Pilot Study for Use of Convalescent Plasma Collected From Patients Recovered From COVID-19 Disease for Transfusion as an Empiric Treatment During the 2020 Pandemic at the University of Chicago Medical Center
Phase: EARLY_PHASE1
Conditions: Coronavirus
Sponsor: University of Chicago

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Long title:  Pilot Study for Use of Convalescent Plasma Collected from Patients 
Recovered from COVID-19 Disease for Transfusion as an Empiric Treatment during the 
2020 Pandemic at the University of Chicago Medical Center 
 
Short title: COVID-19 Convalescent plasma 
 
Conducted by: University of Chicago Medical Center 
 
Principal Investigator: Maria Lucia Madariaga, MD 
 
Co-Investigators: Chancey Christensen,MD,  Madan Kumar, MD, Micah Prochaska, 
MD   Stephen Schrantz, MD,  Patrick Wilson, MD, John Alverdy, MD, Kathleen Beavis, 
MD, Haley DuganAmy Durkin-Celauro, PA, Diego di Sabato, MD, John Fung, MD, 
Jenna Guthmiller, Maud Jansen, David Meltzer, MD,  Won Hee Oh, PA, Kumaran 
Shanmugarajah, MDDustin Shaw, Julian Solway, MD, Laura Trockman, MS, PA-C,  
Geoffrey Wool, MD, PhD, Nai Zheng, John Kress, MD 
 
Study Staff: Marina Palumbo, Farah Ahmed, Lupe Castro, Haley Dugan, Amy Durkin, 
PA, Jenna Guthmiller, Maud Jansen, Won Hee Oh, PA, Dustin Shaw, Laura Trockman, 
MS, PA-C Nai Zheng 
 
 
 
 
 

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Table of Contents 
PROTOCOL SUMMARY: .......................................................................................................... 3 
Anticipated study workflow pathway: donor subjects .............................................................. 7 
Anticipated clinical workflow pathway: recipient subjects ...................................................... 8 
List of Abbreviations .................................................................................................................... 9 
Background and scientific rationale.......................................................................................... 11 
Experience with the use of convalescent plasma against coronavirus diseases ..................... 12 
Known potential risks ................................................................................................................. 13 
Known potential benefits ............................................................................................................ 14 
Investigational plan ..................................................................................................................... 14 
Study population ......................................................................................................................... 15 
Recruitment ................................................................................................................................. 17 
Schedule of Events ...................................................................................................................... 18 
Subject Withdrawal .................................................................................................................... 20 
Treatment .................................................................................................................................... 20 
Whole blood fractions not used for convalescent plasma ........ Error! Bookmark not defined. 
Rationale for doses ...................................................................................................................... 21 
Statistical considerations ............................................................................................................ 22 
Endpoints ..................................................................................................................................... 23 
Study procedures for plasma donors ........................................................................................ 24 
Study procedures for plasma recipient ..................................................................................... 24 
Efficacy and virology measures ................................................................................................. 26 
Risks and benefits ....................................................................................................................... 26 
Safety measures ........................................................................................................................... 27 
Safety Oversight .......................................................................................................................... 31 
Ethics/Protection of human subjects ......................................................................................... 33 
References .................................................................................................................................... 37 
 
 
 

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PROTOCOL SUMMARY: 
 
 
Sample Size: Total sample size = 160 subjects.  We expect to recruit 150donors and 
10 recipient subjects of convalescent plasma (CP). The donor subject number is 
because plasma received from the donors will also be screened for HLA alloantibody 
and ABO compatibility according to routine blood bank guidelines. The recipient subject 
number is to ensure the feasibility of the protocol.  
  
Study Population: Recipient subjects will be hospitalized patients aged 18 years or 
older with severe or life-threatening COVID-19 disease within 21 days or less from 
beginning of illness.  Donor subjects will be people aged 18 years or older who are able 
to donate blood per standard blood bank guidelines; have prior diagnosis of COVID-19 
documented by a laboratory test; and have complete resolution of symptoms at least 28 
days prior to donation. 
 
Study Duration: April 1, 2020 to December 31, 2022 
 
Study Design: This a prospective open label pilot study to assess the feasibility of 
delivering anti-SARS-CoV-2 convalescent plasma to hospitalized patients aged 18 
years of age or older, with severe or life-threatening COVID-19 disease less than 21 
days from the beginning of their illness.  We plan a targeted recruitment of 100 total 
eligible donor to donate plasma.  A total of 10 eligible recipient subjects will receive anti-
SARS-CoV-2 plasma after eIND application to the FDA has been approved for each 
individual subject.   
  
