A Randomized Open-Label Trial of CONvalenscent Plasma for Hospitalized Adults With Acute COVID-19 Respiratory Illness (CONCOR-1)
Phase: PHASE3
Conditions: COVID-19
Sponsor: Hamilton Health Sciences Corporation

 
Study Protocol 
A Randomized Open-Label Trial of CONvalescent Plasma for 
Hospitalized Adults With Acute COVID-19 Respiratory Illness  
(CONCOR-1) 
 
Version 8.0, 15 January 2021 
 
Clinicaltrials.gov registration #: NCT04348656 

 
 
  
A Randomized Open-Label Trial of CONvalescent Plasma for Hospitalized Adults 
With Acute COVID-19 Respiratory Illness (CONCOR-1) 
 
 
 
 
Co-Lead Principal-Investigators: 
Dr. Philippe Bégin and Dr. Donald Arnold 
 
 
 
 
 
 
 
U.S. Principal Investigator:   
Dr. Marshall Glesby 
 
Brazil Principal Investigator:              Dr. Luiz Amorim Filho  
 
Israel Principal Investigator:  
Dr. Martin Ellis 
 
Sponsor:  
 
Hamilton Health Sciences 
 
Country Specific Regulatory 
Weill Cornell Medical College (United States Only) 
Sponsors/Sponsor  
Fundação Pró-Instituto de Hematologia/Fundarj (Brazil 
Representatives: 
only)  
 
 
 
 
 
Meir Medical Center (Israel only) 
 
Investigational product:  
 
COVID-19 Convalescent Plasma 
 
 
 
Protocol #: 
 
 
 
GRAAL-2020-01 
 
Version and Date of Protocol:  
Version 8.0, 15 January 2021  
 
 
 
 
The study will be conducted according to the protocol and in compliance with Good Clinical 
Practice (GCP), with the Declaration of Helsinki and with other applicable regulatory 
requirements.  
 
 
 
 
This document contains confidential information.  
Do not copy or distribute without written permission from the Sponsor.  
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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CONFIDENTIAL 
 
 
 
 
 
SIGNATURE PAGE 
 
Declaration of Sponsor or Responsible Medical Officers 
 
 
Title: A Randomized Open-Label Trial of CONvalescent Plasma for Hospitalized Adults With 
Acute COVID-19 Respiratory Illness (CONCOR-1) 
 
 
 
 
 
 
 
This study protocol was subjected to critical review. The information it contains is consistent with 
current knowledge of the risks and benefits of the investigational product, as well as with the 
moral, ethical, and scientific principles governing clinical research as set out in the Declaration of 
Helsinki [2013] (APPENDIX 1), and the guidelines on Good Clinical Practice. 
 
 
 
 
 
 
 
 
 
 
_______________________________ 
              _______________________________ 
Philippe Bégin, MD, PhD, FRCPC 
 
              Donald Arnold MD, FRCPC 
 
________________________________                         _______________________________ 
Date                                                                            
  Date 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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DECLARATION OF THE SITE INVESTIGATOR 
 
Title: A Randomized Open-Label Trial of CONvalescent Plasma for Hospitalized 
Adults With Acute COVID-19 Respiratory Illness (CONCOR-1) 
 
 
 
I have read, understood and agree to abide by all the conditions and instructions 
contained in this protocol. 
 
All documentation for this study that is supplied to me and that has not been previously 
published will be kept in the strictest confidence. This documentation includes this study 
protocol, product monograph, electronic case report form (CRF), and other scientific data. 
 
The study will not be commenced without the prior written approval of a properly 
constituted Research Ethics Board (REB), Institutional Review Board (IRB) or Independent 
Ethics Committee (IEC). No changes will be made to the study protocol without the prior 
written approval of the Sponsor and the REB, IRB or IEC, except where necessary to 
eliminate an immediate hazard to the subjects. 
 
 
Responsible Investigator of the local study centre  
 
 
_____________________________________               _____________________  
Signature                                                                               Date  
 
_____________________________________  
Name (block letters)  
 
_____________________________________  
Title (block letters)  
 
_____________________________________  
Institution (block letters) 
 
 _____________________________________  
Phone number 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
4 
PROTOCOL SYNOPSIS 
Title: A Randomized, Open-Label Trial of CONvalescent Plasma for Hospitalized 
Adults With Acute COVID-19 Respiratory Illness (CONCOR-1) 
 
Development Phase:  
Phase 3   
 
Sponsor: 
Hamilton Health Sciences  
 
Study Centers:  
Centre Hospitalier Universitaire Sainte-Justine (CHUSJ), Montreal 
(Québec Coordinating Centre); McMaster Centre for Transfusion 
Research, McMaster University, Hamilton (Methods Centre); 
University of Toronto Quality in Utilization, Education and Safety in 
Transfusion (QUEST) Research Program (Logistics Centre); Weill 
Cornell Medicine/New York-Presbyterian (New York Coordinating 
Centre); Hemorio (Brazilian Coordinating Centre); Meir Medical 
Center, Kfar Saba, Israel (Israeli Centre) 
 
Participating Sites 
Approximately 40-60 centres across Canada,one Institution in the 
United States, approximately 7 centres in Brazil and one in Israel have 
agreed to participate 
 
Objective:                         
To determine the effect of COVID-19 Convalescent Plasma at 
reducing the risk of intubation or death at Day 30 in adult patients 
hospitalized for COVID-19 respiratory illness.  
 
Investigational product:    
Convalescent plasma from patients who have recovered from COVID-
19. 
 
Control: 
Standard of care 
 
Population: 
Patients ≥16 years of age (>18 years of age in the United States, 
Brazil, and Israel), who admitted for COVID-19 respiratory illness and 
receiving supplemental oxygen for whom there is ABO-compatible 
COVID-19 Convalescent Plasma available.  Patients are excluded if: 1) 
COVID-19 respiratory signs or symptoms began more than 12 days 
before randomization; 2) Currently intubated or a plan for intubation 
is in place; 3) Plasma is contraindicated (e.g. history of anaphylaxis 
from transfusion); 4) Decision in place for no active treatment. 
 
Design:                                    Multicentre randomized open-label trial comparing COVID-19 
Convalescent Plasma vs. standard of care. 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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Sample size:                     
1200 patients  
 
 
Randomization:              
2:1 Randomization (COVID-19 Convalescent Plasma to standard of 
care) stratified by centre and age (<60 years and ≥60 years). Web 
accessed randomization with variable block sizes to ensure 
concealment.  
 
Intervention: 
COVID-19 Convalescent Plasma: one unit of approximately 500 mL 
apheresis plasma collected from a single donor, or 2 units of 
approximately 250 mL collected from one or two donors who have 
recovered from C19 infection. 
 
Control Arm: standard of care  
 
Blinding: 
                         Unblinded 
 
Primary outcome:             
Intubation or death at Day 30      
 
Secondary outcomes:   
1. Time to intubation or death  
  
2. Ventilator-free days  
3. In-hospital death by Day 90 (at Day 90) 
4. Time to in-hospital death  
5. Death by Day 30 
6. Length of stay in intensive care unit (ICU)  
7. Length of stay in hospital  
8. Need for extracorporeal membrane oxygenation (ECMO) 
9. Need for renal replacement therapy 
10. Myocarditis 
11. Patient-reported outcome at Day 30 
12. Incremental cost per quality-adjusted life year (QALY)  
13. CCP transfusion-associated adverse events (AE) 
14. Grade 3 and 4 serious adverse events (SAE)  
15. Cumulative incidence of Grade 3 and 4 SAEs  
 
Primary  Analysis:    
Based on a 2-sided Wald test of the null hypothesis that intubation or 
death at Day 30 is the same among individuals receiving COVID-19 
Convalescent Plasma or standard of care (relative risk and 95% 
confidence intervals will be presented). 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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Interim Analysis: Performed when information on intubation or 
death at Day 30 is available for 50% of the target sample using an 
O'Brien-Fleming stopping rule. Blinded sample size re-estimation will 
be done at that time. 
 
Summary of Distribution of Protocol Versions: 
Version 
3.0 
Version 
4.0 
Version 
5.0 
Version 
6.0 
Version 
7.0 
Version 7.1 
Version 8.0 
Canada 
X 
  
X 
X 
  
  
X 
USA 
  
X 
X 
X 
  
  
X 
Brazil 
  
  
  
  
X 
X 
X 
Israel 
  
  
  
  
X 
 
X 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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KEY ROLES 
 
Sponsor 
 
 
 
Hamilton Health Sciences 
 
 
 
 
 
1200 Main St W 
 
 
 
 
 
Hamilton, ON L8N 3Z5 
 
Country Specific Regulatory  
Weill Cornell Medical College 
Sponsors/Sponsor 
 
 
1300 York Avenue 
Representatives: 
 
 
New York, NY 10065 
 
 
 
 
 
(United States Only) 
 
 
 
 
 
 
Fundação Pró-Instituto de Hematologia/Fundarj 
 
 
 
 
 
8 Frei Caneca Street 
                                              
             Rio de Janeiro, RJ 20211-030 
 
 
 
 
 
(Brazil only) 
 
Meir Medical Centre 
 
 
 
 
 
59 Tchernichovsky St 
 
 
 
 
 
Kfar Saba 44281, ISRAEL 
 
 
 
 
 
(Isreal only) 
 
 
 
 
 
 
 
Central Methods Centre 
 
McMaster Center for Transfusion Research 
McMaster University 
1280 Main Street West, HSC-3H50 
Hamilton, ON L8S 4K1  
 
Logistics Center 
University of Toronto Quality in Utilization, Education and 
Safety in Transfusion (QUEST) Research Program 
Sunnybrook Health Sciences Centre 
 
 
 
 
 
2075 Bayview Ave, B204 
Toronto, ON M4N 3M5 
 
Québec Co-ordinating Centre 
Centre Hospitalier Universitaire Sainte-Justine 
 
 
 
 
 
3175 Côte-Ste-Catherine,  
Montreal, QC H3T 1C5 
 
US Co-ordinating Centre 
 
Weill Cornell Medical College 
 
 
 
 
 
1300 York Avenue  
New York, NY 10065 
 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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Brazil Co-ordinating Centre             Hemorio 
 
 
 
 
 
8 Frei Caneca Street 
                                              
             Rio de Janeiro, RJ 20211-030 
 
Israel Centre:  
 
 
Meir Medical Centre 
 
 
 
 
 
59 Tchernichovsky St 
 
 
 
 
 
Kfar Saba 44281, ISRAEL 
 
 
Investigational Product Supply  
Héma-Québec (Québec) 
 
 
 
 
 
4045, Boulevard de la Côte-Vertu, 
Saint-Laurent, QC H4R 2W7 
 
Investigational Product Supply 
Canadian Blood Services (Rest of Canada) 
1800 Alta Vista Drive 
Ottawa, ON K1G 4J5 
 
Investigational Product Supply 
New York Blood Center (New York, USA) 
310 E 67th St 
New York, NY 10065 
 
Investigational Product Supply 
Hemorio (Brazil) 
 
 
 
 
 
8 Frei Caneca Street 
                                                   
Rio de Janeiro, RJ 20211-030 
 
Investigational Product Supply 
Magen David Adom (Israel) 
 
 
 
 
 
National Blood Services 
                                                   
Tel Hashomer, ISRAEL 
 
 
Co-principal investigators 
 
Donald Arnold, MD, MSc 
                                           
Hematologist, McMaster University 
 
Philippe Bégin, MD, PhD 
Clinical immunologist, CHUSJ and CHUM  
Jeannie Callum, MD 
Hematologist, University of Toronto 
Steering Committee  
 
See Appendix 2 
 
Registration:  
 
 
Clinicaltrials.gov – NCT04348656 
 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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TABLE OF CONTENTS  
 
 
DECLARATION OF THE SITE INVESTIGATOR ..................................................................................... 3 
PROTOCOL SYNOPSIS ....................................................................................................................... 4 
TABLE OF CONTENTS ........................................................................................................................ 9 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................................. 14 
 
INTRODUCTION ...................................................................................................................... 16 
1.
 
Immunologic response to  SARS-CoV-2 .......................................................................................... 16 
1.1.
 
Passive immunization ..................................................................................................................... 17 
1.2.
 
Experience with the use of convalescent plasma against other coronavirus diseases .................. 17 
1.3.
 
Experience with the use of convalescent plasma in COVID-19 ...................................................... 18 
1.4.
 
Known potential risks...................................................................................................................... 18 
1.5.
 
Known potential benefits ................................................................................................................ 19 
1.6.
 
Optimal timing ................................................................................................................................ 19 
1.7.
 
Optimal dosage ............................................................................................................................... 20 
1.8.
 
STUDY OBJECTIVES ................................................................................................................. 21 
2.
 
Primary objective: ........................................................................................................................... 21 
2.1.
 
Secondary objectives ...................................................................................................................... 21 
2.2.
 
OVERALL DESIGN AND PLAN OF THE STUDY .......................................................................... 22 
3.
 
Overview ......................................................................................................................................... 22 
3.1.
 
STUDY POPULATION ............................................................................................................... 24 
4.
 
Eligibility Criteria ............................................................................................................................. 24 
4.1.
 
Inclusion Criteria .......................................................................................................... 24 
4.1.1.
 
Exclusion Criteria .......................................................................................................... 24 
4.1.2.
 
Participant recruitment .................................................................................................................. 24 
4.2.
 
Randomization Procedures ............................................................................................................. 25 
4.3.
 
Intervention: ................................................................................................................................... 25 
4.4.
 
CCP ................................................................................................................................ 25 
4.4.1.
 
Standard of Care ........................................................................................................... 25 
4.4.2.
 
Participant Withdrawal and Discontinuation of IP ......................................................................... 26 
4.5.
 
Data Collection and Follow-up for Withdrawn Participants ........................................ 26 
4.5.1.
 
Blinding and Unblinding Procedures .............................................................................................. 26 
4.6.
 
Number of Study Centers ............................................................................................................... 26 
4.7.

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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Subject Identification and Randomization ...................................................................................... 27 
4.8.
 
Subject Identification ................................................................................................... 27 
4.8.1.
 
Interim Analysis ............................................................................................................................... 27 
4.9.
 
INVESTIGATIONAL TREATMENT ............................................................................................. 28 
5.
 
Identity ............................................................................................................................................ 28 
5.1.
 
Mechanism of action ...................................................................................................................... 28 
5.2.
 
Approved indication ........................................................................................................................ 28 
5.3.
 
Approved Indications for Canada and Israel ................................................................ 28 
5.3.1.
 
Approved Indications for the United States and Brazil ................................................ 28 
5.3.2.
 
Acquisition, Formulation and Packaging......................................................................................... 29 
5.4.
 
Donor recruitment ....................................................................................................... 29 
5.4.1.
 
Acquisition and Formulation ........................................................................................ 31 
5.4.2.
 
Packaging, Labeling and Storage ..................................................................................................... 34 
5.5.
 
For Canadian Sites: ....................................................................................................... 34 
5.5.1.
 
For United States Sites: ................................................................................................ 34 
5.5.2.
 
For Brazilian sites: ........................................................................................................ 35 
5.5.3.
 
For the Israeli site: ........................................................................................................ 35 
5.5.4.
 
Anti-SARS-CoV-2 seropositivity ....................................................................................................... 36 
5.6.
 
ELISA or Chemoluminescence ...................................................................................... 36 
5.6.1.
 
Functional assays .......................................................................................................... 36 
5.6.2.
 
Administration ................................................................................................................................ 37 
5.7.
 
Dose of CCP ..................................................................................................................................... 37 
5.8.
 
Return and/or Destruction of Investigational Product ................................................................... 37 
5.9.
 
Blinding and Breaking the Blind ...................................................................................................... 38 
5.10.
 
Investigational Product Accountability ........................................................................................... 38 
5.11.
 
Compliance ..................................................................................................................................... 38 
5.12.
 
Prior and Concomitant Medication ................................................................................................ 38 
5.13.
 
STUDY OUTCOMES ................................................................................................................. 39 
6.
 
Primary Outcome: ........................................................................................................................... 39 
6.1.
 
Secondary Outcomes: ..................................................................................................................... 39 
6.2.
 
DURATION OF FOLLOW-UP .................................................................................................... 39 
7.
 
DATA COLLECTION AND SCHEDULE OF EVENTS .................................................................... 40 
8.
 
Data to be collected from the blood supplier................................................................................. 40 
8.1.

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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Subject Screening ............................................................................................................................ 40 
8.2.
 
Collection of daily hospital data ..................................................................................................... 40 
8.3.
 
Baseline/Enrollment (Study Day 1) ................................................................................................. 42 
8.4.
 
Collection of daily hospital data (Study Day 2 until discharge, death or Day 30 post 
8.5.
randomization). ............................................................................................................................................. 42 
 
Laboratory Test Results .................................................................................................................. 43 
8.6.
 
Discharge ......................................................................................................................................... 43 
8.7.
 
Day 30 ............................................................................................................................................. 43 
8.8.
 
Day 90 follow-up ............................................................................................................................. 43 
8.9.
 
Protocol Deviations ......................................................................................................................... 44 
8.10.
 
SAFETY VARIABLES ................................................................................................................. 45 
9.
 
Adverse Event ................................................................................................................................. 45 
9.1.
 
Serious Adverse Event .................................................................................................................... 45 
9.2.
 
Severity of Adverse Events ............................................................................................................. 46 
9.3.
 
Causality of Adverse Event .............................................................................................................. 46 
9.4.
 
Relation to investigational product .............................................................................. 46 
9.4.1.
 
Recording Adverse Events occurring after the end of the study .................................................... 48 
9.5.
 
Adverse Event Reporting ................................................................................................................ 48 
9.6.
 
Serious Adverse Event Reporting ................................................................................. 48 
9.6.1.
 
Sponsor Reporting of SUSARs: Notifying Health Canada ............................................. 49 
9.6.2.
 
Reporting of Serious Adverse Events to the FDA ......................................................... 49 
9.6.3.
 
Reporting of Serious Adverse Events to Agência Nacional de Vigilância Sanitária 
9.6.4.
(ANVISA-Brazil) ........................................................................................................................... 50 
 
Reporting of Serious Adverse Events to the Meir Medical Centre Ethics Committee 
9.6.5.
and Israeli Ministry of Health ..................................................................................................... 50 
 
Sponsor Reporting of SUSARs: Notifying Sites ............................................................. 50 
9.6.6.
 
Type and Duration of Follow-up for Adverse Events ...................................................................... 50 
9.7.
 
