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

NCT04675086 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: CCR-2020-103188
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19; Pneumonia, Viral

Outcome Measures

Primary Outcomes (1)

• Duration of new non-invasive ventilation or high flow oxygen use (measured by days)

  365 Days

Secondary Outcomes (14)

• Clinical status on a 7-point ordinal scale (from 1=death to 7=not hospitalized

  1 Year

• The percentage change in cytokine levels from screening through day 10, Day 17 and Day 24

  10 Days, 17 Days, & 24 Days

• The percentage change in oxygen requirements including PEEP and FiO2 from screening through day 10.

  10 Days

• The percentage of subjects that required mechanical ventilation during the treatment period.

  1 Year

• The percent of patients with a SOFA score between 0-6 during treatment period.

  1 Year

Other Outcomes (6)

• The percentage of patients with lung fibrosis or worsening of lung fibrosis from screening to Day 10 and Day 24 (as assessed by CT).

  10 Days, 17 Days, & 24 Days

• Maximal inspiratory pressure (MIP) at Day 10, Day 17 and Day 24.

  10 Days, 17 Days, & 24 Days

• Maximal expiratory pressure (MEP) at Day 10, Day 17, and Day 24.

  10 Days, 17 Days, & 24 Days

Study Arms (2)

Aralast NP + Antiviral Treatment + Standard of Care

EXPERIMENTAL

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; Drug: Antiviral Agents

Antiviral Treatment + Standard of Care

ACTIVE COMPARATOR

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

Interventions

alpha1-proteinase inhibitor DRUG

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

Also known as: Aralast NP

Aralast NP + Antiviral Treatment + Standard of Care

Antiviral Agents DRUG

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

Also known as: Remdesivir

Antiviral Treatment + Standard of Care; Aralast NP + Antiviral Treatment + Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Blessing Corporate Services, Inc: lead
• Takeda Pharmaceuticals North America, Inc.: collaborator

Study Sites (1)

Blessing Corporate Services, Inc

Hannibal, Missouri, 63401, United States

Location

MeSH Terms

Conditions

COVID-19; Pneumonia, Viral

Interventions

alpha 1-Antitrypsin; Antiviral Agents; remdesivir

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Humam Farah, MD

  Employee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 19, 2020
• Study Start: January 1, 2021
• Primary Completion: September 1, 2021
• Study Completion: December 1, 2021
• Last Updated: December 21, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)