A Study to Evaluate Safety and Efficacy of Convalescent Methylene Blue Treated (MBT) Plasma From Donors Recovered From Coronavirus Disease 2019 (COVID-19)

A Multicenter, Randomized, Open-label, Parallel Group Pilot Study to Evaluate Safety and Efficacy of Convalescent Methylene Blue Treated (MBT) Plasma From Donors Recovered From Coronavirus Disease 2019 (COVID-19) With Standard Medical Treatment (SMT) Versus SMT Alone in Subjects With COVID-19 Requiring Admission to the Intensive Care Unit (ICU)

The purpose of the study is to determine if Convalescent anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Methylene Blue Treated (MBT) plasma plus Standard Medical Treatment (SMT) can reduce all-cause mortality versus SMT alone in hospitalized participants with COVID-19 requiring admission to the intensive care unit (ICU) through Day 29.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: Convalescent anti-SARS-CoV-2 MBT Plasma; Drug: Standard Medical Treatment

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain
    • Hospital General Universitario de Alicante
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Girona, Spain
    • Hospital Universitari de Girona Doctor Josep Trueta
  • L'Hospitalet De Llobregat, Spain
    • Hospital Universitari de Bellvitge
  • Lleida, Spain
    • Hospital Universitari Arnau de Vilanova
  • Madrid, Spain
    • Fundacion Jimenez Diaz
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario La Princesa
  • Santa Cruz De Tenerife, Spain
    • Complejo Hospitalario Universitario de Canarias
  • Santiago, Spain
    • Hospital Clínico Universitario de Santiago -CHUS
  • Tarragona, Spain
    • Hospital Universitari Joan XXIII

Participation Criteria

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 subjects of ≥ 18 years of age at time of Screening who are being treated in the intensive care unit (ICU) for COVID-19 for not longer than 48 hours or for whom a decision has been made that COVID-19 disease severity warrants ICU admission.
• Subject (or a legal representative or a nearest relative or a relative by marriage, as appropriate) provides informed consent (ICF) prior to initiation of any study procedures.
• 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.

• Illness (symptoms) of any duration, and the following:

  1. Radiographic infiltrates by imaging (chest x-ray, computerized tomography [CT] scan, etc.), and
  2. Requiring mechanical ventilation and/or supplemental oxygen
• Subjects with no limitation of therapeutic effort (decision on the status and future of the subject).
• 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.

Exclusion Criteria:

• Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may place the subject at undue medical risk.
• The subject has had a known serious anaphylactic reaction to blood, any blood-derived or plasma product or methylene blue.
• A medical condition in which the infusion of additional fluid is contraindicated.
• Shock unresponsive to fluid challenge and/or multiple vasopressors and accompanied by multiorgan failure considered by the Principal Investigator not able to be reversed.

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: Convalescent anti-SARS-CoV-2 MBT Plasma + SMT; Participants will receive 2 consecutive transfusions of 200 to 250 milliliters (ml) of ABO-compatible convalescent plasma with each unit of plasma, obtained from the same convalescent donor, which will be administered on Day 1 using standard procedures for administration of fresh frozen plasma. Participants weighing less than 45 kilograms (kg) will receive two transfusions of 10 ml of convalescent plasma per kilogram of body weight with each unit of plasma obtained from the same convalescent donor. Participants will also receive all standard of care interventions while hospitalized, from Day 1 to Day 29.	Biological: Convalescent anti-SARS-CoV-2 MBT Plasma; Intravenous infusion.; Drug: Standard Medical Treatment; SMT
Active Comparator: Standard Medical Treatment; Participants will receive all standard of care interventions required throughout the participant's hospitalization, from Day 1 to Day 29.	Drug: Standard Medical Treatment; SMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All-Cause Mortality Rate	Up to Day 29

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in National Early Warning Score (NEWS)	Day 1 through Day 29
Time to Clinical Response as Assessed by NEWS ≤ 2 Maintained for 24 hours	Day 1 through Day 29
Time to Hospital Discharge	Day 1 through Day 29
Time to ICU Discharge	Day 1 through Day 29
Duration of All Oxygen Use	Day 1 through Day 29
Duration of Mechanical Ventilation	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
Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale	Day 15 and Day 29

Collaborators and Investigators

• Sponsor: Instituto Grifols, S.A.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2020
• Primary Completion (Actual): February 4, 2021
• Study Completion (Actual): February 4, 2021

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 3, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 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: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: GC2003; 2020-001299-14 (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