Reporting and Entry Timelines ........................................................................................................ 50 
9.8.
 
Reporting of Events Other than Serious Adverse Event ................................................................. 51 
9.9.
 
Adverse Events to Convalescent Plasma Transfusion .................................................................... 51 
9.10.
 
Pregnancy ................................................................................................................. 51 
9.10.1.
 
Treatment of Overdose of investigational product .................................................. 52 
9.10.2.
 
INDEPENDENT COMMITTEES .............................................................................................. 52 
10.
 
Independent Data Safety Monitoring Committee .......................................................................... 52 
10.1.

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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Community Advisory Committee .................................................................................................... 53 
10.2.
 
SITE MONITORING, AUDITING AND INSPECTING ................................................................ 54 
11.
 
Informed Consent ........................................................................................................................... 54 
11.1.
 
Data Quality Assurance ................................................................................................................... 55 
11.2.
 
Database Management and Quality Control ............................................................ 55 
11.2.1.
 
Case Report Forms and Source Documentation ............................................................................. 55 
11.3.
 
Data Collection ......................................................................................................... 55 
11.3.1.
 
Access to Source Data ..................................................................................................................... 56 
11.4.
 
Remote Monitoring .................................................................................................. 56 
11.4.1.
 
Inspection and Audit Procedures ............................................................................. 56 
11.4.2.
 
Data Processing ............................................................................................................................... 57 
11.5.
 
Archiving Study Records ................................................................................................................. 57 
11.6.
 
Good Clinical Practice ..................................................................................................................... 57 
11.7.
 
Protocol Approval and Amendment ............................................................................................... 58 
11.8.
 
Duration  of the Study ..................................................................................................................... 58 
11.9.
 
Premature Termination of the Study .............................................................................................. 58 
11.10.
 
Confidentiality ................................................................................................................................. 59 
11.11.
 
Publication Policy ............................................................................................................................ 59 
11.12.
 
Critical Documents .......................................................................................................................... 60 
11.13.
 
Clinical Study Report ....................................................................................................................... 60 
11.14.
 
STATISTICAL CONSIDERATIONS ........................................................................................... 61 
12.
 
Sample Size Considerations ............................................................................................................ 61 
12.1.
 
Planned Interim Analyses ................................................................................................................ 61 
12.2.
 
Safety Review ............................................................................................................ 61 
12.2.1.
 
Efficacy Review ......................................................................................................... 61 
12.2.2.
 
Stopping Rules................................................................................................................................. 62 
12.3.
 
Final Analysis Plan ........................................................................................................................... 62 
12.4.
 
Primary Efficacy Endpoint ......................................................................................... 63 
12.4.1.
 
Secondary Endpoints ................................................................................................ 63 
12.4.2.
 
Safety Analysis .......................................................................................................... 64 
12.4.3.
 
Sub-Group Analysis ................................................................................................... 65 
12.4.4.
 
Exploratory Analysis ................................................................................................. 65 
12.4.5.
 
LIST OF APPENDICES ............................................................................................................ 66 
13.

 
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REFERENCES ........................................................................................................................ 67 
14.
APPENDIX 1 : Declaration of Helsinki ............................................................................................................ 71 
APPENDIX 2: Steering Committee ................................................................................................................. 76 
 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS  
ADE  
 
Antibody-dependent enhancement of infection 
AE  
 
Adverse Event  
AFP  
 
Apheresis Frozen Plasma 
CBS  
 
Canadian Blood Services 
CCP 
 
COVID-19 Convalescent Plasma 
CHU   
Centre Hospitalier Universitaire 
CI  
 
Confidence Interval  
CoV  
 
Coronavirus 
CRF  
 
Case report form 
ECMO   
Extracorporeal Membrane Oxygenation 
e-CRF   
Electronic Case Report Form 
EDC  
 
Electronic Data Capture  
ELISA   
Enzyme-linked immunosorbent assay  
FDA  
 
U.S. Food and Drug Administration  
GCP  
 
Good Clinical Practice  
HBV   
Hepatitis B virus  
HCV   
Hepatitis C virus  
HLA  
 
Human leukocyte antigen  
HIV  
 
Human immunodeficiency virus  
HUS   
Hemolytic Uremic Syndrome  
IRB 
 
Institutional Review Board 
ICF  
 
Informed Consent Form  
ICU  
 
Intensive Care Unit  
ICH 
  
International Conference on Harmonization  
IDSMC  
Independent Data Safety Monitoring Committee 
IEC  
 
Independent Ethics Committee  
IMP  
 
Investigational Medicinal Product 
IND 
 
Investigational New Drug 
LAR  
 
Legally Authorized Representive 
MedDRA  
Medical Dictionary for Regulatory Activities 
MERS-CoV  
Middle Eastern respiratory syndrome coronavirus 
NYBC  
New York Blood Center 
NYP 
 
NewYork-Presbyterian 
OR 
 
Odds ratio 
PCR  
 
Polymerase chain reaction  
RBD 
 
Receptor-binding domain 
REB 
 
Research Ethics Board 
RNA   
Ribonucleic acid 
RT-PCR  
Reverse transcriptase polymerase chain reaction  
SAE  
 
Serious Adverse Event  
SAP  
 
Statistical Analysis Plan  
SARS-CoV-1  Severe Acute Respiratory Syndrome Coronavirus 1 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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SARS-CoV-2  Severe Acute Respiratory Syndrome Coronavirus 2 
SpO2   
Peripheral capillary oxygen saturation  
SUSAR  
Suspected Unexpected Serious Adverse Reaction 
TACO   
Transfusion associated cardiac overload 
TRALI   
Transfusion related acute lung injury 
TTP  
 
Thrombotic Thrombocytopenic Purpura 
USA 
 
United States of America 
WCMC  
Weill Cornell Medical College 
WMA   
World Medical Association 
 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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 INTRODUCTION 
1.
Coronavirus (CoVs) are positive-sense single stranded enveloped ribonucleic acid (RNA) viruses, 
many of which are commonly found in humans and cause mild symptoms. Over the past two 
decades, emerging pathogenic CoVs capable of causing life-threatening disease in humans and 
animals have been identified, namely severe acute respiratory syndrome coronavirus (SARS-
CoV-1) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). 
 
In December 2019, the Wuhan Municipal Health Committee (Wuhan, China) identified an 
outbreak of viral pneumonia cases of unknown cause. Coronavirus RNA was quickly identified in 
some of these patients. This novel coronavirus has been abbreviated as SARS-CoV-2 and has 
89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV-11. 
Initially, most of the infections outside China were travel-associated cases in those who had 
recently visited Wuhan City and were thought to have acquired the virus through contact with 
infected animals or contact with infected people. There has subsequently been global spread 
of the virus, including local (human-to-human) spread in many countries, including Canada. 
 
This novel coronavirus has been designated SARS-CoV-2, and the disease caused by this virus has 
been designated COVID-19. Outbreak forecasting and mathematical modelling suggest that the 
number of people with COVID-19 will continue to rise in many countries over the coming weeks to 
months2.  Global efforts to evaluate novel antivirals and therapeutic strategies to treat COVID-
19 have intensified. There is an urgent public health need for rapid development of novel 
interventions. 
   
At present, there is no specific antiviral therapy for coronavirus infections. Few treatment studies 
have been conducted because most human coronavirus strains cause self-limited disease and 
management is supportive care.  
 
 Immunologic response to  SARS-CoV-2  
1.1.
Much is still unknown concerning the immune response to SARS-Cov-2 viral infection both in 
normal individuals and in those that develop severe disease. A previous study of patients with 
severe SARS-CoV-1 infection found  that recovered patients had higher and sustainable levels of 
both N protein‐specific and S glycoprotein‐specific neutralizing antibody responses compared to 
those who succumbed to the disease3. This suggests that antibody responses likely plays an 
important role in determining the ultimate disease outcome of SARS‐CoV‐infected patients. 
Immunologic senescence is also a hypothesis to explain the increased risk of complication of death 
or complication in the elderly population4.   
 
The details of how this inappropriate humoral response translates to the severe inflammatory 
phenotype observed in complicating cases are still unknown5. One hypothesis is that inefficient 
clearance of virus leads to disproportionate activation of cellular and innate immunity 
mechanisms, similar to macrophage activation syndromes seen with viral infections in patients 
suffering from hemophagocytic lymphohistiocytosis. In fact, ineffective non neutralizing antibodies 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
17 
against SARS-CoV-1 have been shown to worsen the inflammatory state by contributing to 
macrophage response activation and skewing6. 
 
Most therapies currently under investigation for COVID-19 are aimed either at neutralizing the 
virus (e.g. remdesivir) or at preventing this disproportionate inflammatory response, with ARDS 
and cytokine storm (e.g. anti-IL-6). Given the suspected link between dysfunctional humoral 
response and COVID-19 complications, passive immunization approaches with hyperimmune 
products or convalescent plasma could potentially do both and constitute a promising therapeutic 
avenue for severe COVID-19. 
 
 Passive immunization 
1.2.
Passive immunization consists in the transfer of antibodies from immunized donor to non-
immunized individual in order to transfer transient protection against an infective agent. A 
physiological example of passive immunization is the transfer of maternal IgG antibodies to the 
foetus through the placenta to confer humoral protection to newborns in the first years of life. 
Passive immunization differs from active immunization in which the patient develops their own 
immune response following contact with the infective agent or vaccine. 
 
Passive antibody therapy was used as early as the late 19th century to treat certain infectious 
diseases prior to the development of antimicrobial therapy in the 1940s7,8. Convalescent plasma 
was also used in the 2013 African Ebola epidemic. A small non-randomized study in Sierra Leone 
showed an improvement in survival with convalescent whole blood9 but another study with 
convalescent plasma showed no improvement in survival10. 
 
Experience from prior outbreaks with other coronaviruses, such as SARS-CoV-1 finds that 
convalescent plasma contains neutralizing antibodies to the relevant virus11. Viral neutralization is 
a mechanism whereby antibodies directed against viral surface antigens prevent their interaction 
with receptors on host cells and fusion of membranes of action of passive immunisation12. 
However, other mechanisms may be possible, such as antibody dependent-cellular cytotoxicity, 
phagocytosis or virolysis. The relative importance of these mechanisms in passive immunization or 
in normal defenses against SARS-CoV-2 is unknown. Importantly, studies in HIV have shown that 
results of assays testing these various functions (e.g. neutralization vs antibody-dependent 
cytoxicity) may not always correlate and may be complementary 13,14.  
 
 
 Experience with the use of convalescent plasma against other coronavirus diseases 
1.3.
In the 21st century, there were two other epidemics with coronaviruses that were associated with 
high mortality, SARS-CoV-1 in 2003 and MERS -CoV in 2012. In both outbreaks, the high mortality 
and absence of effective therapies led to the use of convalescent plasma. The largest study 
involved a cohort of 80 patients with severe SARS-CoV-1 pneumonia deteriorating despite 
methylprednisolone in Hong Kong15. The convalescent plasma dose of 4-5mL/kg was well 
tolerated in all patients and 33 (41%) were discharged from hospital by day 22 after the onset of 
symptoms. Three seriously ill patients with SARS in Taiwan were treated with 500 ml of 
convalescent plasma, which was associated with a reduction in plasma virus titer and good clinical 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
18 
outcomes16. Three patients with MERS-CoV in South Korea were treated with convalescent 
plasma, but only two of the donors had neutralizing antibody in their plasma17. The latter study 
highlights a challenge in using convalescent plasma; namely, that some people who recover from 
viral disease may not have high titers of neutralizing antibody18. Consistent with this point, an 
analysis of 99 samples of convalescent sera from patients with SARS-CoV-1 reported that 87 had 
neutralizing antibody with a geometric mean titer of 1:61 3.  
 
 Experience with the use of convalescent plasma in COVID-19 
1.4.
A non-peer-reviewed phase I study from China enrolled 10 severe patients with COVID-19 who 
received one dose of 200 mL of convalescent plasma showed a significant improvement in clinical 
symptoms and oxyhemoglobin saturation within 3 days. Also, within 7 days, all the patients 
showed different degrees of resorption of lung lesions. In seven patients, viral load became 
undetectable after transfusion. Importantly, no severe adverse reactions were observed19.  
 
 Another group from China also published their uncontrolled experience with convalescent plasma 
in 5 ventilated critically ill patients with COVID-1920. Following plasma transfusion, body 
temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and 
PAO2/FIO2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also 
decreased and became negative within 12 days of the transfusion, and SARS-CoV-2–specific 
enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers increased following 
the transfusion (range, 40-60 before and 80-320 on day 7). Acute respiratory distress syndrome 
(ARDS) resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from 
mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged 
from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days 
after transfusion. A third report from China described 4 critically ill patients including a pregnant 
woman who received convalescent plasma and recovered from their illness21. 
 
On March 25th, 2020, the United States Food and Drug Administration (FDA) approved the use of 
convalescent plasma under emergency investigational new drug category22. This has allowed 
licensed physicians to prescribe and obtain approval for this investigational product for the 
treatment of critically ill patients on very short notice. Our approach is to make this product 
available to Canadians in a Canada-wide clinical trial. In parallel, the U.S.-based sites and Brazil-
based sites will make product available for this trial under an investigational new drug (IND) 
application from their regulatory agencies.     The product is available at the Israeli site with per-
patient Ministry of Health approval. 
 
 
 Known potential risks 
1.5.
1. There is a theoretical risk of antibody-dependent enhancement of infection (ADE) whereby 
virus targeted by non-neutralizing antibodies contained in the convalescent plasma could 
facilitate entry into and activation of macrophages. This is based on experiments using 
antibodies from peptide vaccination in macaques. The available evidence from the use of 
convalescent plasma in patients with SARS-CoV-1 and MERS-CoV23 and anecdotal evidence of 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
19 
its use in 245 patients with COVID-1924, suggest this does not happen when using 
convalescent plasma, which contains high titres of polyclonal and likely neutralizing  
antibodies. 
2. Another theoretical risk is that antibody administration to those exposed to SARS-CoV-2 may 
mitigate severe disease but will modify the immune response such that those individuals 
mount attenuated immune responses, which would leave them vulnerable to subsequent re-
infection. In this regard, passive antibody administration before vaccination with respiratory 
syncytial virus was reported to attenuate humoral but not cellular immunity25. Experience 
with measles prophylaxis has been that active immunization was indeed suppressed when 
treatment was given in the first 5 days of viral incubation and completely aborted the 
infection. However, patients for whom treatment was given 5 to 7 days after the incubation 
period had attenuated disease and later developed normal long-lived immunization. This 
suggests that active immunization would not be attenuated in patients with active SARS-CoV-
2 infection. 
3. Finally, there are risks associated with any transfusion of plasma including transmission of 
blood transmitted viruses (risk <1 in 1 million for all known pathogens, e.g. HIV, HBV, HCV, 
etc.), allergic transfusion reactions, including anaphylaxis, febrile non-hemolytic transfusion 
reaction, transfusion related acute lung injury (TRALI), transfusion associated cardiac overload 
(TACO), and hemolysis should ABO incompatible plasma be administered (not permitted in 
the CONCOR-1 trial, except for centers where blood group A plasma can be transfused to 
blood group B or AB patients if AB plasma is not available provided the donor´s anti-B titers 
are lower than or equal to 1:50). Donors must fulfill all donor requirements for apheresis 
plasma donation.  
 
 Known potential benefits 
1.6.
Potential benefits of COVID-19 convalescent plasma (CCP) include improved survival, 
improvement in symptoms, decreased risk of intubation for mechanical ventilation, decreased risk 
of intensive care unit (ICU) admission, shortened hospitalization time and suppression of viral 
load. 
 
 Optimal timing  
1.7.
A general principle of passive antibody therapy is that it is more effective when used early. When 
used in prophylaxis for measles, treatment within 5 days of contact would usually lead to infection 
abortion, whereas treatment between 5 and 7 days would lead to infection attenuation26. When 
used for therapy, passive antibodies are most effective when administered shortly after the onset 
of symptoms. In the Hong Kong SARS cohort, convalescent plasma was found to be most effective 
in patients who were reverse transcriptase polymerase chain reaction (RT-PCR) positive and 
seronegative for coronavirus15. Passive antibody therapy for pneumococcal pneumonia was most 
effective when administered shortly after the onset of symptoms and there was no benefit if 
antibody administration was delayed passed the third day of disease27. With passive antibody 
therapy for SARS-CoV-1, Chen and al. found that administration of convalescent plasma before 
Day 14 of illness resulted in a higher discharge rate by day 22 compared to participants who 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
20 
received it later than Day 14. Two controlled cohort studies from the Spanish influenza pandemic 
reported efficacy only if treatment was administered within 5 days of onset of viral pneumonia 
(around day 12 of symptom onset). In the 2 studies, the risk of death was reduced [odd ratios (OR) 
for mortality = 0.60 and OR=0.31, respectively] when administered before 5 days, compared to an 
OR=1.13 and OR=0.93 when given after 5 days28,29. In a cohort of H1N1 influenza patients treated 
with convalescent plasma from 2013, the risk of death was reduced (OR = 0.14) when treatment 
was administered in the first 4 days, but the risk of death was increased when administered after 5 
days 30.  Given the natural evolution of COVID-19 which involves a slower progression of initial 
symptoms compared to influenza (Figure 1), CONCOR-1 will enrol patients who are within 12 days 
of respiratory symptom onset and not yet intubated. 
 
 
 
Figure 1 (from Bouadma et al Int Care Med 2020) describes what is known about the potential patient 
course of COVID-19 pneumonia. Plasma therapy is expected to be most effective if given before the red 
zone31. 
 
 Optimal dosage 
1.8.
The optimal dosage for passive antibody therapy is unknown. The following table presents 
dosages used in previous studies. 
 
Indication  
Dosages used 
Spanish influenza pneumonia32  
Single dose of 75 to 500mL 
Pediatric: single dose of 50mL 
SARS-CoV1 pneumonia15,16,23,33–35  
Single dose of 50 to 500ml  
Avian influenza (H5N1) pneumonia36–38  
3 doses of 200mL 
5 doses of 100mL 
Influenza A (H1N1) pneumonia39,40 
Single dose of 500mL 
Ebola infection41 
2 to 6 doses of 500mL 
COVID-1919,20 
Single dose of 200ml  

 
CONCOR-1 Protocol 15 January 2021 v8.0    
21 
Single dose of 400 ml 
Measles prophylaxis26,42  
Single dose of 15mL 
Pediatrics: 2.5 to 15mL 
Mumps prophylaxis43 
Single dose of 40mL 
 
  STUDY OBJECTIVES 
2.
 Primary objective: 
2.1.
To determine the effect of CCP for adults admitted to hospital with COVID-19 respiratory illness 
requiring supplemental oxygen on rates of death and intubation at 30 days. 
 
