapy With Antiviral Treatment and Standard of Care Versus Antiviral Treatment With Standard of Care in Hospitalized Patients With Pneumonia and COVID-19 Infection
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Administrative Decision
Study Start Date
January 2021 (Anticipated)
Primary Completion Date
September 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Blessing Corporate Services, Inc
Collaborators
Takeda Pharmaceuticals North America, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Randomized, Open-Label Study of the Efficacy and Safety of Aralast NP Infusion Therapy with Antiviral Treatment and standard of care versus Antiviral Treatment and standard of care (control group) in Hospitalized Patients with Pneumonia and COVID-19 Infection.
Detailed Description
Approximately 20 subjects in total will be randomized with 1:1 ratio to the high dose of Aralast NP infusion therapy plus antiviral and standard of care versus antiviral therapy and standard of care.
Each subject will participate in the study for 24 days and have one safety follow-up phone call at 30 days. Active treatment will last 17 days, subject will be dosed on Days 1, 3, 5, 7, 9 and have a final booster infusion on Day 17. If the subject is discharged from hospital, any remaining infusions and assessments will be conducted via outpatient clinic visit or home health visit. Subjects will have an in-person visit (hospital or clinic) on Day 24 for a CT scan and follow-up assessment.
Efficacy will be evaluated by measuring the duration of new non-invasive ventilation or high flow oxygen used. Additional endpoints include clinical status, cytokine levels, oxygen requirements, SOFA scores, risk of coagulopathy, need for Vasopressors, mortality during the treatment period, PK samples, average days spent in the hospital/ICU, and number of days without a fever.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Pneumonia, Viral
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized with 1:1 ratio to the high dose of Aralast NP infusion therapy plus antiviral and standard of care versus antiviral therapy and standard of care.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aralast NP + Antiviral Treatment + Standard of Care
Arm Type
Experimental
Arm Description
The investigational product is alpha1-proteinase inhibitor, administered as a loading dose of 120mg/kg/body weight intravenous infusion on the first day, and then 60mg/kg/BW intravenous infusion on Days 3, 5, 7 and 9. Booster infusion of 120 mg/kg/BWon Day 17.
The Antiviral treatment is Remdesivir. For patients not requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days for a total treatment duration of up to 10 days. Recommended dosage in adults and pediatric patients 12 years of age and older and weighing at least 40 kg: a single loading dose of Remdesivir 200 mg on Day 1 followed by once-daily maintenance doses of Remdesivir 100 mg from Day 2 infused over 30 to 120 minutes
Standard of Care treatments are at the investigator's discretion based on best practices.
Arm Title
Antiviral Treatment + Standard of Care
Arm Type
Active Comparator
Arm Description
The Antiviral treatment is Remdesivir. For patients not requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days for a total treatment duration of up to 10 days. Recommended dosage in adults and pediatric patients 12 years of age and older and weighing at least 40 kg: a single loading dose of Remdesivir 200 mg on Day 1 followed by once-daily maintenance doses of Remdesivir 100 mg from Day 2 infused over 30 to 120 minutes
Standard of Care treatments are at the investigator's discretion based on best practices.
Intervention Type
Drug
Intervention Name(s)
alpha1-proteinase inhibitor
Other Intervention Name(s)
Aralast NP
Intervention Description
Alpha1-Proteinase Inhibitor (Human), AralastÔ, is a sterile, stable, lyophilized preparation of purified human alpha1-proteinase inhibitor (a1-PI), also known as alpha1-antitrypsin.
Intervention Type
Drug
Intervention Name(s)
Antiviral Agents
Other Intervention Name(s)
Remdesivir
Intervention Description
a SARS-CoV-2 nucleotide analog RNA polymerase inhibitor indicated for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of coronavirus disease 2019 (COVID-19) requiring hospitalization
Primary Outcome Measure Information:
Title
Duration of new non-invasive ventilation or high flow oxygen use (measured by days)
Time Frame
365 Days
Secondary Outcome Measure Information:
Title
Clinical status on a 7-point ordinal scale (from 1=death to 7=not hospitalized
Time Frame
1 Year
Title
The percentage change in cytokine levels from screening through day 10, Day 17 and Day 24
Time Frame
10 Days, 17 Days, & 24 Days
Title
The percentage change in oxygen requirements including PEEP and FiO2 from screening through day 10.
Time Frame
10 Days
Title
The percentage of subjects that required mechanical ventilation during the treatment period.
