Study to Evaluate the Safety and Efficacy of Prolastin in Hospitalized Subjects With COVID-19

A Multicenter, Randomized, Open-label, Parallel Group Pilot Study to Evaluate the Safety and Efficacy of Prolastin Plus Standard Medical Treatment (SMT) Versus SMT Alone in Hospitalized Subjects With COVID-19

The primary objective of the study is to determine if Prolastin plus SMT can reduce the proportion of subjects dying or requiring intensive care unit (ICU) admission on or before Day 15 or who are dependent on invasive mechanical ventilation on Day 15 versus SMT alone in hospitalized subjects with Coronavirus disease 2019 (COVID-19).

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: Prolastin; Drug: Standard Medical Treatment

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Badalona, Spain
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain
    • Hospital Clinic de Barcelona
  • Barcelona, Spain
    • Hospital Universitario Valle de Hebron
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital General Gregorio Marañón
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • Hospital Universitario Infanta Leonor
  • Madrid, Spain
    • Hospital Universitario Príncipe de Asturias
  • Castilla León
    • Burgos, Castilla León, Spain, 09006
      • Hospital Universitario de Burgos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Hospitalized male or female subject ≥ 18 years of age at the 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 in any specimen during the current hospital admission prior to randomization.

3. COVID-19 illness (symptoms) of any duration, including both of the following:

   1. Radiographic infiltrates by imaging (chest X-Ray, computerized tomography (CT) scan, etc.) and/or clinical assessment (evidence of rales/crackles on the exam) with peripheral oxygen saturation by pulse oximetry (SpO2) <94% on room air
   2. 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. Subjects provides informed consent prior to the initiation of any study procedures.

Exclusion Criteria:

1. Subjects requiring invasive mechanical ventilation or ICU admission or with PaO2/FIO2 ≤ 150 mm Hg (ie, arterial oxygen in mm Hg divided by fraction inspired oxygen concentration [eg, 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 subjects have 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.
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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolastin 120 mg/kg + Standard Medical Treatment; Subjects will receive Prolastin, two intravenous infusion (IV) doses of 120 milligram per kilogram (mg/kg), based upon the subject's body weight, on Day 1 and Day 8. Subjects will also receive all standard of care interventions while hospitalized, from Day 1 to Day 29.	Biological: Prolastin; Intravenous infusion 120 mg/kg; Other Names: Alpha1-proteinase inhibitor; Drug: Standard Medical Treatment; Standard medical treatment per local policies or guidelines; Other Names: SMT
Active Comparator: Standard Medical Treatment; Subjects will receive all standard of care interventions while hospitalized, from Day 1 to Day 29.	Drug: Standard Medical Treatment; Standard medical treatment per local policies or guidelines; Other Names: SMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Subjects Dying or Requiring ICU Admission	Up to Day 15
Percentage of Subjects Who are Dependent on Invasive Mechanical Ventilation	Day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in National Early Warning Score (NEWS)	Day 1 through Day 29
Time to Hospital Discharge	Day 1 through Day 29
Absolute Value Change from Baseline in Ordinal Scale	Day 1 through Day 29
Mean Change from Baseline in Ordinal Scale	Day 1 through Day 29
Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours	Day 1 through Day 29
Duration of ICU Stay	Up to Day 29
Duration of Any Oxygen Use	Day 1 through Day 29
Duration of Mechanical Ventilation	Up to Day 29
Percentage of Subjects in Each Severity Category of the 7-Point Ordinal Scale	Day 15, Day 29
Time to Sustained Normalization of Temperature	Day 1 through Day 29
Percentage of Subjects who Sustained Normalization of Temperature	Day 1 through Day 29
Number of Subjects who Develop Acute Respiratory Distress Syndrome (ARDS)	Up to Day 29
Length of Time to Clinical Progression	Up to Day 29
Mortality Through Day 29	Up to Day 29

Collaborators and Investigators

• Sponsor: Instituto Grifols, S.A.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Actual): April 26, 2021
• Study Completion (Actual): June 10, 2021

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: July 30, 2020
• First Posted (Actual): July 31, 2020

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 7, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Coronavirus disease
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Protease Inhibitors; Alpha 1-Antitrypsin
• Other Study ID Numbers: GC2005; 2020-001953-36 (EudraCT Number)

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No