 Secondary objectives 
2.2.
Safety: Determine the safety of CCP. We will capture adverse events (AE) associated with the 
transfusion of CCP including suspected TRALI, and all other serious adverse events (SAE). 
 
Relevant data will be captured during the trial to provide information on the following: 
 Time to intubation or death   
 Ventilator-free days  
 In-hospital death by Day 90  
 Time to in-hospital death  
 Death by Day 30 
 Length of stay in intensive care unit (ICU)  
 Length of stay in hospital  
 Need for extracorporeal membrane oxygenation (ECMO) 
 Need for renal replacement therapy 
 Myocarditis 
 Patient-reported outcome at Day 30 
 Incremental cost per quality-adjusted life year (QALY) 
 Transfusion-associated adverse events (AE) 
 Grade 3 and 4 serious adverse events (SAE)  
 Cumulative incidence of Grade 3 and 4 SAEs  
 
Exploratory studies: To determine the association between CCP characteristics and rates of 
intubation or death in hospital at day 30 in participants receiving CCP. CCP characteristics to be 
assessed include the amount of antibodies against the SARS-CoV-2 spike protein and its receptor-
binding domain (RBD),its neutralizing function,  its Fc function and clinical characteristics of 
donors. 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
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 OVERALL DESIGN AND PLAN OF THE STUDY 
3.
 Overview 
3.1.
Research Question – Does the transfusion of CCP collected from donors who have recovered from 
COVID-19 infection and who have detectable anti-SARS-CoV-2 antibodies reduce the risk of 
intubation or death at Day 30 in adults who are admitted to hospital with COVID-19 respiratory 
illness compared to standard of care? 
  
Study Hypothesis - We hypothesize that treating hospitalized adult patients with COVID-19 
respiratory illness will reduce the risk of intubation or death at Day 30. In addition, we hypothesize 
that other outcomes will be improved including risk of ICU admission, length of stay in ICU and 
length of stay in hospital.  
 
Study Design: Multicentre open-label randomized controlled trial. An overview of the study design 
is included in the flow chart below. 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
23 
 
 
 
 
 
 
~500 mL ABO compatible CCP 
Primary Outcome:  
Intubation or death at Day 30 
Secondary Outcomes:  
1.
Time to intubation or death    
2.
Ventilator-free days  
3.
In-hospital death by Day 90 
4.
Time to in-hospital death  
5.
Death by Day 30 
6.
Length of stay in intensive care unit (ICU)  
7.
Length of stay in hospital  
8.
Need for extracorporeal membrane oxygenation (ECMO) 
9.
Need for renal replacement therapy 
10. Myocarditis 
11. Patient-reported outcome at Day 30 
12. Incremental cost per quality-adjusted life year (QALY) 
13. CCP transfusion-associated adverse events (AE) 
14. Grade 3 and 4 serious adverse events (SAE)  
15. Cumulative incidence of Grade 3 and 4 SAEs  
 
 
Consent 
obtained 
Randomize 
(
)
Inclusion: 

≥16 years of age (>18 years of age in USA,  
Brazil, and Israel) 

Admitted to hospital for COVID-19 
respiratory illness  

Receiving supplemental oxygen 

ABO compatible CCP unit is available  
Exclusion: 

Onset of signs or symptoms of COVID-19 
respiratory illness >12 days prior to 
randomization (i.e. cough, chest pain, 
dyspnea, or hypoxia) 

Intubated or plan for intubation in place 

Plasma is contraindicated (e.g. history of 
anaphylaxis from transfusion) 

Decision in place for no active treatment 
Eligible subject  
Standard of care 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
24 
 STUDY POPULATION 
4.
 Eligibility Criteria   
4.1.
 
 Inclusion Criteria   
4.1.1.
1. ≥16 years of age (≥18 years of age in the United States, Brazil,  and Israel) 
2. Admitted to hospital for confirmed COVID-19 respiratory illness  
3. Receiving supplemental oxygen 
4. 500 mL of ABO compatible CCP is available  
 
 Exclusion Criteria   
4.1.2.
1. Onset of signs or symptoms of COVID-19 respiratory illness >12 days prior to 
randomization (eg. cough, chest pain, dyspnea, or hypoxia) 
2. Intubated or plan in place for intubation 
3. Plasma is contraindicated (e.g. history of anaphylaxis from transfusion) 
4. Decision in place for no active treatment 
 
Potential patients will be approached for informed consent. After consent is obtained, a screening 
ABO blood group will be collected if not already performed during the current hospital admission.  
Co-enrolment in other trials is allowed. For patients who fail screening, we will collect only the 
reason for screen failure with no personal identifiers. 
 
Pregnant patients will not be excluded from the study if they meet eligibility criteria, except for 
sites where pregnant patients are not permitted to participate in the research as per local 
regulatory requirements. While young adults and pregnant women have been infrequently 
reported to present with complications, data from current COVID-19 wards indicate that those 
who develop severe COVID-19 pneumonia appear to have a similar risk of progression to 
intubation and critical disease than older patients. At the CHUM in Montreal, over half of COVID-
19 patients admitted to the ICU were younger than 55 years of age. From a safety standpoint, CCP 
was well tolerated in one pregnant patient in a case series reported from China21. Therefore, 
based on current eligibility criteria, the same risk/benefit considerations apply to pregnant and 
younger patients as compared to the elderly, hence the reason not to exclude them from this trial. 
 
 Participant recruitment  
4.2.
Only hospitalized COVID-19 patients are eligible so recruitment efforts will be focused on 
identifying consecutive patients admitted to hospital with acute COVID-19 infection. No other 
external recruitment efforts are planned. At each participating hospital, a process for immediately 
identifying admitted patients with COVID-19 will be established. The mechanism of alerting the 
research assistants (RA) will be determined by local site principal investigator. 
 
Patients who are confirmed to have COVID-19 infection and are admitted to hospital will be 
assessed for eligibility. Consent may be obtained verbally, given the infection control precautions 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
25 
in place for these participants, as permitted by local research ethics committees. The RA (or a 
bedside physician if deemed acceptable by local research ethics boards [REB]) will obtain consent 
from the patient or legally authorized representative (LAR) by phone or videoconference. After 
consent is obtained, the RA will confirm eligibility remotely through a review of the electronic 
medical record and discussion with the bedside physician/nurse. Informed consent will be 
obtained remotely and may use a variety of visual aids (video brochure, a visual decision board). 
Documented written consent will be obtained from the patient or LAR as soon as possible as 
required by local REBs. At the time of assessing eligibility the RA will confirm with the site storing 
CCP that an ABO-compatible CCP plasma unit is available (for certain sites, group A plasma with 
low-titer anti-B (≤1:50) is allowed to be transfused to group B or AB patients).   If 500 mL of CCP is 
available and eligibility criteria are met, the RA will randomize the patient. The RA will notify the 
blood bank of the allocation and a marker will be placed in the Laboratory Information System and 
the patient chart indicating that the patient is enrolled in the CONCOR-1 trial. For patients 
randomized to CCP, the RA will notify the bedside physician to order the study product. The CCP 
will be thawed in the blood bank, issued, and infused by the bedside nurse within 24 hours of 
randomization. 
 
 Randomization Procedures 
4.3.
Patients will be randomized in a 2:1 ratio (CCP to standard of care). Patients will be randomized 
using a secure, concealed, computer-generated, web-accessed randomization sequence. 
Randomization will be stratified by centre and age (<60 and ≥ 60 years). Within each stratum, 
variable permuted block sizes will be used. This approach will ensure that concealment of the 
treatment sequence is maintained.  
 
 Intervention:  
4.4.
Patients will be assigned to the experimental treatment (CCP) or the control (standard of care). 
 
 CCP  
4.4.1.
Patients will receive approximately 500 mL of CCP (from one single-donor unit of 500 mL or 2 units 
of 250 mL from one or two donors) collected by apheresis from donors who have recovered from 
COVID-19 and frozen (1 year expiration date from date of collection). The plasma unit will be 
thawed as per standard blood bank procedures and infused into the patient slowly over 4 hours or 
as per local procedures. When administering 2 units of 250 mL, the 2nd unit should be 
administered immediately after the first unit, and we recommend that it should be given within 12 
hours after the first unit. The patient will be monitored for adverse events as per each site’s 
policies. Details regarding the CCP are summarized in Section 5.0. 
 
 
 Standard of Care 
4.4.2.
Patients receiving standard of care will receive all medical care as per routine practices at each 
site. 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
26 
 Participant Withdrawal and Discontinuation of IP 
4.5.
Subjects in this clinical trial may discontinue the investigational product for any of the following 
reasons: 
 Subject requests to discontinue the investigational product during transfusion or to be 
removed from clinical trial activities for any reason (reason for withdrawal will be 
requested) 
 Occurrence of any medical condition or circumstance that exposes the patient to 
substantial risk and/or does not allow the patient to adhere to the requirements of the 
protocol 
 Any SAE, clinically significant AE, severe laboratory abnormality, intercurrent illness, or 
other medical condition deemed related to the investigational product that indicates to the 
Investigator that continued participation is not in the best interest of the patient (in such 
case the investigational product must be discontinued). 
 Patient fails to comply with protocol requirements or study-related procedures 
 
Unless the patient withdraws consent, those who discontinue the investigational product during 
the infusion should remain in the study and be included in the intention-to-treat population. The 
reason for participant discontinuation of investigational product should be documented in the 
case report form where known. 
 
Should the participant withdraw consent or requests discontinuation for any reason, whenever 
possible, the patient or LAR will be asked if the patient can be followed for outcome and safety 
evaluations (where permitted by the local REB). 
 
 Data Collection and Follow-up for Withdrawn Participants 
4.5.1.
Participants who withdraw from this study or who are lost to follow-up after randomization will 
not be replaced. The reason for patient discontinuation from the study will be recorded on the 
appropriate case report form. In the case of a participant’s lost to follow-up, attempts to contact 
the patient will be made and documented in the patient’s study file. 
 
 Blinding and Unblinding Procedures 
4.6.
This is an open-label trial. The decision to perform the trial unblinded was based on the following 
reasons: (1) to allow for participation of academic and non-academic hospital sites where masking 
procedures are not possible given the required short implementation timelines; (2) to avoid 
exposing patients to the risks of a standard plasma arm as the placebo has no anticipated benefit; 
(3) to avoid the need to create an inert placebo (e.g. coloured saline) including the need to mask, 
which would cause significant disruption of workflow and additional use of PPE during the 
pandemic. 
 
 Number of Study Centers 
4.7.
 The number of hospital sites across Canada will be ~40-60 sites, including sites in every Province 
and potentially every territory in both academic and community-based hospitals. There will be a 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
27 
gradual onboarding of sites starting with larger centres in Québec and Ontario where the burden 
of the pandemic is expected to be the largest.  We will use Clinical Trials Ontario (CTO), the central 
REB for Ontario sites and expedite time to first patient treated. The multi-centre ethics evaluation 
process will be similarly used in Québec. Thereafter sites will be on-boarded based on size and the 
current distribution of cases of COVID-19 to ensure the greatest access to the trial based on need.  
In addition, to enhance the rapidity of study enrollment, one New York City Institution in the U.S. 
will participate, as well as several sites in Brazil and one site in Israel.  
  
 
 Subject Identification and Randomization 
4.8.
 Subject Identification 
4.8.1.
Subjects in this study will have specific screening number. Subjects failing screening will retain 
their screening number. The screening number for each subject will be a combination of the site 
number plus a number assigned to the subject according to her/his chronological order of 
screening at that site. The screening number will be used as the subject identifier throughout the 
study. 
 
  Interim Analysis 
4.9.
A single interim analysis is planned when the primary outcome (intubation or mortality at Day 30) 
is available for 50% of the target sample. An O'Brien- Fleming stopping rule44 will be used at that 
time, but treated as a guideline, so there is minimal impact on the threshold for statistical 
significance for the final significance test of the primary outcome. 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
28 
 INVESTIGATIONAL TREATMENT 
5.
 Identity 
5.1.
The investigational product consists of approximately 500 mL Apheresis Frozen Plasma (AFP) 
collected from patients who have recovered from COVID-19.  
 
 Mechanism of action 
5.2.
Transfusion of AFP from COVID-19 convalescent patients allows the transfer of donor neutralizing 
antibodies directed against SARS-CoV-2 antigens in the recipient, thus allowing the generation of 
passive immunization. Naturally produced human antibody are polyclonal, meaning they are 
directed against a variety of different viral antigens and epitopes allowing for a general 
neutralizing effect against the virus rather than focussing on a specific target. Administration of 
CCP has been associated with rapid decrease in viral load.  It is also possible that passive 
immunization contributes to improved cell-mediated immunity by favoring the phagocytosis and 
presentation of viral antigens to host T cells.  
 
 Approved indication 
5.3.
 Approved Indications for Canada and Israel 
5.3.1.
AFP transfusions are currently indicated in Canada for the management of:  
 Bleeding patients or patients undergoing invasive procedures who require replacement of 
1.
multiple plasma coagulation factors 
 Patients with massive transfusion with clinically significant coagulation abnormalities 
2.
 Patients on warfarin who are bleeding of need to undergo an invasive procedure before 
3.
vitamin K could reverse the warfarin effect, and where prothrombin complex concentrate is 
not available or is contraindicated 
 Patients with selected coagulation factor or with rare specific plasma protein deficiencies for 
4.
which a more appropriate alternative therapy is not available  
 Preparation of reconstituted whole blood for exchange transfusion in neonate 
5.
 Patients with thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome 
6.
(HUS) undergoing plasma exchange 
 
 Approved Indications for the United States and Brazil 
5.3.2.
AFP transfusions are currently indicated in the United States for the management of: 
 Preoperative or bleeding patients who require replacement of multiple plasma coagulation 
1.
factors (eg. Liver disease, DIC). 
 Patients undergoing massive transfusion who have clinically significant coagulation 
2.
deficiencies. 
 Patients taking warfarin who are bleeding or need to undergo an invasive procedure before 
3.
vitamin K could reverse the warfarin effect or who need only transient reversal of warfarin 
effect. 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
29 
 Transfusion or plasma exchange in patients with thrombotic thrombocytopenic purpura 
4.
 Management of patients with selected coagulation factor deficiencies, congenital or acquired, 
5.
for which no specific coagulation concentrates are available. 
 Management of patients with rare specific plasma protein deficiencies, such as C1 inhibitor, 
6.
when recombinant products are unavailable. 
 
 Acquisition, Formulation and Packaging 
5.4.
For Canadian sites, the investigational product will be provided by Héma-Québec and Canadian 
Blood Services. For United States sites, the investigational product will be provided by the New York 
Blood Center (NYBC). For Brazilian sites, the investigational product will be provided by Hemorio. 
For the Israeli site the product will be provided by the Magen David Adom National Blood Services. 
 
 
 Donor recruitment 
5.4.1.
5.4.1.1. 
Donor recruitment for Canadian Sites 
Recovered COVID-19 patients will be identified as potential donors in collaboration with provincial 
public health services, local health authorities and individual co-investigators involved in the 
study. Potential donors may also be recruited following self-identification on the routine donor 
questionnaire or through social media. They will be contacted by phone and invited to participate 
in the program as potential donors. After obtaining consent and reviewing donor selection 
criteria, eligible participants will be directed to a Héma-Québec collection or Canadian Blood 
Services apheresis collection site in their area to donate. 
 
Criteria for donors: All donors will need to meet the criteria set forth in the Manuals 
of donor selection criteria in use at Héma-Québec or Canadian Blood Services. 
 
In addition, donors will require: 
 Prior diagnosis of COVID-19 documented by a PCR test at time of infection or by positive anti-
SARS-CoV-2 serology following infection 
 Male donors, or females with no pregnancy history or with negative anti-HLA antibodies 
 At least 6 days since last plasma donation 
 Provided informed consent    
 A complete resolution of symptoms at least 14 days prior to first donation. 
 
Criteria for donation are subject to change based on future revision of Health Canada guidance. 
 
5.4.1.2. 
Donor recruitment for United States Sites 
Recovered COVID-19 patients are being recruited through the New York Blood Center and Weill 
Cornell Medicine in separate protocols. Potential donors can self-refer via websites but also be 
referred by physicians or identified via the medical record system. Only donors with laboratory-
confirmed history of COVID-19 will be screened. After providing consent and reviewing FDA and 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
30 
NYBC donor eligibility criteria, donors are screened for the presences of SARS-CoV-2 virus in the 
nasopharynx if screening within 14 days of complete resolution in accordance with current FDA 
guidance. Criteria for donation are subject to change based on future revision of FDA guidance.  
Those found to be eligible will be referred to NYBC for donation. 
Criteria for donors:   
 Provision of informed consent 
 Aged 18 to 70 years.  Donors are not longer eligible after their 71st birthday. 
 Documented molecular diagnosis of SARS-CoV-2 by RT-PCR by nasopharyngeal swab, 
oropharyngeal swab, or sputum or detection of anti-SARS-CoV-2 IgG in serum. 
 Complete resolution of COVID-19 symptoms at least 14 days prior to donation  
 Not currently pregnant or pregnant within 6 weeks by self-report 
 Male donors, or females with no pregnancy history or with negative anti-HLA antibodies 
 Meets blood donor criteria specified by NYBC, which is consistent with FDA regulations. 
Donors will be allowed to donate every 7 days. The following information will be collection from 
donors: ABO group, sex, age, date of onset of symptoms (when available), date of resolution of 
symptoms (when available) and CCP collection date(s). 
Sterile segments of frozen plasma will be attached to all units consisting of at least 2 mL of plasma 
volume. These segments will be submitted to the Centre Hospitalier de l’Université de Montréal 
Research Center for testing of SARS-COV-2 antibody titer and neutralizing antibody titer. 
5.4.1.3. 
Donor recruitment for Brazil 
Recovered COVID-19 patients will be identified as potential donors in collaboration with provincial 
public health services, local health authorities, individual co-investigators involved in the study.  
Potential donors may also be recruited following self-identification on the routine donor 
questionnaire or through social media. They will be contacted by phone and invited to come to 
Hemorio in order to undergo a medical examination that will include the collection of blood 
samples. If they are approved as plasma donors, after obtaining consent, they are invited to make 
an appointment to come back  and donate plasma, as soon as possible.  
 