Time Frame
1 Year
Title
The percent of patients with a SOFA score between 0-6 during treatment period.
Time Frame
1 Year
Title
The percent of mortality during the treatment period.
Time Frame
1 Year
Title
Evaluate the need, dosage and duration of vasopressors (number of days and average daily dose).
Time Frame
1 Year
Title
Number of Days fever free (defined by temperature of <100°F (oral) for 24 hours)
Time Frame
1 Year
Title
To evaluate the average number of days in the ICU
Time Frame
1 Year
Title
To evaluate the average number of days in the hospital
Time Frame
1 Year
Title
To evaluate the number of days with a PO2/FiO2 <300 or other parameters decided on with oxygen
Time Frame
1 Year
Title
The risk of coagulopathy by measuring Prothrombin time & Partial Thromboplastin time
Time Frame
1 Year
Title
The risk of coagulopathy by measuring D-Dimer
Time Frame
1 Year
Title
The risk of coagulopathy by measuring Platelet Counts
Time Frame
1 Year
Other Pre-specified Outcome Measures:
Title
The percentage of patients with lung fibrosis or worsening of lung fibrosis from screening to Day 10 and Day 24 (as assessed by CT).
Time Frame
10 Days, 17 Days, & 24 Days
Title
Maximal inspiratory pressure (MIP) at Day 10, Day 17 and Day 24.
Time Frame
10 Days, 17 Days, & 24 Days
Title
Maximal expiratory pressure (MEP) at Day 10, Day 17, and Day 24.
Time Frame
10 Days, 17 Days, & 24 Days
Title
Muscle strength assessment at Day 10, Day 17 and Day 24.
Time Frame
10 Days, 17 Days, & 24 Days
Title
Correlation between plasma exposure of Aralast NP (Pharmacokinetics) and the other listed clinical endpoints at Days 1, 3, 5, 7, 9 and 17.
Description
Pharmacokinetics of Aralast NP levels will be drawn to determine if there is a correlation between that and the other endpoints listed above.
Time Frame
1 Day, 3 Days, 5 Days, 7 Days, 9 Days, & 17 Days
Title
Correlation between plasma exposure of Aralast NP (Pharmacokinetics) and biomarker endpoints (Pharmacodynamics) at Days 1, 6, 10 and 17
Time Frame
1 Day, 6 Days, 10 Days, & 17 Days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Subject will sign and date an informed consent form.
Hospitalized subjects will be 18 years of age or older.
Lab confirmed positive for COVID-19 within 72 hours prior to randomization.
Subjects with COVID-19 with evidence of pneumonia (diagnosed by a chest x-ray) on supplemental oxygen or non-invasive ventilation with PO2/FiO2 ratio less than 300.
Subject must have one of the following elevated inflammatory markers: C-reactive protein >40mg/L; D-Dimers > 250ng/mL DDU or >0.5mcg/mL FEU; Ferritin >400ng/mL; LDH >300U/L.
Exclusion Criteria
Subject is on mechanical ventilation at time of screening.
Subject is not expected to survive greater than 48 hours from screening based on PI judgement.
Prior or current treatment with anti-IL-6, anti-IL-6 R antagonist or JAK inhibitors.
Subject is on immunosuppressive agents, with the exception of corticosteroids for severe COVID-19 patients at the discretion of the PI.
Subject is currently participating in a trial for any other investigational drug.
Subject is on another plasma derived product or has received plasma or blood products within the last 48 hours.
Subject is pregnant or breastfeeding.
The subject, or the next of kin/power of attorney are not able to give the proper informed consent.
The subject has a known IgA deficiency with anti-IgA antibodies.
Subject has a known Alpha-1 Antitrypsin Deficiency.
Subject has antibodies against alpha-1 proteinase inhibitor
Subject has renal, liver or multisystem organ failure
Subject has known history of hypersensitivity following infusions of human blood or blood components (eg, human immunoglobulins or human albumin).
Positive serological test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Humam Farah, MD
Organizational Affiliation
Employee
Official's Role
Principal Investigator
Facility Information:
Facility Name
Blessing Corporate Services, Inc
City
Hannibal
State/Province
Missouri
ZIP/Postal Code
63401
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Aralast NP With Antiviral Treatment and Standard of Care Versus Antiviral Treatment With Standard of Care in Hospitalized Patients With Pneumonia and COVID-19 Infection
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