The following will be assessed in all donor subjects 
 
• Biomarker tests performed in the research lab (e.g. antibody titer, cytokine levels) 
• Donor questionnaire 
• Donors screened as above must be otherwise eligible, give consent, and 
successfully donate plasma, as part of a whole blood (WB)  
The following will be assessed in all recipient subjects: 
• Feasibility: is plasma given to the recipient 
• All demographic and clinical data contained in the electronic medical record, as 
well as hospital administrative data for enrolled patients.  This data includes age, 
sex, comorbidities, date of symptom onset, type of admission, APACHE score, 
SOFA score, clinical status, vital signs including temperature, respiratory rate, 
oxygen saturation, oxygen requirement, CBC with neutrophil counts, lymphocyte 
count, complete metabolic panel, liver function tests, CRP, chest x-ray, chest CT, 
location in hospital.   
• Safety and efficacy: Day 0 (baseline), 1, 2, 3, 7, 14, and 28 and once monthly at 
2-3 months.  

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• SARS-CoV-2 PCR from nasopharyngeal swabs: Day 0, 3, 7, 14 to assess 
viremia response.  Other clinically-approved SARS-CoV-2 testing may be used if 
available (e.g. saliva, nares, blood). 
• Biomarker tests performed in the research lab (e.g. antibody titer, cytokine levels) 
on day 0, 1, 3, 7, 14, additional days 21 and 28 may be included, as available.    
• Post-therapy outcomes: increased O2 requirement (PaO2/FiO2 ratio or 
SpO2/FIo2), supplemental oxygen strategy (e.g. nasal cannula, high-flow nasal 
cannula, noninvasive ventilation, intubation and invasive mechanical ventilation, 
rescue ventilation i.e. neuromuscular blocking agents, prone positioning, 
corticosteroids, ECMO), vasopressors, renal support, ICU LOS, ICU mortality, 
Hospital LOS, Hospital mortality, 28 day mortality. 
  
Study Agent:  
• 
SARS-CoV-2 convalescent plasma (1 unit, on average ~300 mLs) 
  
Primary Objective/Outcome:  
1. Feasibility of performing study pathway consisting of consenting convalescent 
donors, harvesting convalescent plasma, application for FDA eIND and 
administering convalescent plasma to the patients 
a. Feasibility will be defined as 6-7 recipient subjects out of a total proposed 
number of 10 recipient subjects will complete the study infusion of plasma 
and be evaluable for follow-up with at least 24 hours’ worth of data post 
transfusion.  Post-transfusion data will include assessment of the study 
process, outcome endpoints and safety endpoints. 
2. Type and duration of respiratory support (e.g. CPAP, BiPAP, high-flow nasal 
cannula, mechanical ventilation)  
  
Primary Endpoint: Number of patients meeting inclusion criteria who received anti-
SARS-CoV-2 convalescent plasma in the study period 
 
Secondary endpoints: 
1. Cardio-circulatory arrest (at any time) 
2. Transfer to ICU 
3. ICU mortality and LOS 
4. Hospital mortality and LOS 
5. Ventilator-free days 
6. 28 day mortality 
  
Primary Safety Objective: Evaluate the safety of an investigational treatment with anti-
SARS-CoV-2 plasma in hospitalized patients with severe or life-threatening COVID-19 
  
Primary Safety Endpoints: 
1. Rapid deterioration of respiratory or clinical status during transfusion of anti-
SARS-CoV-2 convalescent plasma  
2. Cumulative incidence of serious adverse events during the study period: 
transfusion reaction (fever, rash), transfusion related acute lung injury (TRALI), 

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transfusion associated circulatory overload (TACO), transfusion related infection, 
new acute respiratory distress syndrome (ARDS). 
  
Secondary Objectives:   
1. Measure rates, levels and duration of SARS-CoV-2 RNA in nasopharyngeal 
swabs using RT-PCR among recipients.  Other specimen types may be tested as 
available (e.g., BAL fluid, tracheal secretions, sputum, etc.) or when RT-PCR 
assays are validated for additional sources (i.e., stool, blood). 
2. Biomarker tests performed in the research lab (e.g. antibody titers, cytokine 
levels) at days 0, 1, 3, 7 and 14 (additional days 21 and 28 may be included, as 
available) in the recipient. 
 