Criteria for donors: All donors will need to meet the criteria set forth in the Manuals 
of donor selection criteria in use at Hemorio and in Brazilian specific regulations.    
 
In addition, donors will require: 
 
 Aged 18 to 60 years. Donors are no longer eligible after their 61st birthday 
 Prior diagnosis of COVID-19 documented by a PCR test at time of infection or by positive 
anti-SARS-CoV-2 serology following infection 
 Male donors, or females with no pregnancy history or with negative anti-HLA antibodies 
 At least 7 days since last plasma donation 
 Provided informed consent   

 
CONCOR-1 Protocol 15 January 2021 v8.0    
31 
 7-day interval between each donation, limited to 4 donations over a 2 month period  
 A complete resolution of COVID-19 symptoms at least 14 days prior to first donation. 
 
Criteria for donation are subject to change based on future revision of Brazilian federal regulation.  
 
5.4.1.4. 
Donor recruitment for Israel 
Recovered COVID-19 patients will be identified as potential donors in collaboration with national 
health services, local health authorities and individual co-investigators involved in the study. 
Potential donors may also be recruited following self-identification on the routine donor 
questionnaire or through social media. They will be contacted by phone and invited to participate 
in the program as potential donors. After obtaining consent and reviewing donor selection 
criteria, eligible participants will be directed to the Magen David Adom National Blood Services 
apheresis collection site in their area to donate. 
 
Criteria for donors: All donors will need to meet the criteria set forth in the Manuals 
of donor selection criteria in use at Magen David Adom National Blood Services 
 
In addition, donors will require: 
 Prior diagnosis of COVID-19 documented by a PCR test at time of infection or by positive anti-
SARS-CoV-2 serology following infection 
 Male donors, or females with no pregnancy history or with negative anti-HLA antibodies 
 At least 14 days since last plasma donation 
 Provided informed consent    
 A complete resolution of symptoms at least 14 days prior to first donation. 
 
Criteria for donation are subject to change based on future revision of Israel Ministry of Health 
guidance. 
 
 Acquisition and Formulation 
5.4.2.
5.4.2.1. 
For Canadian Sites 
Plasma will be collected by apheresis from qualified donors who have consented to donate, using 
the equipment and technologies already in operation at Héma-Québec and Canadian Blood 
Services following standard operating procedures. 
 
Because apheresis collection allows for plasma only collection while blood cells are returned to the 
donor, donor are eligible to donate every 6 days (at minimum). This will permit the collection of 
CCP from the same donor at weekly intervals. SARS-CoV-2 antibody titers will be monitored at 
each donation to ensure the presence of sufficient amounts of antibody for the treatment of 
patients suffering from COVID-19. 
 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
32 
Plasma collection using the TRIMA® Accel™ technology (Terumo BCT) 
The TRIMA® Accel™ technology allows the automated collection of different blood components 
and contains programs for plasma collection only. Disposable sterile kits for plasma collection are 
available (kits with 3 or 4 plasma bags). Depending on the donor characteristics (calculated blood 
volume), plasma volumes up to 750 mL can be collected. The procedure starts with the collection 
of a small volume of blood in a sampling bag; this blood will be used for regulatory analyses at 
Héma-Québec and Canadian Blood Services (transfusion transmissible diseases) and to establish 
the anti-SARS-CoV-2 seropositivity. During collection, blood is mixed with ACD-A (anticoagulant 
citrate dextrose, solution A), plasma is separated from blood cells by centrifugation and collected 
in 2 or 3 bags (depending on the target volume that has been predefined) based on the estimated 
total blood volume of the donor whereas blood cells are returned to the donor.  
 
Plasma collection using the PCS®2 technology (Haemonetics) 
This automated system is used to collect plasma only. Samples required for regulatory analyses 
and antibody seropositivity determination are taken directly from the collected unit after plasma 
collection is completed. During collection, blood is mixed with anticoagulant (sodium citrate 4%) 
to avoid clotting and centrifuged in a single use, sterile centrifugation bowl to separate plasma 
from blood cells. When separation is completed, plasma is automatically transferred to the 
collection bag and thereafter, blood cells are returned to the donor.  
 
5.4.2.2. 
For United States Sites 
Plasma will be collected by apheresis from qualified donors who have consented to donate using 
the equipment and technologies already in operation at the New York Blood Center following 
standard operating procedures. Donors are eligible to donate every 7 days. This will permit 
collection of CCP from the same donor at weekly intervals.  
Plasma collection using the TRIMA® Accel™ technology (Terumo BCT) 
The TRIMA® Accel™ technology allows the automated collection of different blood components 
and contains programs for plasma collection only. Disposable sterile kits for plasma collection are 
available (kits with 3 or 4 plasma bags). Dependent on the donor characteristics (calculated blood 
volume), plasma volumes up to 750 mL can be collected. The procedure starts with the collection 
of a small volume of blood in a sampling bag; this blood will be used for regulatory analyzes at 
NYBC (transfusion transmitted disease testing). During collection, blood is mixed with ACD-A 
(anticoagulant citrate dextrose, solution A), plasma is separated from blood cells by centrifugation 
and collected in 2 or 3 bags (depending on the target volume that has been pre-defined) based on 
the estimated total blood volume of the donor whereas blood cells are returned to the donor.  
Plasma collection using the Alyx® component collection system (Fresenius Kabi) 
This automated system can be used to collect plasma only. Samples required for regulatory 
analyses are taken directly from the collected unit after plasma collection is completed. During 
collection, blood is mixed with ACD-A to avoid clotting and centrifuged in a single use, sterile 
centrifugation bowl to separate plasma from blood cells. When separation is completed, plasma is 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
33 
automatically transferred to the collection bag and thereafter, blood cells are returned to the 
donor. 
5.4.2.3. 
For Brazilian sites 
Plasma collection using the MCS®+ technology (Haemonetics) 
 
This automated system can be used to collect plasma. Samples required for regulatory analyses 
and antibody seropositivity determination are taken directly from the collected unit after plasma 
collection is completed. During collection, blood is mixed with anticoagulant (sodium citrate 4%) 
to avoid clotting and centrifuged in a single use, sterile centrifugation bowl to separate plasma 
from blood cells. When separation is completed, plasma is automatically transferred to the 
collection bag and thereafter, blood cells are returned to the donor. Depending on donor 
characteristics, plasma volumes up to 600 mL can be collected.  
 
5.4.2.4. 
For the Israeli site 
Plasma will be collected by apheresis from qualified donors who have consented to donate, using 
the equipment and technologies already in operation at Magen David Adom Nationa Blood 
Services following standard operating procedures. 
 
Because apheresis collection allows for plasma only collection while blood cells are returned to the 
donor, donor are eligible to donate every 14 days (at minimum). This will permit the collection of 
CCP from the same donor at weekly intervals. SARS-CoV-2 antibody titers will be monitored at 
each donation to ensure the presence of sufficient amounts of antibody for the treatment of 
patients suffering from COVID-19. 
 
Plasma collection using the TRIMA® Accel™ technology (Terumo BCT) 
 
The TRIMA® Accel™ technology allows the automated collection of different blood components 
and contains programs for plasma collection only. Disposable sterile kits for plasma collection are 
available (kits with 3 or 4 plasma bags). Depending on the donor characteristics (calculated blood 
volume), plasma volumes up to 750 mL can be collected. The procedure starts with the collection 
of a small volume of blood in a sampling bag; this blood will be used for regulatory analyses at 
Magen David Adom National Blood Services (transfusion transmissible diseases) and to establish 
the anti-SARS-CoV-2 seropositivity. During collection, blood is mixed with ACD-A (anticoagulant 
citrate dextrose, solution A), plasma is separated from blood cells by centrifugation and collected 
in 2 or 3 bags (depending on the target volume that has been predefined) based on the estimated 
total blood volume of the donor whereas blood cells are returned to the donor.  
 
Plasma collection using the PCS®2 technology (Haemonetics) 
 
This automated system is used to collect plasma only. Samples required for regulatory analyses 
and antibody seropositivity determination are taken directly from the collected unit after plasma 
collection is completed. During collection, blood is mixed with anticoagulant (sodium citrate 4%) 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
34 
to avoid clotting and centrifuged in a single use, sterile centrifugation bowl to separate plasma 
from blood cells. When separation is completed, plasma is automatically transferred to the 
collection bag and thereafter, blood cells are returned to the donor.  
 
 Packaging, Labeling and Storage 
5.5.
Labels bearing the ISBT 128 donation identification will be printed and placed on all collection bags 
and blood tubes before donation. After donation, plasma will be shipped to a component 
processing facility at Héma-Québec, Canadian Blood Services, or New York Blood Center and will 
be frozen at -18°C within 8-24 hours of collection. In Hemorio and in Magen David Adom National 
Blood Services the plasma will be collected at the same place where the component process 
facility is located. When results of regulatory analyses become available (this usually takes less 
than 48 hours) and the product can be released for transfusion, a new label will be applied on the 
plasma bag showing all product information including the ABO group. The plasma will also be 
labeled as “convalescent plasma” at Canadian, Brazilian, and Israeli sites and “apheresis plasma” at 
United States sites.  
 
 For Canadian Sites: 
5.5.1.
The sponsor shall ensure that the drug bears a label that sets out the following information in both 
official languages:  
(a) a statement indicating that the drug is an investigational drug to be used only by a qualified 
investigator;  
(b) the name, number or identifying mark of the drug;  
(c) the expiration date of the drug;  
(d) the recommended storage conditions for the drug;  
(e) the lot number of the drug;  
(f) the name and address of the sponsor;  
(g) the protocol code or identification. 
 
A segregated storage area will be set up and used to keep CCP apart from the other plasma 
products. A product list will be kept up to date in order to know at all times the volume of CCP 
available for each ABO blood group. When requested for transfusion, the products will be shipped 
to the hospital through the regular transportation system for blood products or to pre-identified 
regional “hub” hospitals where inventory will be maintained. Large sites and those at a 
geographical distance of more than 200 km may be permitted to hold a stock of one 500 mL dose 
for each ABO blood group and smaller sites will only be shipped the investigation product once a 
patient has been randomized to the active treatment arm. 
 
 For United States Sites: 
5.5.2.
The sponsor shall ensure that the drug bears a label that sets out the following information in 
English: 
(a) A statement indicating that the drug is a new drug limited by federal (or United States) law 
for investigational use only; 
(b) The name, number or identifying mark of the drug; 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
35 
(c) The expiration date of the drug; 
(d) The recommended storage conditions of the drug; 
(e) The donor identification number 
 
After collection, processing, and completion of donor regulatory analyses, the product will be 
shipped to the hospital blood bank for storage. A segregated storage area will be set up and used 
to keep the CCP apart from the other plasma products. A product list will be kept up to date in 
order to know at all times the number of units available and their corresponding blood volumes 
and ABO types.  
 
 For Brazilian sites: 
5.5.3.
The sponsor shall ensure that the drug bears a label that sets out the following information in both 
official languages:  
(a) a statement indicating that the drug is for research use and should only be used by a qualified 
investigator;  
(b) the name, number or identifying mark of the drug;  
(c) the expiration date of the drug;  
(d) the recommended storage conditions for the drug;  
(e) the donor identification number;  
(f) the name and address of the blood center;  
 
A segregated storage area will be set up and used to keep CCP apart from the other plasma 
products. A product list will be kept up to date in order to know at all times the volume of CCP 
available for each ABO blood group. When requested for transfusion, the products will be shipped 
to the hospital through the regular transportation system for blood products (to hospitals located 
in Rio de Janeiro area) and by plane to hospital located in other states, where inventory will be 
kept. Sites at a geographical distance of more than 200 km may be permitted to hold a stock of 
three 500 mL doses for each ABO blood group.  
 
 For the Israeli site: 
5.5.4.
The sponsor shall ensure that the drug bears a label that sets out the following information in 
Hebrew: 
(a) The name, number or identifying mark of the drug; 
(b) The expiration date of the drug; 
(c) The recommended storage conditions of the drug; 
(d) The donor identification number 
 
After collection, processing, and completion of donor regulatory analyses, the product will be 
shipped to the hospital blood bank for storage. A segregated storage area will be set up and used 
to keep the CCP apart from the other plasma products. A product list will be kept up to date in 
order to know at all times the number of units available and their corresponding blood volumes 
and ABO types. 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
36 
 Anti-SARS-CoV-2 seropositivity  
5.6.
There is currently no clinically validated method to characterize the therapeutic potency of COVID-
19 convalescent plasma. Importantly, non-convalescent plasma selected from the general 
population based on titers of neutralizing antibodies did not show efficacy in the treatment of 
influenza in 3 large RCTs questioning reliance of such assay to predict efficacy45–47. Because the 
validity of such assays to determine the therapeutic value of CCP constitutes an important clinical 
question, the neutralizing activity of plasma samples will be documented for all samples and 
correlated with treatment effect as an exploratory objective. These assays can be performed 
before or after the plasma has been released.  
 
However, as a minimal requirement, anti-SARS-CoV-2 seropositivity must be demonstrated on 
donor sample prior to release of product. This can be done by ELISA or with a neutralizing assay. In 
the U.S sites, seropositivity may be assessed after transfusion of the product for a minority of 
donors. The majority of donors will be referred by the treating center to the donor center and pre-
screened for seropositivity prior to donation. However, if CCP units from the referred donors are 
unavailable, a general pool of CCP plasma can be used with seropositivity assessed from a tail 
segment following transfusion. 
 
 ELISA or Chemoluminescence 
5.6.1.
The ELISA or Chemoluminescence will specifically test for antibodies directed against the receptor 
binding domain (RBD) of SARS-CoV-2 glycoprotein S, which have been reported to correlated with 
plasma neutralizing activity (R2=0.96) 48.  
 
The American Association of Blood Banks (AABB) provides no guidance with regards to a specific 
titer cut-off value to qualify convalescent plasma as the optimal titer is currently unknown. The 
cut-off for seropositivity will be set as the mean value + 3 SD of the ELISA signal obtained with 
SARS-CoV-2 negative plasma (pool of plasma samples collected before 2020) at a 1:100 plasma 
dilution. 
 
 Functional assays 
5.6.2.
Functional neutralization assays can also be used as a criteria to confirm seropositivity. The most 
direct method involves adding the diluted plasma to a specific number of infectious particles (in 
this case SARS-CoV-2 virus), plating the virus, and measuring the number of plaques that can still 
be formed. This provides insights into the levels of neutralizing antibodies and for treating Covid-
19. If used to qualify donation, a dilution of 1/160 will be used as threshold neutralizing titer will 
be used to confirm donor eligibility.  
 
The antibody-dependent cell cytotoxicity assay, which measure Fc function of antibodies will also 
be performed on all plasma samples as per the study’s exploratory objective but will not be used 
as a criteria to qualify donations. 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
37 
 Administration  
5.7.
The investigational product will be administered by a bedside nurse or other clinical team member 
that is qualified and licensed to administer blood products. Administration date and time, will be 
entered into the case report form (CRF). The one (500 mL) or two (250 mL) plasma units collected 
from one or two donors will be considered one treatment dose. 
a. The plasma will be administered at an infusion rate of no more than 150 mL/h and a standard 
test dose of 50 mL/hour for the 15 minutes or as per local procedures is mandatory. 
b. If an AE develops during infusion, the infusion will be stopped and can be restarted as per 
investigator’s decision in consultation with the bedside physician.  
i. Most reactions to plasma are relatively minor (urticaria or volume overload) and the 
infusion can generally be continued. Infusion can generally be continued in cases of itching 
or urticarial reactions after pausing the transfusion, administering antihistamines, and 
observing the patient for worsening.   
c. Severe allergic reactions such as, bronchospasm and hypotension, and will require 
discontinuation of the infusion. 
d. Transfusion of each unit must be completed within 4 hours of removal from storage. The 
complete study product (either 1 x 500 mL or 2 x 250 mL) must be infused within 24 hours of 
randomization. 
e. No medication or solution may be added to or infused through the same tubing 
simultaneously, unless the solution has been approved by Health Canada for this use (i.e. 
normal saline).  
f. Participants must be under direct or remote observation during the first 15 minutes. Vital 
signs should be assessed at 15 minutes, midway through the infusion and at the end of the 
infusion. 
 
The maximum tolerated dose of AFP has not been determined. The most likely adverse effect from 
the transfusion would be hypervolemia which may be treated with diuretics in symptomatic 
patients by the bedside physician. Any over-dosage needs to be reported as per section 9.10.2. 
 
 Dose of CCP 
5.8.
The dose of CCP will be approximately 500 mL. This will be administered as be either 1 unit of 500 
mL or 2 units of 250 mL of apheresis CCP.   
 
 Return and/or Destruction of Investigational Product 
5.9.
After the study treatment period has ended or as appropriate over the course of the study, 
disposition of unused and used plasma will occur following site procedures in the study protocol. In 
the context of the COVID-19 pandemic, this may include disposal of the used plasma in the 
biohazard disposal in the patient room. The final disposition of the product will be confirmed in the 
Laboratory Information System used by the hospital Blood Bank and provided to the investigator 
team to be kept in the investigational product log. These logs will be verified periodically by study 
monitors. Any site found to use a study product on a non-CONCOR-1 trial patient will be 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
38 
immediately suspended to trial enrollment and the local REB/IRB and regulatory authorities will be 
notified. 
 
At the completion of the study, there will be a final reconciliation of investigational product 
shipped, used, and remaining. This reconciliation will be documented. Any discrepancies noted 
will be investigated, resolved, and documented prior to return or destruction of unused 
investigational product. Documentation of investigational product destroyed on site will be 
retained in the study files. 
 
 
Blinding and Breaking the Blind 
5.10.
This is an open-label trial. 
 
 
Investigational Product Accountability 
5.11.
The site PI is responsible for study product distribution and disposition and has ultimate 
responsibility for study product accountability. The site PI may delegate to the participating site’s 
blood bank responsibility for study product accountability.  
 
The participating site’s blood bank will be responsible for maintaining complete records and 
documentation of study product receipt, accountability, dispensation, storage conditions, and 
final disposition of the study product(s). 
 
All study product(s), whether administered or not, must be documented on the appropriate study 
product accountability record or dispensing log. The sponsor’s monitoring staff will verify the 
participating site’s study product accountability records and dispensing logs per the site 
monitoring plan. 
 
