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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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ClinicalTrials.gov Identifier: NCT04675086
Recruitment Status : Withdrawn (Administrative Decision)
First Posted : December 19, 2020
Last Update Posted : December 21, 2020
Sponsor:
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
Blessing Corporate Services, Inc

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.

Condition or disease Intervention/treatment Phase
Covid19 Pneumonia, Viral Drug: alpha1-proteinase inhibitor Drug: Antiviral Agents Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Aralast NP + Antiviral Treatment + Standard of Care

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.

Drug: alpha1-proteinase inhibitor
Alpha1-Proteinase Inhibitor (Human), AralastÔ, is a sterile, stable, lyophilized preparation of purified human alpha1-proteinase inhibitor (a1-PI), also known as alpha1-antitrypsin.
Other Name: Aralast NP

Drug: Antiviral Agents
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
Other Name: Remdesivir

Active Comparator: Antiviral Treatment + Standard of Care

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.

Drug: Antiviral Agents
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
Other Name: Remdesivir




Primary Outcome Measures :
  1. Duration of new non-invasive ventilation or high flow oxygen use (measured by days) [ Time Frame: 365 Days ]

Secondary Outcome Measures :
  1. Clinical status on a 7-point ordinal scale (from 1=death to 7=not hospitalized [ Time Frame: 1 Year ]
  2. The percentage change in cytokine levels from screening through day 10, Day 17 and Day 24 [ Time Frame: 10 Days, 17 Days, & 24 Days ]
  3. The percentage change in oxygen requirements including PEEP and FiO2 from screening through day 10. [ Time Frame: 10 Days ]
  4. The percentage of subjects that required mechanical ventilation during the treatment period. [ Time Frame: 1 Year ]
  5. The percent of patients with a SOFA score between 0-6 during treatment period. [ Time Frame: 1 Year ]
  6. The percent of mortality during the treatment period. [ Time Frame: 1 Year ]
  7. Evaluate the need, dosage and duration of vasopressors (number of days and average daily dose). [ Time Frame: 1 Year ]
  8. Number of Days fever free (defined by temperature of <100°F (oral) for 24 hours) [ Time Frame: 1 Year ]
  9. To evaluate the average number of days in the ICU [ Time Frame: 1 Year ]
  10. To evaluate the average number of days in the hospital [ Time Frame: 1 Year ]
  11. To evaluate the number of days with a PO2/FiO2 <300 or other parameters decided on with oxygen [ Time Frame: 1 Year ]
  12. The risk of coagulopathy by measuring Prothrombin time & Partial Thromboplastin time [ Time Frame: 1 Year ]
  13. The risk of coagulopathy by measuring D-Dimer [ Time Frame: 1 Year ]
  14. The risk of coagulopathy by measuring Platelet Counts [ Time Frame: 1 Year ]

Other Outcome Measures:
  1. 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 ]
  2. Maximal inspiratory pressure (MIP) at Day 10, Day 17 and Day 24. [ Time Frame: 10 Days, 17 Days, & 24 Days ]
  3. Maximal expiratory pressure (MEP) at Day 10, Day 17, and Day 24. [ Time Frame: 10 Days, 17 Days, & 24 Days ]
  4. Muscle strength assessment at Day 10, Day 17 and Day 24. [ Time Frame: 10 Days, 17 Days, & 24 Days ]
  5. Correlation between plasma exposure of Aralast NP (Pharmacokinetics) and the other listed clinical endpoints at Days 1, 3, 5, 7, 9 and 17. [ Time Frame: 1 Day, 3 Days, 5 Days, 7 Days, 9 Days, & 17 Days ]
    Pharmacokinetics of Aralast NP levels will be drawn to determine if there is a correlation between that and the other endpoints listed above.

  6. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. Subject will sign and date an informed consent form.
  2. Hospitalized subjects will be 18 years of age or older.
  3. Lab confirmed positive for COVID-19 within 72 hours prior to randomization.
  4. 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.
  5. 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

  1. Subject is on mechanical ventilation at time of screening.
  2. Subject is not expected to survive greater than 48 hours from screening based on PI judgement.
  3. Prior or current treatment with anti-IL-6, anti-IL-6 R antagonist or JAK inhibitors.
  4. Subject is on immunosuppressive agents, with the exception of corticosteroids for severe COVID-19 patients at the discretion of the PI.
  5. Subject is currently participating in a trial for any other investigational drug.
  6. Subject is on another plasma derived product or has received plasma or blood products within the last 48 hours.
  7. Subject is pregnant or breastfeeding.
  8. The subject, or the next of kin/power of attorney are not able to give the proper informed consent.
  9. The subject has a known IgA deficiency with anti-IgA antibodies.
  10. Subject has a known Alpha-1 Antitrypsin Deficiency.
  11. Subject has antibodies against alpha-1 proteinase inhibitor
  12. Subject has renal, liver or multisystem organ failure
  13. Subject has known history of hypersensitivity following infusions of human blood or blood components (eg, human immunoglobulins or human albumin).
  14. Positive serological test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.

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): NCT04675086


Locations
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United States, Missouri
Blessing Corporate Services, Inc
Hannibal, Missouri, United States, 63401
Sponsors and Collaborators
Blessing Corporate Services, Inc
Takeda Pharmaceuticals North America, Inc.
Investigators
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Principal Investigator: Humam Farah, MD Employee
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Responsible Party: Blessing Corporate Services, Inc
ClinicalTrials.gov Identifier: NCT04675086    
Other Study ID Numbers: CCR-2020-103188
First Posted: December 19, 2020    Key Record Dates
Last Update Posted: December 21, 2020
Last Verified: December 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
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Pneumonia, Viral
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases
Antiviral Agents
Protease Inhibitors
Alpha 1-Antitrypsin
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors
Serine Proteinase Inhibitors