Study population: 
Plasma Donor Inclusion Criteria for Enrollment 
• Age greater or equal to 18 
• Able to donate blood per blood bank standard guidelines 
• Prior diagnosis of COVID-19 documented by a laboratory test.  Patients outside 
of the UCMC medical system will be asked to provide documentation of COVID-
19 positive test 
• Complete resolution of symptoms at least 28 days prior to donation 
• Female donors who have never been pregnant, previously pregnant female 
donors negative for HLA antibodies (HLA screening), or male donors 
 
Plasma Donor Subject Exclusion Criteria for Enrollment 
• Does not provide consent 
• Does not meet standard blood bank donation guidelines 
• Unsuccessful blood donation 
 
Convalescent plasma donor subjects are consenting for plasma donation 
towards hospitalized patients with severe or life-threatening COVID-19 disease.  
Convalescent plasma units in the UCM Blood Bank collected under this protocol 
will be used for the currently approved Expanded Access Protocol IRB20-0825.  
 
Plasma Recipient Subject Inclusion Criteria for Enrollment 
• Patients must be 18 years of age or older 
• Must have laboratory-confirmed COVID-19 
• Must have severe or immediately life-threatening COVID-19 
o Severe defined as dyspnea, respiratory frequency ≥ 30/min, blood 
oxygen saturation ≤ 93%, partial pressure of arterial oxygen to fraction 
of inspired oxygen ratio < 300, and/or lung infiltrates > 50% within 24 to 
48 hours 
o Life-threatening defined as respiratory failure, septic shock, and/or 
multiple organ dysfunction or failure.  Lower priority should be given to 
patients with septic shock or multiple organ dysfunction or failure since 
their disease may have progressed to a point where they are not able 
to benefit from convalescent plasma therapy. 

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• Must be less than 21 days from the start of illness 
• Patient is willing and able to provide written informed consent and comply 
with all protocol requirements.  If the patient is not able to consent, we will 
obtain consent from the power of attorney or a health care proxy for the 
patient as determined by the Illinois Healthcare Surrogate Act 
• Patient, power of attorney or health care proxy agrees to storage of 
specimens for future testing. 
• Of note, eIND application for each recipient subject will need to be approved 
before administration of convalescent plasma  
 
Plasma Recipient Subject Exclusion Criteria 
• Female subjects with positive pregnancy test, breastfeeding, or planning to 
become pregnant/breastfeed during the study period 
• Receipt of pooled immunoglobulin in past 30 days  
• Contraindication to transfusion or history of prior reactions to transfusion 
blood products 
• Patients currently enrolled in other drug trials that preclude investigational 
treatment with anti-SARS-CoV-2 convalescent plasma 
 
 
 
 
 

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Anticipated study workflow pathway: donor subjects 
 
 
 
 
Appropriate donor subject is recruited, screened and consented
Donor subject is given the intake questionnaire by phone
Donor is screened at the UCM Blood Donation Center for eligiblity for blood donation using 
standard criteria.  If eligible,
- Donor subject donates whole blood 
- In addition to standard donor samples for infectious disease testing and compatibility testing, one 
additional red top tube will be collected for SARS-CoV-2 serologic testing
Donor blood product will be processed according to standard UCM Blood Bank procedures
• Includes HLA screening for female donors
• WB leukoreduction filters which are normally discarded will be given to Patrick Wilson Lab for development of anti-COVID-19 
therapeutics.  These will only be labeled with the donor identification number.
Additional red top tube (labeled with donor identification number) will be given to research 
team for biomarker tests performed in the research lab, e.g. antibody titer
- Plasma stored in freezer -20C, tagged as coming from an eligible convalescent donor
- Once standard donor samples for infectious disease testing and compatibility testing are complete and 
acceptable, blood products are labeled and brought into active inventory
- Plasma will be stored in a separate portion of freezer storage specific for COVID-19 convalescent plasma 
- Plasma transfusion is ordered, using standard UCM EPIC order entry process
- Research team has informed UCM Blood bank of eligible patients who are eligible to 
receive convalescent plasma
ABO-compatible plasma is thawed prior to administration to patient

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Anticipated clinical workflow pathway: recipient subjects 
 