 
Compliance 
5.12.
CCP will be transfused in the clinical area by the patient’s nurse or physician, with oversight from 
the study team (site PI and/or site RA) who will not enter the room, thereby ensuring compliance 
with the investigational product and good practices in the context of the COVID-19 pandemic. 
 
 
Prior and Concomitant Medication 
5.13.
A concomitant medication is any treatment received by the subject concomitantly to any 
investigational medicinal products (IMPs) or during study participation. 
 
Concomitant medications in a hospitalized population change daily and are difficult to collect 
and attribute to success and failure of therapy and impact on safety. Therefore, only selected 
concomitant medications will be recorded in this trial. The list of medications will be assessed 
only from 7 days prior to enrolment to Day 30 or discharge, whichever comes first, and will be 
detailed in the study operations manual. 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
39 
 STUDY OUTCOMES 
6.
 Primary Outcome:  
6.1.
The primary outcome is a composite of intubation or death at Day 30. 
 
 Secondary Outcomes: 
6.2.
 Time to intubation or death  
 Ventilator-free days  
 In-hospital death by Day 90  
 Time to in-hospital death  
 Death by  Day 30  
 Length of stay in ICU  
 Length of stay in hospital  
 Need for ECMO 
 Need for renal replacement therapy 
 Myocarditis 
 Patient-reported outcome at Day 30 
 Incremental cost per quality-adjusted life year (QALY) 
 CPP transfusion-associated AEs 
 Grade 3 and 4 SAEs  
 Cumulative incidence of Grade 3 and 4 SAEs (CTCAE) 
 
 DURATION OF FOLLOW-UP 
7.
Subjects will be followed daily until hospital discharge or death. Patients discharged from hospital 
before Day 30 will be contacted by telephone on Day 30 ± 3 days to ascertain any AEs, vital status 
(dead/ alive), hospital readmission and need for mechanical ventilation after discharge. Patients 
with a prolonged hospital admission will be censored for the outcome of in-hospital death at Day 
90. 
 
For patients who are pregnant or who become aware that they are pregnant between the period 
of randomization and Day 30, we will record their expected date of delivery and we will contact 
the patient after delivery to obtain information regarding any maternal or fetal adverse outcomes. 
 
 
 
 
 
 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
40 
 DATA COLLECTION AND SCHEDULE OF EVENTS 
8.
The local study coordinator will collect all study data and record the data in the CRF (electronic 
and/or paper) as per local study procedures and requirements for each site. 
 
 Data to be collected from the blood supplier 
8.1.
De-identified data on the plasma donor will be obtained from the blood suppliers. For Canadian 
and Brazilian sites, this data will include unit information (such as ABO group, volume, antibody 
titre) and donor information (such as age, sex, symptom onset, severity, treatment, date of 
resolution) and will be sent via secure file transfer in accordance with institutional protocols. For 
US sites and the Israeli site, the data will include ABO group, volume, antibody titre 
(retrospectively) and donor information (such as age, sex, symptom onset, date of resolution) and 
will be sent via secure file transfer in accordance with institutional protocols. 
 
 Subject Screening 
8.2.
At each participating site, there will be a process developed to immediately identify patients 
admitted to hospital with COVID-19. The local RA will then screen the patient for study eligibility, 
provide study details to the patient, and seek informed consent. Information from all patients 
approached for the study will be documented and logged using the screening study number 
including reasons for any exclusion. Once informed consent is obtained, a screening ABO blood 
group will be performed if one was not already performed during the patient’s current hospital 
admission.  
Once the ABO blood group testing has been performed, the remaining sample (discard) will be 
retained for future testing. Alternatively, an extra tube can be added to the routine blood draw for 
research. 
 
 Collection of daily hospital data  
8.3.
Baseline data will be collected on Day 1 (see Section 8.5). 
 
During the index hospital admission, daily data will be collected until discharge or Day 30 from 
randomization, whichever comes first. For enrolled patients who are still in hospital beyond Day 
30, the date of discharge or death will be recorded up until Day 90 at which point data collection 
will be censored. This information will be obtained by reviewing the medical chart, by telephone 
follow-up or, if feasible through, provincial/state or national databases. 
 
If the patient has routine blood drawn for laboratory testing pre-randomization and between 24 
hours and 5 days (sample closest to 48 hours will be selected in preference) post-randomization, 
the discard plasma/serum from that sample will be retrieved, aliquoted and frozen for future 
testing. Alternatively, an extra tube can be added to the routine blood draw for research. 
 
A Schedule of Assessment Events is available below for reference. 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
41 
 
 
Schedule of Assessment Events 
 
 
 
 
Follow up 
Visit 
Screening 
Baseline 
(D1) 
D2 – D30(1) 
(or until 
discharge) 
D30(2)  
(if patients 
discharged) 
D90 
Time Window (days)  
 
  
  
+/- 3  
+/- 7 days 
Informed Consent/Assent  
X 
 
 
 
 
Verify Eligibility Criteria  
X 
 
 
 
 
Randomization  
  
X 
  
  
 
CCP Administration (3)  
  
X 
  
  
 
Demographics  
 
X 
 
 
 
Co-morbidities  
 
X 
 
 
 
COVID-19 History(4) 
 
X 
 
 
 
Height and Weight 
 
X 
 
 
 
Vital Signs 
 
X 
 
 
 
SpO2 
 
X 
X 
 
 
FiO2   
 
X 
X 
 
 
COVID treatments 
 
X 
X 
X 
 
Hospitalization Daily Assessment (5) 
  
X 
X 
 
 
Results of blood tests (done as per 
clinical need) 
  
X 
X(6) 
 
 
EQ-5D-5L(7) 
 
X 
 
X 
 
Vital Status (dead/ alive) 
  
 
X 
X 
X 
Adverse Event Review 
  
X 
X 
X 
 
Discharge status (8) 
 
 
 
X 
 
Mechanical Ventilation since discharge 
  
  
 
X 
 
Viral load, cytokines and anti-CoV-2 
titers(9) 
 
X 
X 
 
 
 
(1) Only collected if still hospitalized 
(2) Phone call if subject is already discharged from the hospital  
(3) Only for subject randomized to the convalescent plasma treatment 
(4) Includes date of first symptoms; description of symptoms, and date of diagnostic test 
(5) Mechanical ventilation, ECMO, renal replacement therapy or myocarditis  
(6) Daily from Day 1-7, then Day 14 +/- 3 days 
(7) EQ-5D-5L to be collected on Day 1 after consent and prior to CCP administration and on Day 30 regardless of hospitalization status 
(8) Discharge or hospital status (admitted, home, local hospital, longterm care facility) 
(9) To be performed using frozen leftover sample or extra tube collected once at baseline and once during follow-up 
between 24h and 5 days post-randomization for both arms 
 
 
 
 
 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
42 
 Baseline/Enrollment (Study Day 1) 
8.4.
Procedures/Assessments/Evaluations in this section will be completed after consent has been 
obtained, eligibility has been confirmed and the subject has been randomized. These do not need 
to be performed in the order listed below, but the administration of CCP must be the last 
procedure to be completed. 
1- Demographics 
2- Co-morbidities 
3-  Smoking status and pack-years for smokers 
4- COVID-19 history (symptom onset, date of test, results of test) 
5- Admission date 
6- Oxygen saturation and PaO2 (where available) 
7- FiO2 and oxygen requirement (nasal prongs, oxygen masks, high-flow nasal cannula,  
noninvasive positive pressure ventilation) 
8- Vital signs (temperature, pulse, respiratory rate, height, weight, and blood pressure) 
9- Lab values 
10- Patient-reported outcome instrument  EQl-5D-5L 49  
11- AEs since screening (if screening was not completed on the same day) 
12- Concomitant medication review (if screening was not completed on the same day) 
13-  COVID-19 concomitant treatments including co-enrolment in another clinical trial 
14- Administration of investigational product (according to study arm) 
 
 Collection of daily hospital data (Study Day 2 until discharge, death or Day 30 post 
8.5.
randomization). 
The following data and procedures will be collected daily.   
1- Oxygen saturation and FiO2 
2- Mechanical ventilation requirement (via endotracheal tube or tracheostomy tube) 
3- Admission to ICU 
4- ECMO requirement 
5- Renal replacement therapy requirement 
6- Myocarditis 
7- COVID-19 concomitant treatments 
8- Blood product and blood transfusion information 
9- AEs  
10- Concomitant medication review 
11- Chest x-ray and CT chest results 
12- Discharge status (home, transfer to another facility, palliative discharge) - collected from the 
hospital chart 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
43 
 
 Laboratory Test Results 
8.6.
The following laboratory testing results will be recorded only if ordered by the bedside team at 
baseline (most recent results from day of randomization or previous 2 days), daily until Day 7, 
and at Day 14 (+/- 3 days). 
   
1. CBC 
2. INR, PT, aPTT, Fibrinogen, D-dimer 
3. ALT, ALP, Bilirubin (total) 
4. Albumin 
5. Creatinine 
6. LD 
7. CK, C-Reactive Protein, Total Protein 
8. Blood gas results (PaO2, PaCO2) 
9. Ferritin 
10. Total CO2 
11. Troponin I HS 
12. Lactate 
 
 Discharge  
8.7.
1. Hospital / Discharge status (home/local hospital/longterm care facility) 
2. Oxygen requirement 
3. Need for mechanical ventilation 
4. AEs 
 
 Day 30 
8.8.
1. Vital status (dead or alive) 
2. Requirement for mechanical ventilation since discharge 
3. Oxygen requirement 
4. Hospital status (home/local hospital/longterm care facility) 
5. Readmission to hospital (if discharged home/longterm care facility) 
6. EQ-5D-5L 
7. AEs 
 
 Day 90 follow-up 
8.9.
Occurrence and date of hospital death or discharge (for participants still hospitalized at Day 30 
only).  
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
44 
 
Protocol Deviations 
8.10.
A protocol deviation is any noncompliance with the clinical trial protocol, any process that is noted 
in the protocol and refers to details in the protocol-specific operations manual or Good Clinical 
Practice (GCP) requirements or any critical study procedures with specific instructions in ancillary 
documents referenced in the protocol such as a protocol-specific operations manual. 
 
It is the responsibility of the investigator to ensure that only investigative procedures, as outlined 
in this protocol are performed on study participants; the occurrence of deviations from the 
protocol or SOPs are limited; and compliance with the regulations is maintained. Planned 
deviations from the protocol must not be implemented without prior agreement from the sponsor 
and approval from the local REB/ethics committee, as required, unless to eliminate an immediate 
hazard to a participant. 
 
Planned or unplanned deviations may occur on the part of the participant, the investigator, or 
study research team. In resolution to a deviation, corrective/preventative actions are to be 
developed and implemented in a timely manner. Protocol deviations will be documented and 
reported as required and assessed where necessary during analysis. All individual protocol 
deviations will be addressed in subject study records. 
 
It is the responsibility of the site PI and personnel to use continuous vigilance to identify and 
report deviations within five working days of identification of the protocol deviation, or within five 
working days of the scheduled protocol-required activity. All deviations must be promptly 
reported per the protocol deviation reporting procedures. Protocol deviations must be sent to the 
local REB per their guidelines. The site PI and personnel are responsible for knowing and adhering 
to their REB requirements. A completed copy of the Protocol Deviation Form must be maintained 
in the Essential Documents, as well as in the subject’s chart if the deviation is subject specific. 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
45 
 SAFETY VARIABLES 
9.
 Adverse Event 
9.1.
An AE is any untoward medical occurrence that occurs in a patient or clinical investigation subject 
administered a pharmaceutical product, and which does not necessarily have a causal relationship 
with the treatment assignment. An AE can therefore be any unfavorable and unintended sign 
(including abnormal laboratory finding), symptom, or disease temporally associated with the use 
of an investigational product, whether or not considered related to the product. 
 
Because this is a trial focusing on a critically ill population where serious adverse events and death 
are expected to occur frequently, AE reporting will follow recommendations set out for trials in 
this population by Cook and colleagues50. During this trial, investigators will need to document all 
AEs that are definitely or probably related to the intervention (defined in 9.4.1), and events that 
are grade 3 or higher for all other AEs.   
 
These will be documented on the paper CRF and in the electronic CRF (e-CRF) with the 
maintenance of all source documentation in the patient research file. Concomitant illnesses, which 
existed before entry into the study, will not be considered AEs unless they unexpectedly worsen 
during the treatment period. AEs must be documented regardless of the source of identification 
(for example physical examination, laboratory assessment, reported by subject). 
 
 Serious Adverse Event 
9.2.
A SAE is generally defined as any untoward medical occurrence that at any dose: 
1. Results in death; 
2. Is life-threatening; this means that the subject is at risk of death at the time of the event; it 
does not mean that the event hypothetically might have caused death if it was more severe; 
3. Requires hospitalization (overnight or longer) or prolongation of existing hospitalization or 
invasive procedure; 
4. Results in persistent or significant disability or incapacity; 
5. Results in congenital anomaly or birth defect; 
6. Is not be immediately life-threatening or result in death or hospitalization but may jeopardize 
the subject or require intervention to prevent one of the above outcomes.  
 
Events associated with hospitalization for the following will not be considered as an SAE:  
1. Evaluation or treatment of a pre-existing and non-exacerbating condition as long as the 
condition is associated with the hospitalization (e.g. hospitalization for investigation of a 
benign disorder);  
 
2. Existed prior to the subject’s entry into the study and has been recorded in the subject’s 
disease/medical history as documented in the e-CRF; 

 
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46 
3. Has not worsened in severity or frequency during the subject’s exposure to investigational 
product; 
4. Has not required a change in treatment management during the subject’s exposure to the 
investigational product; 
5. Elective or pre-planned treatment of a pre-existing and non-exacerbating condition. 
 
In the specific context of a clinical trial focussing on a critically ill population, the definition of SAE 
also excludes:  
a. AEs that are part of the natural history of the primary disease process or expected 
complications of critical illness. 
b. AEs that are already captured as study outcomes. 
Medical and scientific judgment should be exercised in deciding whether an AEs is serious and 
whether expedited reporting is appropriate. Caution must also be exercised by the investigator 
when attributing death or prolonged hospitalization to a specific AE. All-cause mortality and 
hospitalization stay will be captured as study outcomes. 
 
 Severity of Adverse Events 
9.3.
The severity of each AE must be assessed by the Investigator and graded based on CTCAE v4.0. A 
clinical AE NOT identified elsewhere in the grading table will be graded using one of the following 
categories: 
1. Mild: Mild symptoms causing no or minimal interference with usual social & functional 
activities with intervention not indicated 
2. Moderate: Moderate symptoms causing greater than minimal interference with usual social & 
functional activities with intervention indicated 
3. Severe: Severe symptoms causing inability to perform usual social and functional activities 
with intervention or hospitalization indicated 
4. Life-threatening: Potentially life-threatening symptoms causing inability to perform basic self-
care functions with intervention indicated to prevent permanent impairment, persistent 
disability, or death. 
5. Death: The AE resulted in the subject’s death. 
 
 Causality of Adverse Event 
9.4.
 Relation to investigational product 
9.4.1.
The Investigator will assess the causality/relationship between the investigational product and the 
AE and record that assessment in the source documents and in the e-CRF. The most likely cause of 
an AE/SAE (for example disease under treatment, concomitant disease, concomitant medication, 
other) will be indicated in the e-CRF.  

 
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47 
In the absence of a definite causal relationship, any adverse event that is considered to have a 
reasonable causal relationship with the investigational product should be classified as “probably 
related.” 
 
The causal relationship of the AE to investigational product will be described in terms of: 
 
1. Related. The AE: 
1. Follows a clear temporal sequence from administration of the investigational product. 
2. Has no other possible explanations, such as the subject’s clinical state, environmental or 
toxic factors or other therapies administrated to the subject. 
3. Disappears or decreases on cessation or reduction in dose of the investigational product. 
4. Follows a clear pattern of response to the investigational product. 
5. Reappears or worsens upon re-challenge. 
 
2. Probable. The AE: 
1. Follows a reasonable temporal sequence from administration of the investigational 
product. 
2. Could not be reasonably explained by the subject’s clinical state, environmental or toxic 
factors or other therapies administrated to the subject. 
3. Disappears or decreases on cessation or dose reduction of the investigational product. 
4. Follows a known pattern of response to the investigational product. 
5. Reappears or worsens upon re-challenge. 
 
3. Possible. The AE: 
1. Follows a reasonable temporal sequence from administration of the investigational 
product. 
2. Could be reasonably explained by the subject’s clinical state, environmental or toxic factors 
or other therapies administrated to the subject. 
3. Follows a known pattern of response to the investigational product. 
 
4. Unlikely. The AE: 
1. Does not follow a reasonable temporal sequence from administration of the investigational 
product. 
2. Could be reasonably explained by the subject’s clinical state, environmental or toxic factors 
or other therapies administrated to the subject. 
3. Does not follow a known pattern of response to the investigational product. 
4. Does not reappear or worsen upon re-challenge. 
 
 

 
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48 
5. Not related.  
1. The AE does not meet the above criteria. 
2. There is sufficient information that the etiology of the AE is not related to the 
investigational product. 
 
 Recording Adverse Events occurring after the end of the study 
9.5.
Adverse events occurring after the end of the study should be reported to the Sponsor by the 
Investigator if the Investigator considers that there is a causal relationship with the investigational 
product. 
 
 Adverse Event Reporting 
9.6.
At each clinical evaluation, the Investigator will determine whether any AEs have occurred. AEs 
will be recorded in the AE page of the e-CRF as well as in the source documents.  
 
Coding of AEs will be performed using MedDRA (https://www.meddra.org/). All AE reports in the 
e-CRF should contain the following information of the event: date of onset, severity, relationship 
to investigational product, outcome at Day 30, and whether the event is classified as serious or 
not.  
 
 Serious Adverse Event Reporting 
9.6.1.
SAEs that are unexpected and either definitively or probably related to the investigational 
products (Suspected Unexpected Serious Adverse Reactions – SUSARs) must be reported to the 
sponsor.  SAEs that are expected and either definitively or probably related to the investigational 
product and non-CCP related SAEs that meet reporting criteria (unexpected in the context of 
COVID-19, critical illness, or a baseline medical condition; or not already reported as a study 
outcome) must also be reported to the sponsor. 
 
In the event of a SAE, the Investigator must: 
1. Enter all relevant information in the AE page of the eCRF. 
2. Inform the Sponsor of the SAE via email or telephone within 96 hours of becoming aware of 
the SAE (or within 24 hours if SAE is unexpected and related to investigational product, see 
section 9.8). 
3. Complete the SAE reporting form in the EDC.  
 
The minimum information required for an initial report is: 
1- Name of person sending the report (that is name and address of Investigator); 
2- Confirmation that the patient was in the active treatment arm; 
3- Subject identification (screening number, NOT the subject’s name); 
4- Protocol number; 
5- Description of the SAE including a comprehensive verbatim term; 

 
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6- Event onset date; 
7- Causality assessment, if possible. 
 
However, as far as possible, all points in the SAE pages in the e-CRF and on the SAE Report Form 
should be covered in the initial report.  
 
SAE update reports should be submitted to the Sponsor when additional relevant information 
becomes available. 
 
Suspected unexpected serious adverse reactions (SUSARS) will be submitted by the Sponsor or its 
representative to the Regulatory Authorities according to local guidelines. 
 
 Sponsor Reporting of SUSARs: Notifying Health Canada 
9.6.2.
The regulatory sponsor (or its delegate) is responsible for reporting SUSARs to regulatory 
authorities in accordance with local expedited reporting requirements and timelines. In addition, 
the Sponsor will complete the Adverse Drug Reaction Expedited Reporting Summary Form and 
submit this form to the appropriate Health Canada directorate. 
 
Any unexpected fatal or life-threatening suspected adverse reaction will be reported to the 
regulatory authority as soon as possible, but in no case later than 7 calendar days after the 
sponsor’s initial receipt of the information. If the event is not fatal or life-threatening, the safety 
report will be submitted within 15 calendar days after the sponsor determines that the 
information qualifies for reporting. Relevant follow up information to safety report will be 
submitted as soon as the information is available. Upon request from regulatory authority, the 
sponsor will submit any additional data or information that the agency deems necessary, as soon 
as possible, but in no case later than 15 calendar days after receiving the request. 
 Reporting of Serious Adverse Events to the FDA 
9.6.3.
The U.S. site regulatory sponsor/sponsor representative is responsible for notifying the FDA of any 
suspected adverse reaction to study treatment that is both serious and unexpected to the FDA. 
The event will be filed on the FDA Form 3500A and submitted as soon as possible but no later than 
7 calendar days after the initial receipt of the information to CBER. 
 
All transfusion-related fatalities must be reported as soon as possible to Food and Drug 
Administration (FDA), Center for Biologics Evaluation and Research (CBER), Office of Compliance 
and Biologics Quality (OCBQ) after confirming a complication of blood collection or transfusion to 
be fatal. The collecting facility is to report donor fatalities, and the compatibility testing facility is 
to report recipient fatalities. The regulation also requires the reporting facility to submit a report 
of the investigation within 7 days after the fatality. 
 
 
 

 
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50 
 Reporting of Serious Adverse Events to Agência Nacional de Vigilância Sanitária 
9.6.4.
(ANVISA-Brazil) 
 
The regulatory sponsor/sponsor representative (or its delegate) is responsible for reporting 
Adverse Events to national regulatory authorities (ANVISA)  in accordance with local expedited 
reporting requirements and timelines. Relevant follow up information to safety report will be 
submitted as soon as the information is available. Upon request from regulatory authority, the 
sponsor will submit any additional data or information that the agency deems necessary, as soon 
as possible, but in no case later than 15 calendar days after receiving the request. 
 
The sponsor will also notify the local IRB and CONEP, within a maximum period of 24 hours, of any 
serious adverse event, suspected of having been caused by the proposed treatment (including 
death).  
 
 
 Reporting of Serious Adverse Events to the Meir Medical Centre Ethics Committee 
9.6.5.
and Israeli Ministry of Health 
 
The Israeli site regulatory sponsor/sponsor representative is responsible for notifying the Meir 
Medical Center Ethics Committee and to the Israeli Ministry of Health when considered necessary 
by the former body, of any suspected adverse reaction to study treatment that is both serious and 
unexpected. The event will be reported as soon as possible but no later than 7 calendar days after 
the initial receipt of the information. 
 
 Sponsor Reporting of SUSARs: Notifying Sites 
9.6.6.
The regulatory sponsor is responsible for distributing expedited reports of SUSARs to each 
investigator for submission to local Ethics Committees within 15 days of sponsor awareness.  
U.S. site regulatory sponsor/sponsor representative is responsible for submitting all SUSARs that 
meet criteria to the FDA.  
Brazilian site regulatory sponsor/sponsor representative is responsible for submitting all SUSARs 
that meet criteria to ANVISA.   
 
 Type and Duration of Follow-up for Adverse Events 
9.7.
AE collection will begin at randomization and end at Day 30.Unresolved events at Day 30 will be 
marked as “ongoing at Day 30.” 
 
Adverse events will be monitored until Day 30. For participants still hospitalized at Day 30, hospital 
mortality will be followed up on Day 90. 
 
 Reporting and Entry Timelines 
9.8.
Study investigators will report SAEs to the sponsor within the following timelines: 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
51 
 
All serious and unexpected events deemed to be related to investigational product 
(suspected unexpected serious adverse reaction (SUSAR)) will be recorded and reported to 
the sponsor within 24 hours of site awareness. 
 
All other SAEs  will be reported to the sponsor within 96 hours of site awareness. 
 
Adverse event information will be entered into the CRF in a timely manner and no later than 7 
days from the time the investigator becomes aware of the event. 
 
Serious adverse event information will be entered into the CRF in a timely manner/within 96 hours 
from the time the investigator becomes aware of the event (or 24h for SUSARs). 
 
 Reporting of Events Other than Serious Adverse Event 
9.9.
Even if none of the criteria for a SAE are fulfilled, any of the following events must be reported by 
the Investigator to the Sponsor within 24 hours from the time the Investigator is notified.  
 Transfusion associated acute lung injury (TRALI) 
 Transfusion associated circulatory overload (TACO) 
 
 
Adverse Events to Convalescent Plasma Transfusion  
9.10.
AEs to CCP will be categorized using the ISBT definitions for diagnosis, severity and imputability. 
AEs to any other blood products that the patient receives during the hospitalization will reported 
as AEs as well as declared following normal procedures in place locally. 
 
 Pregnancy  
9.10.1.
The Sponsor has a responsibility to monitor the outcome of pregnancies where there has been 
maternal exposure to the investigational product. Pregnancy alone is not regarded as a 
contraindication to participation in the trial or as an AE unless there is a suspicion that the 
investigational product may have interfered with the effectiveness of a contraceptive medication. 
Elective abortions without complications should not be handled as AEs, unless they were 
therapeutic abortions (see below). Hospitalization for normal delivery of a healthy newborn will 
not be considered a SAE.   
 
All pregnancies occurring in the CCP group must be reported by the Investigator to Sponsor on a 
separate  CRF within 24 hours after becoming aware of the pregnancy. The Investigator must 
follow up and document the course and the outcome of all pregnancies even if the subject was 
discontinued from the study or if the study has finished. All outcomes of pregnancy must be 
reported by the Investigator to the Sponsor on a specific pregnancy CRF within 96 hours after 
she/he has gained knowledge of the normal delivery or elective abortion. 
 
Any SAE related to investigational product that occurs during pregnancy (including SAEs occurring 
after last administration of investigational product) must be recorded in the SAE pages in the CRF 
(for example serious maternal complications, spontaneous or therapeutic abortion, ectopic 

 
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52 
pregnancy, stillbirth, neonatal death, congenital anomaly, or birth defect) and reported within 96 
hours in accordance with the procedure for reporting SAEs. 
 
 Treatment of Overdose of investigational product 
9.10.2.
Overdose is unlikely since only the required amount of CCP will be issued to a patient. In the 
unlikely event of inadvertent overdose due to human error, with or without associated AEs, the 
event will be reported to the Sponsor as per procedures outlined in the operations manual. 
Overdose will be reported to the sponsor within 24 hours of learning of the overdose. Any AEs 
associated with the overdose should be reported in the relevant AE/SAE sections in the CRF. 
 
 INDEPENDENT COMMITTEES 
10.
 
 
Independent Data Safety Monitoring Committee 
10.1.
Safety oversight will be conducted by an independent data safety monitoring committee (IDSMC) 
that is an independent group of experts that monitors subject safety. The IDSMC members will be 
separate and independent of study personnel participating in this trial and should not have 
scientific, financial or other conflict of interest related to this trial.  
 
The IDSMC will consist of members with appropriate expertise to contribute to the interpretation 
of the data from this trial. The IDSMC should be as broadly informed as possible regarding 
emerging evidence from related studies as well as from the conduct of the Master Protocol from 
which this was adapted. The IDSMC will operate under the guidelines of a charter that will be 
written at the organizational meeting of the IDSMBC. The IDSMC will review SAEs on a regular 
basis and ad hoc during the trial according to the IDSMC charter. 
 
The study will not stop enrolment awaiting these IDSMC reviews, though the IDSMC may 
recommend temporary or permanent cessation of enrolment based on their safety reviews. 
 
Additional data may be requested by the IDSMC, and interim statistical reports may be generated 
as deemed necessary and appropriate. The IDSMC may receive data in aggregate and presented 
by treatment arm. The IDSMC may also be provided with expected and observed rates of the 
expected AEs in an unblinded fashion and may request the treatment assignment be unblinded for 
an individual subject if required for safety assessment. The IDSMC will review grouped and 
unblinded data in closed sessions only. As an outcome of each review/meeting, the IDSMC will 
make a recommendation as to the advisability of proceeding with study interventions (as 
applicable), and to continue, modify, or terminate this trial. Criteria for stopping the trial due to 
harm are left to the judgement and discretion of the IDSMC as outlined in the charter of the 
IDSMC. 
 
 
 
 
 

 
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53 
 
Community Advisory Committee 
10.2.
A Community Advisory Committee (CAC) will be established to bring a diversity of perspectives 
based on relevant lived experiences and socio-demographic characteristics (e.g. age, sex/gender, 
education, ethnicity) to the CONCOR-1 Trial. The CAC will consist of 7-9 selected individuals, in 
addition to a CONCOR-1 Steering Committee Member, who will sit on the CAC, and act as a liaison 
to the overall trial, helping the CAC members to facilitate their discussions. Members from the 
patient community will be invited to apply to join the CAC. Additionally, the CAC will have 
representatives that are donors of plasma, recipients of plasma/COVID-19 patients and family 
members or caregivers of recipients/donors. Applicants to the CAC will be selected based on their 
Various Geographical locations, their status as Marginalized Individuals, Indigenous Individuals, 
Disabled Peoples/ Peoples with existing illnesses, Participants in the trial, and Severity of sickness 
with COVID-19. Broad recruitment of participating sites that include both academic and 
community hospitals in Canada will maximize access to the trial for patients. Individuals will be 
recruited to be a part of the CAC through various community engagement networks, such as the 
SPOR Network and the McMaster University Office of Community Engagement.  
 
Advisors from marginalized populations affected by the pandemic will help advocate for access to 
the trial and to study results for people who are often excluded from research such as residents of 
long term care facilities, African American and Indigenous people.51,52 Goals of this committee are 
1) to maximize the relevance of the research for the community; 2) to advise on equitable 
distribution of CCP; 3) to provide input on equitable recruitment of trial participants; 4) to provide 
feedback on analyses including awareness of the effects of social determinants, 5) to enhance 
effective dissemination of study results; and, 6) to create a space of inclusivity for participants to 
engage as a community and share their experiences with COVID-19.52,53  Creation of the CAC will 
build capacity for future citizen engagement initiatives within the Canadian Transfusion Research 
Network. 
 
 
 
 
 

 
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54 
 SITE MONITORING, AUDITING AND INSPECTING 
11.
 
Informed Consent  
11.1.
Consent will be obtained for donors through Canadian Blood Services and Héma-Québec (separate 
REB application at both Canadian Blood Services and Héma-Québec). In the U.S., consent will be 
obtained by the New York Blood Center through a separate IRB application, as well as by Hemorio 
for the Brazilian sites and by Magen David Adom National Blood Services for the Israeli site.  
 
The Investigator is responsible for ensuring informed consent is obtained from each hospitalized 
participant.  
 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s), should adhere to GCP and to the ethical principles that have 
their origin in the Declaration of Helsinki. Prior to the beginning of the trial, the Investigator will 
have their applicable REB/Institutional Review Board (IRB)/independent ethics committee’s (IEC) 
written approval/favourable opinion of the written informed consent form and any other 
information to be provided to subjects. 
 
Documentation of informed consent must be dated and retained by the Investigator as part of the 
study records. The Investigator will not undertake any investigation specifically required only for 
the clinical study until valid consent has been obtained. Sites must follow local informed consent 
policies and guidelines.  
 
Subjects will be informed of the nature of the study, its aim, its possible risks and restrictions, its 
duration, and any compensation that they may receive. The trial and participant responsibilities 
will be explained during the informed consent discussion prior to study enrollment, and each 
subject must be informed that their participation in the study is voluntary and that they may 
withdraw from the study at any time. The subject or their legally authorized representative (LAR) 
must read or fully understand the study/ICF and have an opportunity to ask questions before they 
provide consent to participate. Where applicable, the participant may be asked to sign a paper 
copy of the consent, prior to discharge, where it is safe to do so, for both the patient and health 
care team. A copy of the signed informed consent or documentation of remote consent must be 
made a part of the subject’s medical file and a copy provided to the patient or their legally 
authorized representative.  
 
If a protocol amendment is required, the ICF may need to be revised to reflect the changes to the 
protocol or safety profile. If the consent form is revised, it must be reviewed and approved by the 
appropriate REB/IRB/IEC, and may need to be re-signed by the subjects or LAR previously enrolled 
in the study as well as those currently enrolled in the study before Day 30. Sites should follow local 
policies and guidelines.  
 
The Investigator should inform the subject’s primary physician about participation in the clinical 
study where applicable. 

 
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55 
 
Data Quality Assurance  
11.2.
The Sponsor or Sponsor’s designee will conduct a site visit or a site phone contact to verify the 
qualification of each Investigator, review the site facilities, and inform the Investigator of her/his 
responsibilities and the required procedures for ensuring adequate site selection and correct 
documentation. On-site visits may be restricted due to site local visitor and research personnel 
restrictions. Where necessary, virtual site visits will continue to ensure compliance with the study 
protocol and procedures. 
 
 Database Management and Quality Control  
11.2.1.
All data generated by the site personnel will be captured electronically at each study centre using 
e-CRFs. Data from external sources (such as laboratory data) will be inputted manually. 
 
Once clinical data are entered and validated in the e-CRF, they are transmitted and recorded by 
the central server in the central database. Computerized edit-checks will be developed in addition 
to manual review to detect any discrepancies and to ensure consistency of the data. 
 
The appropriate staff at the study site will answer queries sent to the site. The reason for changes, 
the name of the person who performed the changes, together with the time and date will be 
automatically recorded by the Electronic Data Capture (EDC). An electronic audit trail system will 
be used to track all data changes in the database subsequent to the first data entry. 
 
If additional corrections are needed, the responsible monitor, data manager or the Sponsor will 
raise a query in the EDC application. Appropriate feedback to the study staff or other corrective 
measures will be undertaken if any missing data, inconsistent data, outlier data and potential 
protocol deviations are identified during routine remote data review. 
 
 
Case Report Forms and Source Documentation  
11.3.
All data obtained during this study must be entered in the e-CRFs in a timely fashion (within 30 
days). All source documents from which e-CRF entries are derived should be filed in the patient’s 
study chart. 
 
Site personnel will receive training on the e-CRF and the specific procedures to be used for data 
entry and query resolution. 
 
 Data Collection  
11.3.1.
The Investigators (and appropriately authorized staff) will be given access to an online web-based 
EDC system. This system is specifically designed for the collection of the clinical data in electronic 
format. Access and rights to the EDC system will be carefully controlled and configured according 
to each individual’s role throughout the study. In general, only the Investigator and authorized 
staff will be able to enter data and make corrections in the e-CRFs. 
 

 
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The e-CRF should be completed for each subject for whom the study-specific ICF was obtained and 
should reflect the latest observations on the subject participating in the study. 
 
Therefore, the e-CRFs are to be completed as soon as possible after the data is collected (with a 
maximum delay of 30 days). The Investigator must verify that all data entries in the e-CRF are 
accurate and correct. If some assessments cannot be done, or if certain information is unavailable, 
not applicable or unknown, the Investigator should indicate this in the e-CRF. 
 
After completion, the Investigator will be required to validate and electronically sign-off the 
clinical data recorded in each e-CRF. 
 
Information concerning investigational product dispensation to the subject will be tracked in the 
e-CRF. 
 
 
Access to Source Data 
11.4.
 Remote Monitoring 
11.4.1.
Considering the current context of pandemic, during the study, a site monitor will conduct remote 
monitoring site visits to review protocol compliance, compare e-CRF entries and individual 
subject’s medical records (source verification), assess investigational product accountability, and 
ensure that the study is being conducted according to ethical and pertinent regulatory 
requirements. The e-CRF entries will be verified with source documentation. The review of 
medical records will be performed in a manner to ensure that subject confidentiality is 
maintained. 
 
Checking of the e-CRF entries for completeness and clarity, and cross-checking with source 
documents, will be required to monitor the progress of the study. Access to source data will be 
required for the monitoring activities. Source documents will be scanned and sent through a 
secure email. In both cases, the copies received will be destroyed by the monitor after their 
review. All source documents will be anonymized (names will be removed and replaced with the 
subject’s study ID number at the site level) prior to being sent to the study monitor. 
 
 Inspection and Audit Procedures  
11.4.2.
The Sponsor or its representative may conduct audits at the investigative sites including, but not 
limited to, investigational product supply, presence of required documents, the informed consent 
process, and comparison of e-CRFs with source documents. All medical records (progress notes) 
must be available for audit. The Investigator agrees to participate in audits conducted at a 
convenient time in a reasonable manner. 
 
Moreover, local Regulatory Authorities may wish to carry out such source data checks and/or on-
site inspections. Direct access to source data will be required for these inspections; they will be 
carried out giving due consideration to data protection and medical confidentiality. 
 
 

 
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Data Processing 
11.5.
All data will be entered by authorized site personnel into the e-CRF. The data-review and data-
handling document will include specifications for consistency and plausibility checks on data and 
will also include data-handling rules for obvious data errors. Queries/inconsistencies will be sent 
to the study Investigators and monitors for resolution. The database will be updated on the basis 
of validated/signed corrections. 
 
Previous and concomitant medications will be coded using the WHO Drug Reference List, which 
employs the Anatomical Therapeutical Chemical classification system. Disease and Medical 
histories/current medical conditions and AEs will be coded using MedDRA. The CTCAE v4.0 will be 
used to support investigator severity grading. The versions of the coding dictionaries will be 
provided in the Clinical Study Report. 
 
 
Archiving Study Records  
11.6.
All data derived from the study will remain the property of the Sponsor. Records must be retained 
in accordance with the current International Conference on Harmonization (ICH) Guidelines on 
GCP. All essential study documents including records of subjects, source documents, e-CRFs and 
investigational product inventory must be kept in a study specific file. The Investigator site files 
must be retained by the Investigator at least 25 years after the completion of the trial. 
 
Subjects’ medical records must be kept for the maximum period permitted by the hospital, 
institution or private practice. 
 
The Investigator will not discard any relevant records to this study without prior written 
permission from the Sponsor. The Investigator shall notify the Sponsor in writing of their intent to 
destroy all such material. The Sponsor shall have 30 days to respond to the Investigator’s notice 
and the Sponsor shall have a further opportunity to retain such materials at the Sponsor’s 
expense. 
 
The Investigator shall take responsibility for maintaining adequate and accurate source documents 
(hard copy or electronic) of all observations and data generated during this study. Such 
documentation is subject to inspection by the Sponsor, its representatives and Regulatory 
Authorities. If an Investigator moves, withdraws from the study or retires, the responsibility for 
maintaining the records may be transferred to another person who will accept responsibility. 
Notice of transfer must be made to and agreed by the Sponsor. 
 
 
Good Clinical Practice  
11.7.
The procedures set out in this study protocol are designed to ensure that the Sponsor and 
Investigators abide by the principles of the ICH-GCP Guidelines, and of the Declaration of Helsinki 
(Appendix 1). The study will also be carried out in keeping with local legal requirements. 
 
 

 
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Protocol Approval and Amendment  
11.8.
Before the start of the study, the study protocol and/or other relevant documents will be 
reviewed and approved by the REB/IRB/IEC/Regulatory Authorities, in accordance with local legal 
requirements. The Sponsor must ensure that all ethical and legal requirements have been met 
before the first subject is enrolled in the study. 
 
This protocol is to be followed exactly. Any change to the protocol must be handled as a protocol 
amendment. Any potential amendment must be approved by the Sponsor. A written amendment 
must be submitted to the appropriate Regulatory Authorities and to the REB/IRB/IECs assuming 
this responsibility. The Investigator must await REB/IRB/IEC approval of protocol amendments 
before implementing the changes, except where necessary to eliminate apparent immediate 
hazard to subjects. 
 
All substantial amendments to the protocol must be approved in writing by both the appropriate 
Regulatory Authorities and the REB/IRB/IEC, except for administrative amendments, which require 
notification or protocol addendums but not written approval or modifications that are subject to 
the Health Canada interim order for clinical trials on COVID-19 issued June 2nd 2020. Once 
approved, the protocol amendment will be distributed to all recipients of the original protocol, 
with instructions to append the amendment to the protocol. If, in the judgment of the local 
REB/IRB/IEC, the Investigator and/or Sponsor, the protocol amendment alters the study design, 
procedures and/or increases the potential risk to the subject, the currently approved written ICF 
will require modifications. 
 
The modified ICF must also be reviewed and approved by the Sponsor, appropriate Regulatory 
Authorities, and the REB/IRB/IEC. In such cases, repeat informed consent must be obtained from 
the enrolled subjects or parents/guardians before participation continues. 
 
 
Duration  of the Study  
11.9.
For an individual subject, study ends for a subject 89 days after randomization (except for 
pregnant women on the CCP arm, which should be followed until pregnancy outcome is known). 
The overall study will end when the last randomized subject has reached the Day 90 time point. 
The inclusion of new participants will be determined based on new data and clinical needs 
according to the evolution of the pandemic. The planned study duration is 1 year.  
 
 
Premature Termination of the Study  
11.10.
If the Investigator, the Sponsor, or the Medical Monitor becomes aware of conditions or events 
that suggest a possible hazard to subjects if the study continues, the study may be terminated 
after appropriate consultation between the relevant parties. The study may also be terminated 
early at the Sponsor’s discretion in the absence of such a finding. 
 
Conditions that may warrant termination include, but are not limited to: 
1. Concern regarding an unacceptable risk to subjects 
2. Results of interim analysis demonstrate superiority  

 
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59 
3. Results of the interim analysis for the revised sample size makes the resultant study 
infeasible due to the large number of patients required 
4. Insufficient compliance to protocol requirements 
5. Data that are not sufficiently complete and/or are not evaluable 
6. Regulatory authorities recommend termination of the study 
7. Novel scientific data on the efficacy or safety of COVID-19 convalescent plasma is published 
during the conduct of the trial that raise concerns regarding the safety of CCP 
 
In terminating the study, the Sponsor and the Investigators will ensure that adequate 
consideration is given to the protection of the subjects’ interests. 
 
 
Confidentiality 
11.11.
All information obtained during the conduct of the study with respect to the subject’s state of 
health will be regarded as confidential. For disclosure of any such information, an agreement will 
be obtained in writing. The Investigator must ensure that each subject’s anonymity is maintained. 
On e-CRFs and other documents transmitted to the Sponsor or its representatives, subjects must 
not be identified by name. Instead, subjects will only be known by the unique subject screening 
number allocated to them in order to ensure confidentiality on all study documentation. Subjects 
will retain this unique number throughout the study. The Investigator will keep a separate log of 
these codes. 
 
In order to comply with government regulatory guidelines and to ensure subject safety, it may be 
necessary for the Sponsor and its representative, the REB/IRB/IEC or Regulatory Authorities to 
review subjects’ medical records as they relate to this study. Only the subject’s unique number in 
the e-CRFs will identify her/him, but their full names may be made known to a Regulatory 
Authority or other authorized government or health care officials, if necessary, and to personnel 
designated by the Sponsor. 
 
Documents that are not for submission to the Sponsor (for example consent forms) will be 
maintained by the Investigator in strict confidence, except to the extent necessary to allow 
monitoring and auditing by the Sponsor and inspection by Regulatory Authorities. No documents 
identifying subjects by name will leave the investigative site and subject identity will remain 
confidential in all publications related to the study. 
 
 
Publication Policy  
11.12.
By signing the study protocol, the Investigator agrees with the use of results of the study for the 
purposes of national and international registration, publication and information for medical and 
pharmaceutical professionals. If necessary, Regulatory Authorities will be notified of the 
Investigator’s name, address, qualifications and extent of involvement. The Investigator shall not 
publish any data (poster, abstract, paper, etc.) without having consulted with the Sponsor in 
advance and having received a written approval for such a publication. The sponsor-investigator 
will be responsible for publication of the data.  
 

 
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60 
The sponsor-investigator must commit to publish and disseminate the study results in a timely 
manner without excessive restriction, regardless of whether the initial study hypothesis is 
confirmed or not.  
 
 
 
Critical Documents 
11.13.
Before the Investigator starts the trial, the following documents must be provided to the site from 
the sponsor: 
 
1. Regulatory approval (Health Canada NOL)(FDA in U.S. site) (CONEP in Brazil) (Meir Medical 
Centre Helsinki Committee in Israel); 
2. Protocol, any substantial amendments; 
3. Subject information/informed consent form; 
4. Any other written information to be provided to the subject; 
5. Subject recruitment procedures; 
6. Templates for Delegation of Authority, CTSI form, Qualified Investigator Form and Health 
Canada REB Attestation where applicable. 
7. Study procedures documents: SOPs/Operations Manual, eCRF system setup. 
8. SAE reporting procedure for the study 
 
These documents must be collected from site in order to begin recruitment and subject 
enrollment: 
 
1. Curricula vitae of Investigator and Sub-investigator(s) (current, dated and signed); 
2. Favourable opinion from REB/IRB/IEC clearly identifying the documents reviewed; 
3. Subject recruitment procedures that have not been identified by the protocol; 
4. List of REB/IRB/IEC members and constitution; 
5. Signed and dated agreement on the final protocol; 
6. Signed and dated agreement on any substantial amendment(s), if applicable; 
7. Copy of REB/IRB/IEC approved subject information/informed consent form; 
8. Written information/advertisement; 
9. Receipt of the Circular of Information/Notice d’accompagnement signed by Investigator 
(where applicable); 
10. Laboratory certification and normal ranges; 
11. Financial agreement(s). 
12. Copy of completed Delegation of Authority 
 
 
Clinical Study Report 
11.14.
Final clinical study reports will be prepared according to the ICH guideline on Structure and 
Contents of Clinical Study Reports. It will be prepared regardless of whether the study is 
completed or prematurely terminated. The Sponsor will provide each Investigator with a copy of 
the final report for retention. 
 
 

 
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61 
 STATISTICAL CONSIDERATIONS 
12.
 
Sample Size Considerations 
12.1.
Assuming a baseline risk of intubation or death by Day 30 of 30% in hospitalized patients with 
standard of care, a sample size of 1200 (800 in the CCP arm, and 400 in the standard of care arm) 
would provide 80% power to detect a relative risk reduction of 25% with CCP therapy using a 2-
tailed test at level α = 0.05. This assumes no patient is lost to follow-up. Lost follow-up is expected 
to be minimal.  
 
There is uncertainty about the intubation and mortality rate that will be observed in this study due 
to possibly evolving profile of COVID-19 patients admitted hospital over the course of the 
pandemic. To address this, a blinded sample-size re-estimation will take place when the primary 
outcome is available for 50% of the target sample. Sample size will only be adjusted if the 
estimated event rate is different than the originally specified event rate to a sufficient extent that 
the study is not expected to achieve the desired nominal power for the test of the primary 
outcome. 
 
 
Planned Interim Analyses 
12.2.
A single interim analysis is planned when information on intubation or death at Day 30 is available 
for 50% of the target sample. An O'Brien-Fleming stopping rule will be employed.44 
 
The IDSMC may recommend early termination or modification of the protocol only when there is 
clear and substantial evidence of a treatment difference. More details about the interim analyses 
are described below as well as a separate guidance document for the IDSMC.  
 
 Safety Review 
12.2.1.
Safety analyses will evaluate serious AEs by treatment. The unblinded independent statistician will 
prepare these reports for review by the IDSMC. The IDSMC will review data on the occurrence of 
all reportable AEs at each of their meetings to ensure there are not significant numbers of 
unexpected AEs (AEs that do not fit with the known course of COVID-19, based on emerging data 
from the published and unpublished literature). If there is a significant number of unexpected AEs, 
the IDSMC will be asked to review unblinded safety data in an ad hoc meeting. Regular safety 
reports will be created to provide descriptive statistics on the occurrence of AEs to the IDSMC. The 
IDSMC may request safety data in a blinded or unblinded fashion as per their discretion. 
 
 
 Efficacy Review 
12.2.2.
A single interim analysis is planned when information on the primary outcome (composite of 
intubation or death at Day 30) are available for 50% of the target sample. The Lan-DeMets 
spending function54 analog of the O’Brien-Fleming boundaries44 will be used to monitor the 
primary endpoint as a guide for the DSMB for an overall two-sided type-I error rate of 0.05. 
Conditional power will be presented as an additional guide to the DSMB. Conditional power allows 

 
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62 
computation of the probability of obtaining a statistically significant result by the end of the trial 
given the data accumulated thus far, incorporating a hypothesized treatment effect (e.g., the 
treatment effect assumed for sample size determination) thereafter. If conditional power is less 
than 20% under the original trial assumptions, consideration could be given to stopping the trial. 
An unblinded independent statistician will prepare the reports for IDSMC to review when making 
their recommendations. An IDSMC charter will further describe procedures and membership. An 
additional document on statistical methods related to the interim analyses will be provided to the 
IDSMC prior to their first meeting.  
 
An additional document on statistical issues related to monitoring will be provided to the IDSMC 
prior to interim analyses. 
 
 
 
Stopping Rules 
12.3.
If there are a concerning number of unexpected AEs, the IDSMC will be asked to review safety data 
in an ad hoc meeting. This study may be prematurely terminated if there is reasonable cause, 
including but not limited to: determination of unexpected, significant, or unacceptable risk to 
subjects; results of interim analysis; insufficient compliance to protocol requirements; data that are 
not sufficiently complete and/or not evaluable.  If the study is prematurely terminated, the site 
Qualified Investigator will promptly inform study subjects and the REB as applicable. The site PI will 
assure appropriate follow-up for the subjects, as necessary. The sponsor will notify regulatory 
authorities as applicable. If there are a concerning number of unexpected AEs, the IDSMC will be 
asked to review all safety data in an ad hoc meeting.  
 
This study may be prematurely terminated by the IDSMC and/or co-principal investigators and/or 
Sponsor if there is sufficient reasonable cause (see section 11.10)  
 
 
Final Analysis Plan 
12.4.
The primary analysis will be based on the intention-to-treat population which will include data 
from all individuals who have been randomized. Outcomes will be attributed to the arm to which 
individuals were randomized irrespective of whether they received the planned intervention (e.g. 
plasma from a convalescent COVID-19 donor). 
 
A  per protocol analysis will also be performed. The per protocol sample will be comprised of 
eligible individuals who are randomized and are treated according to the protocol. In this trial, 
patients will be excluded from the per protocol analysis if any of the following protocol violations 
occur: 
-patient received less than two units of CCP 
-transfusion of second unit of CCP completed more than 24 hours after randomization (special 
consideration will be given for instances where 1 x 500 mL unit was given)  
-patient was randomized to  SOC  but received CCP 

 
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63 
-patient was randomized despite being ineligible for the trial 
 Primary Efficacy Endpoint 
12.4.1.
Intubation or death at Day 30 is the primary endpoint. 
 
Given the fact that the times from admission to discharge or death are expected to be relatively 
short, we are using a binary response indicating intubation or death at Day 30. The primary 
analysis will therefore be based on a 2-sided Wald test of the null hypothesis that probability of 
intubation or death is the same among individuals receiving CP or standard of care. The relative 
risk reduction for death (CCP versus standard of care) will be computed along with a 95% 
confidence interval. 
  
Efforts to minimize loss-to-follow-up will be considerable and we are expected to have complete 
data on individuals for the primary outcome. 
 
Sensitivity analyses will evaluate the impact of making different assumptions about missing data 
for secondary outcomes. These sensitivity analyses will be fully defined in the statistical analysis 
plan (SAP). 
 
 Secondary Endpoints 
12.4.2.
A cause-specific Cox regression model will be fitted for the intubation-free survival time defined as 
the first of the times of intubation or death with censoring at discharge or 30 days whichever 
comes first. A hazard ratio and 95% confidence interval will be computed from this fitted model.  
 
Cumulative incidence functions will be estimated and plotted for each treatment arm for the time 
to intubation or death. 
 
The restricted mean number of ventilator-free days over the first 30 days will be compared 
between the two groups based on a nonparametric tests.  
 
The time to in-hospital death will be analyzed using a cause-specific Cox regression model treating 
the minimum of the time of discharge and 90 days as the censoring time. A hazard ratio and 95% 
confidence interval will be computed from this fitted model. Cumulative incidence functions will 
be estimated and plotted to estimate the proportion of patients who died during the initial 
hospitalization up to 90 days from randomization.   
 
Finally, the survival status of individuals will be recorded at day 30 and the proportion of 
individuals who have died will be computed for each arm with a two-sample Wald test carried out 
based on the proportions. 
  
Length of hospitalization over 90 days and length of stay in the ICU over 30 days will be modeled 
using a Cox regression without any distinction between reasons for discharge. 
 

 
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The proportion of patients needing ECMO over 30 days will be compared between the two arms 
based on a two-sided test of the difference between proportions.  
 
The proportion of patients needing renal replacement therapy over the first 30 days will be 
compared between the two arms based on a Wald test.  
 
The proportion of patients developing myocarditis over the first 30 days will be compared 
between the two arms based on a Wald test.  
 
The change in EQ-5D-5L utility value from baseline will be compared between the two arms. 
 
Incremental cost per quality-adjusted life year between the CCP and standard care over the 30-day 
time horizon.  
 
No multiplicity adjustments will be implemented for the secondary analyses. Procedures for 
addressing missing data will be described in the SAP.  
 
 
 Safety Analysis 
12.4.3.
Safety endpoints include death through Day 30, SAEs, and severe AEs. These events will be 
analyzed univariately and as a composite endpoint. Time-to-event methods will be used for death 
and the composite endpoint. Each AE will be counted once for a given participant and graded by 
severity and relationship to COVID-19 or study intervention. AEs will be presented by system organ 
class, duration (in days), start and stop-date. AEs leading to premature discontinuation from the 
study intervention and serious treatment-emergent AEs should be presented either in a table or a 
listing. Counts of the number of individuals experiencing SAEs and severe AEs will be tabulated by 
event type and treatment group. They will then be tabulated by organ system, duration (in days), 
start and stop-date.  Then the total number of events of each type will be summarized by group, 
allowing for each individual to contribute a count response for the number of AEs. 
 
Each AE will also be characterized in terms of its relationship with COVID-19 or the current study 
intervention. The occurrence of transfusion associated AEs will likewise be compared between the 
two groups based on proportions. 
 
Co-enrollment in other clinical trials is allowed in this protocol so we will record the nature of the 
interventions in these other trials and, if possible, the particular intervention to which our study 
participants were assigned. 
  
Cox regression models will also be fitted for the time to the first of each SAE and severe AE to deal 
with the fact that death and discharge are censoring events.  
  
AEs leading to premature discontinuation from the study intervention and serious treatment-
emergent AEs will be tabulated or presented as a listing. 
 

 
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65 
 Sub-Group Analysis 
12.4.4.
Subgroup analyses for the primary outcomes will evaluate the treatment effect across the 
following subgroups:  
 Patients enrolled vs. not enrolled/treated in other therapeutic clinical trials 
 >= 60 years versus less than 60 years of age 
 Sex 
 Ethnicity 
o White/Black/Hispanic/Asian/Other   
 Presence of medical co-morbidities  
o diabetes (yes/no) 
o cardiac (yes/no)  
o respiratory (yes/no) 
 Smoking History 
o Ever smoker/current smoker/never 
o 15 pack year history of smoking versus not 
 Obesity (BMI >= 30 vs <30) 
 Onset of symptoms > 12 days before randomization (including non-respiratory symptoms) 
versus not 
 Timing of administration of CCP from diagnosis of COVID-19 (<=72 hours vs >72 hours) 
 Severity of illness of donors (hospitalized vs not) 
 ABO blood type of recipients (A vs other, B vs other, O vs other, AB vs other) 
 CCP from one donor vs CCP from two donors 
 Detectable vs non-detectable viral plasma viral load at baseline 
 Anti-SARS-CoV-2 seropositivity at baseline 
 Oxygen status at baseline (≤ 2L vs > 2L) 
 
A forest plot will display confidence intervals across subgroups. Interaction tests will be conducted 
to determine whether the effect of treatment varies by subgroup. 
 
 Exploratory Analysis 
12.4.5.
 
Association between anti-SARS-CoV2 antibody  in CCP and the primary outcome of intubation or 
death will be assessed using logistic regression. Anti-SARS-CoV-2 antibodies will be characterized 
according to the amount of antibodies against the native spike protein and the RBD, as well as to 
their neutralizing and Fc functions. Exploratory analyses will also examine possible associations 
between donor characteristics and treatment efficacy. Change in viral load and in anti-SARS-CoV2 
serology in the recipient following transfusion will also be assessed and correlated with treatment 
outcome. 
 
 
 
 

 
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66 
 LIST OF APPENDICES 
13.
 
APPENDIX 1:   
Declaration of Helsinki 
 
APPENDIX 2:  
Steering Committee Members 
 
 
 
 
 

 
CONCOR-1 Protocol 15 January 2021 v8.0    
67 
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APPENDIX 1 : Declaration of Helsinki 
 
WMA DECLARATION OF HELSINKI   
ETHICAL PRINCIPLES FOR MEDICAL RESEARCH INVOLVING HUMAN SUBJECTS 
 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 
and amended by the: 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
53rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification added) 
55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added) 
59th WMA General Assembly, Seoul, Republic of Korea, October 2008 
64th WMA General Assembly, Fortaleza, Brazil, October 2013 
Preamble 
1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of 
ethical principles for medical research involving human subjects, including research on identifiable 
human material and data. 
The Declaration is intended to be read as a whole and each of its constituent paragraphs should be applied 
with consideration of all other relevant paragraphs. 
2. Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians. The 
WMA encourages others who are involved in medical research involving human subjects to adopt these 
principles. 
General Principles 
3. The Declaration of Geneva of the WMA binds the physician with the words, “The health of my patient 
will be my first consideration,” and the International Code of Medical Ethics declares that, “A physician 
shall act in the patient’s best interest when providing medical care.” 
4. It is the duty of the physician to promote and safeguard the health, well-being and rights of patients, 
including those who are involved in medical research. The physician’s knowledge and conscience are 
dedicated to the fulfilment of this duty. 
5. Medical progress is based on research that ultimately must include studies involving human subjects. 
6. The primary purpose of medical research involving human subjects is to understand the causes, 
development and effects of diseases and improve preventive, diagnostic and therapeutic interventions 
(methods, procedures and treatments). Even the best proven interventions must be evaluated 
continually through research for their safety, effectiveness, efficiency, accessibility and quality. 
7. Medical research is subject to ethical standards that promote and ensure respect for all human subjects 
and protect their health and rights. 
8. While the primary purpose of medical research is to generate new knowledge, this goal can never take 
precedence over the rights and interests of individual research subjects. 

 
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9. It is the duty of physicians who are involved in medical research to protect the life, health, dignity, 
integrity, right to self-determination, privacy, and confidentiality of personal information of research 
subjects. The responsibility for the protection of research subjects must always rest with the physician 
or other health care professionals and never with the research subjects, even though they have given 
consent. 
10. Physicians must consider the ethical, legal and regulatory norms and standards for research involving 
human subjects in their own countries as well as applicable international norms and standards. No 
national or international ethical, legal or regulatory requirement should reduce or eliminate any of the 
protections for research subjects set forth in this Declaration. 
11. Medical research should be conducted in a manner that minimizes possible harm to the environment. 
12. Medical research involving human subjects must be conducted only by individuals with the appropriate 
ethics and scientific education, training and qualifications. Research on patients or healthy volunteers 
requires the supervision of a competent and appropriately qualified physician or other health care 
professional. 
13. Groups that are underrepresented in medical research should be provided appropriate access to 
participation in research. 
14. Physicians who combine medical research with medical care should involve their patients in research 
only to the extent that this is justified by its potential preventive, diagnostic or therapeutic value and if 
the physician has good reason to believe that participation in the research study will not adversely affect 
the health of the patients who serve as research subjects. 
15. Appropriate compensation and treatment for subjects who are harmed as a result of participating in 
research must be ensured. 
Risks, Burdens and Benefits 
16. In medical practice and in medical research, most interventions involve risks and burdens. 
Medical research involving human subjects may only be conducted if the importance of the objective 
outweighs the risks and burdens to the research subjects. 
17. All medical research involving human subjects must be preceded by careful assessment of predictable 
risks and burdens to the individuals and groups involved in the research in comparison with foreseeable 
benefits to them and to other individuals or groups affected by the condition under investigation. 
Measures to minimize the risks must be implemented. The risks must be continuously monitored, assessed 
and documented by the researcher. 
18. Physicians may not be involved in a research study involving human subjects unless they are confident 
that the risks have been adequately assessed and can be satisfactorily managed. 
When the risks are found to outweigh the potential benefits or when there is conclusive proof of definitive 
outcomes, physicians must assess whether to continue, modify or immediately stop the study. 
Vulnerable Groups and Individuals 
19. Some groups and individuals are particularly vulnerable and may have an increased likelihood of being 
wronged or of incurring additional harm. 

 
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All vulnerable groups and individuals should receive specifically considered protection. 
20. Medical research with a vulnerable group is only justified if the research is responsive to the health 
needs or priorities of this group and the research cannot be carried out in a non-vulnerable group. In 
addition, this group should stand to benefit from the knowledge, practices or interventions that result 
from the research. 
Scientific Requirements and Research Protocols 
21. Medical research involving human subjects must conform to generally accepted scientific principles, be 
based on a thorough knowledge of the scientific literature, other relevant sources of information, and 
adequate laboratory and, as appropriate, animal experimentation. The welfare of animals used for 
research must be respected. 
22. The design and performance of each research study involving human subjects must be clearly described 
and justified in a research protocol. 
The protocol should contain a statement of the ethical considerations involved and should indicate how the 
principles in this Declaration have been addressed. The protocol should include information regarding 
funding, sponsors, institutional affiliations, potential conflicts of interest, incentives for subjects and 
information regarding provisions for treating and/or compensating subjects who are harmed as a 
consequence of participation in the research study. 
In clinical trials, the protocol must also describe appropriate arrangements for post-trial provisions. 
Research Ethics Committees 
23. The research protocol must be submitted for consideration, comment, guidance and approval to the 
concerned research ethics committee before the study begins. This committee must be transparent in 
its functioning, must be independent of the researcher, the sponsor and any other undue influence and 
must be duly qualified. It must take into consideration the laws and regulations of the country or 
countries in which the research is to be performed as well as applicable international norms and 
standards, but these must not be allowed to reduce or eliminate any of the protections for research 
subjects set forth in this Declaration. 
The committee must have the right to monitor ongoing studies. The researcher must provide monitoring 
information to the committee, especially information about any serious AEs. No amendment to the 
protocol may be made without consideration and approval by the committee. After the end of the study, 
the researchers must submit a final report to the committee containing a summary of the study’s findings 
and conclusions. 
Privacy and Confidentiality 
24. Every precaution must be taken to protect the privacy of research subjects and the confidentiality of 
their personal information. 
 
Informed Consent 
25. Participation by individuals capable of giving informed consent as subjects in medical research must be 
voluntary. Although it may be appropriate to consult family members or community leaders, no 
individual capable of giving informed consent may be enrolled in a research study unless he or she freely 
agrees. 

 
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26. In medical research involving human subjects capable of giving informed consent, each potential subject 
must be adequately informed of the aims, methods, sources of funding, any possible conflicts of 
interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the 
study and the discomfort it may entail, post-study provisions and any other relevant aspects of the 
study. The potential subject must be informed of the right to refuse to participate in the study or to 
withdraw consent to participate at any time without reprisal. Special attention should be given to the 
specific information needs of individual potential subjects as well as to the methods used to deliver the 
information. 
After ensuring that the potential subject has understood the information, the physician or another 
appropriately qualified individual must then seek the potential subject’s freely-given informed consent, 
preferably in writing. If the consent cannot be expressed in writing, the non-written consent must be 
formally documented and witnessed. 
All medical research subjects should be given the option of being informed about the general outcome and 
results of the study. 
27. When seeking informed consent for participation in a research study the physician must be particularly 
cautious if the potential subject is in a dependent relationship with the physician or may consent under 
duress. In such situations the informed consent must be sought by an appropriately qualified individual 
who is completely independent of this relationship. 
28. For a potential research subject who is incapable of giving informed consent, the physician must seek 
informed consent from the legally authorized representative. These individuals must not be included in 
a research study that has no likelihood of benefit for them unless it is intended to promote the health of 
the group represented by the potential subject, the research cannot instead be performed with persons 
capable of providing informed consent, and the research entails only minimal risk and minimal burden. 
29. When a potential research subject who is deemed incapable of giving informed consent is able to give 
assent to decisions about participation in research, the physician must seek that assent in addition to 
the consent of the legally authorized representative. The potential subject’s dissent should be 
respected. 
30. Research involving subjects who are physically or mentally incapable of giving consent, for example, 
unconscious patients, may be done only if the physical or mental condition that prevents giving 
informed consent is a necessary characteristic of the research group. In such circumstances the 
physician must seek informed consent from the legally authorized representative. If no such 
representative is available and if the research cannot be delayed, the study may proceed without 
informed consent provided that the specific reasons for involving subjects with a condition that renders 
them unable to give informed consent have been stated in the research protocol and the study has been 
approved by a research ethics committee. Consent to remain in the research must be obtained as soon 
as possible from the subject or a legally authorized representative. 
31. The physician must fully inform the patient which aspects of their care are related to the research. The 
refusal of a patient to participate in a study or the patient’s decision to withdraw from the study must 
never adversely affect the patient-physician relationship. 
32. For medical research using identifiable human material or data, such as research on material or data 
contained in biobanks or similar repositories, physicians must seek informed consent for its collection, 
storage and/or reuse. There may be exceptional situations where consent would be impossible or 

 
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impracticable to obtain for such research. In such situations the research may be done only after 
consideration and approval of a research ethics committee. 
Use of Placebo 
33. The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the 
best proven intervention(s), except in the following circumstances: 
Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or 
Where for compelling and scientifically sound methodological reasons the use of any intervention less 
effective than the best proven one, the use of placebo, or no intervention is necessary to determine the 
efficacy or safety of an intervention and the patients who receive any intervention less effective than the 
best proven one, placebo, or no intervention will not be subject to additional risks of serious or irreversible 
harm as a result of not receiving the best proven intervention. 
Extreme care must be taken to avoid abuse of this option. 
Post-Trial Provisions 
34. In advance of a clinical trial, sponsors, researchers and host country governments should make 
provisions for post-trial access for all participants who still need an intervention identified as beneficial 
in the trial. This information must also be disclosed to participants during the informed consent process. 
Research Registration and Publication and Dissemination of Results 
35. Every research study involving human subjects must be registered in a publicly accessible database 
before recruitment of the first subject. 
36. Researchers, authors, sponsors, editors and publishers all have ethical obligations with regard to the 
publication and dissemination of the results of research. Researchers have a duty to make publicly 
available the results of their research on human subjects and are accountable for the completeness and 
accuracy of their reports. All parties should adhere to accepted guidelines for ethical reporting. Negative 
and inconclusive as well as positive results must be published or otherwise made publicly available. 
Sources of funding, institutional affiliations and conflicts of interest must be declared in the publication. 
Reports of research not in accordance with the principles of this Declaration should not be accepted for 
publication. 
Unproven Interventions in Clinical Practice 
In the treatment of an individual patient, where proven interventions do not exist, or other known 
interventions have been ineffective, the physician, after seeking expert advice, with informed consent from 
the patient or a legally authorized representative, may use an unproven intervention if in the physician’s 
judgement it offers hope of saving life, re-establishing health or alleviating suffering. This intervention 
should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all 
cases, new information must be recorded and, where appropriate, made publicly available. 
 
 
 

 
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APPENDIX 2: Steering Committee  
Co-Principal Investigators 
Donald Arnold 
arnold@mcmaster.ca 
Director of the McMaster Centre for Transfusion Research 
Associate Professor, Division of Hematology and 
Thromboembolism, Department of Medicine, McMaster University 
Philippe Begin 
philippe.begin@umontreal.ca 
Associate Professor, Department of Medicine, Université de Montréal 
Director, Oral Immunotherapy Clinic (CITO), CHU Sainte-Justine 
Immuno-Allergist, CHU Sainte-Justine 
Researcher, CHU Sainte-Justine 
 
Steering Committee 
Alan Tinmouth 
atinmouth@toh.ca 
Transfusion 
Medicine 
Director, OHRI Centre for Transfusion Research, 
Clinical Epidemiology Program, Ottawa Hospital 
Research Institute; Associate Professor, Hematology, 
University of Ottawa 
Jeannie Callum 
jeannie.callum@sunnybrook.ca 
Transfusion 
Medicine 
Lead for the QUEST University of Toronto Transfusion 
Research Team; Professor, Laboratory Medicine and 
Pathobiology 
Michelle Zeller 
zeller@mcmaster.ca 
Transfusion 
Medicine 
Assistant Professor, Division of Hematology and 
Thromboembolism, Department of Medicine, 
McMaster University 
Nancy Heddle 
heddlen@mcmaster.ca 
Methodology 
Professor Emeritus, Department of Medicine, 
McMaster University 
Richard Cook 
rjcook@uwaterloo.ca 
Statistician 
Professor, Faculty of Statistics and Actuarial Science, 
University of Waterloo 
Damon Scales 
damon.scales@sunnybrook.ca 
Intensivist 
Methodologist 
Chief, Department of Critical Care Medicine, 
Sunnybrook Health Sciences Centre; Professor, 
Department of Medicine, interdepartmental division 
of critical care, University of Toronto 
Alison McGeer 
Allison.McGeer@sinaihealth.ca 
Infectious 
Diseases 
Professor, Departments of Laboratory Medicine and 
Pathobiology and Public Health Sciences, University of 
Toronto; Director of Infection Control, Mount Sinai 
Hospital 
Dana Devine 
dana.devine@blood .ca 
Transfusion 
Scientist  
Chief Medical & Scientific Officer, Canadian Blood 
Services; Professor, Pathology and Laboratory 
Medicine, Medicine 
Lisa Schwartz 
schwar@mcmaster.ca 
Statistician 
Ethicist 
Associate Professor, Department of Clinical 
Epidemiology & Biostatistics, Faculty of Health 
Sciences, McMaster University 
Dean Ferguson 
dafergusson@ohri.ca 
Methodologist 
Senior Scientist, Clinical Epidemiology Program, 
Ottawa Hospital Research Institute; Director, Clinical 
Epidemiology Program, Ottawa Hospital Research 
Institute; Professor, Departments of Medicine, 
Surgery, & the School of Epidemiology and Public 
Health, University of Ottawa 
Richard Carl 
richardcarl@sympatico.ca 
 
Patient 
Patient representative; Director of several 
corporations (Oil and gas and financial services; risk 
management) 
Ryan Zarychanski 
rzarychanski@cancercare.mb.ca 
Critical Care 
Medicine and 
Assistant Professor and Clinician-Scientist at the 
University of Manitoba in the Department of 

 
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Hematology 
Medicine, Sections of Critical Care and of 
Hematology/Medical Oncology 
Renee Bazin 
Renee.bazin@hema-quebec.qc.ca  
Scientist,  Hema 
Quebec 
Associate Professor in the Department of Biochemistry 
and Microbiology and in the Faculty of Pharmacy at 
Laval University. Director of Medical Affairs and 
Innovcation at Hema-Quebec  
Nadine Shehata  
Nadine.Shehata@sinaihealth.ca  
Hematology  
Head, Transfusion Medicine, Mount Sinai Hospital, 
Toronto.  Associate Professor,Departments of 
Medicine, 
Laboratory Medicine and Pathobiology and Institute of 
Health Policy Management & 
Evaluation, University of Toronto. Associate Scientist, 
Keenan Research Centre, Li Ka Shing Knowledge 
Institute, St Michaels Hospital.  
Alexis Turgeon 
Alexis.turgeon@crchudequebec.ulaval.ca  
Critical Care and 
Trauma  
Associate Professor and Director of research, Division 
of Critical Care Medicine and Department of 
Anesthesiology and Critical Care, Laval University.  
Nancy Robitaille 
Nancy.Robitaille.MD@hema-
quebec.qc.ca 
Pediatric 
Hematologist  
Associate Professor, Department of Pediatrics, 
Université de Montréal 
Pediatric hematologist, CHU Sainte-Justine 
Vice-president, Transfusion Medicine, Héma-Québec 
 
Michael Chassé 
michael.chasse@umontreal.ca 
Critical Care  
Intensivist, Centre Hospitalier de l’Unversite de 
Montreal (CHUM). Assistant Professor, Department of 
Medicine,  University of Montreal  
Nick Daneman 
Nick.daneman@sunnybrook.ca 
Infectious 
Disease  
Division of Infectious Diseases, Department of 
Medicine, University of Toronto; Infectious Diseases, 
Department of Medicine 
Melissa Cushing 
mec2013@med.cornell.edu 
Transfusion 
Medicine 
Transfusion Medicine and Cellular Therapy, New York-
Presbyterian; Pathology and Laboratory Medicine, 
Weill Cornell Medicine, Cornell University 
Bruce Sachais 
BSachais@nybc.org 
Transfusion and 
Apheresis 
Medicine 
Chief Medical Officer, Vice President - NYBC 
Enterprises  
Professor, Pathology and Laboratory Medicine - Weill 
Cornell Medical College 
Luiz Amorim 
luizamorimfilho@gmail.com 
Transfusion 
Medicine 
Hematology 
Director, Hemorio, Rio de Janeiro, Brazil 
 
Kent Cadogan Loftsgard 
Kent-l@usa.net 
Patient 
(Congenital 
Spastic Cerebral 
Palsy) 
Community 
Advisory 
Committee 
Representative 
Clinical Educator/Health Researcher - University of 
British Columbia/Vancouver Coastal Health/Canadian 
Institutes of Health Research, and others.  
Extensive experience includes health specialty 
broadcast & print communications production.