 
 
 
Recipient subject is identified, screened and consented
Application for FDA eIND by study staff MDs or 
treatment team
Recipient subject study samples are obtained 
Recipient subject undergoes plasma transfusion after 
eIND is approved by the FDA
Recipient subject undergoes monitoring and study 
sampling according to study schedule

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List of Abbreviations 
ADR: Adverse Drug Reaction 
ADE: Antibody-mediated enhancement of infection 
AE: Adverse Event/Adverse Experience 
CDC: United States Centers for Disease Control and Prevention 
CFR: Code of Federal Regulations 
CLIA: Clinical Laboratory Improvement Amendment of 1988 
COI: Conflict of Interest 
COVID-19: Coronavirus Disease  
CRF: Case Report Form 
DMC: Data Management Center 
DSMB: Data and Safety Monitoring Board 
EUA: Emergency Use Authorization 
eIND: Emergency Investigational New Drug Application 
FDA: Food and Drug Administration 
GCP: Good Clinical Practice 
HBV: Hepatitis B virus 
HCV: Hepatitis C virus 
HIV: Human immunodeficiency virus 
HLA: Human Leukocyte Antigen 
HTLV: Human T-cell lymphotropic virus 
IB: Investigator’s Brochure 
ICF: Informed Consent (Informed Consent Form) 
ICH: International Conference on Harmonization 
ICU: Intensive Care Unit 
IEC :Independent ethics committee 
IND: Investigational New Drug Application 
IRB: Institutional review board 
ISBT: International Society of Blood Transfusion 
ISM: Independent Safety Monitor 
IWRS :Interactive web response system 
MERS: Middle East Respiratory Syndrome  
NA: Nuclear antibody  
NP: Nasopharyngeal  
OP: Oropharyngeal 
RT-PCR: Reverse Transcriptase Real-Time Polymerase chain reaction 
PBMCs: peripheral blood mononuclear cells 
PK: Pharmacokinetic 
SAE: Serious adverse event 
SARS: Severe Acute Respiratory Syndrome 
SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2 
TACO: Transfusion-associated circulatory overload 
T. cruzi: Trypanosoma cruzi 
TRALI: Transfusion-related acute lung injury 
UCMC: University of Chicago Medical Center 
UP: Unanticipated Problem 

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UPnonAE: Unanticipated Problem that is not an Adverse Event 
ZIKV: Zika virus 
 
 
 

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Background and scientific rationale  
 
Beyond supportive care, there are currently no proven treatment options for coronavirus 
disease (COVID-19), the infection caused by Severe Acute Respiratory Syndrome 
Coronavirus 2 (SARS-CoV-2). Human convalescent plasma is an option for treatment of 
COVID-19 and could be rapidly available when there are sufficient numbers of people 
who have recovered and can donate high titer neutralizing immunoglobulin-containing 
plasma. 
 
Passive antibody therapy involves the administration of antibodies to a given agent to a 
susceptible individual for the purpose of preventing or treating an infectious disease due 
to that agent. In contrast, active vaccination requires the induction of an immune 
response that takes time to develop and varies depending on the vaccine recipient. 
Some immunocompromised patients fail to achieve an adequate immune response. 
Thus, passive antibody administration is the only means of providing immediate 
immunity to susceptible persons and immunity of any measurable kind for highly 
immunocompromised patients. Passive antibody therapy grants immediate passive 
immunity to patients through the transfer of virus-neutralizing antibody derived from 
people who have recovered from infectious disease.   
 
Passive antibody therapy has a storied history going back to the 1890s and was the 
only means of treating certain infectious diseases prior to the development of 
antimicrobial therapy in the 1940s (1,2). This strategy has been successfully used 
during SARS, MERS, influenza 1918, influenza A H1N1, and Ebola outbreaks, with 
demonstrable safety, efficacy and decrease in mortality as detailed below.  Experience 
from prior outbreaks with other coronaviruses, such as SARS-CoV-1 shows that such 
convalescent plasma contains neutralizing antibodies to the relevant virus (3).  In the 
case of SARS-CoV-2, the anticipated mechanism of action by which passive antibody 
therapy would mediate protection is viral neutralization. However, other mechanisms 
may be possible, such as antibody dependent cellular cytotoxicity and/or phagocytosis. 
Convalescent serum was also used in the 2013 African Ebola epidemic.  A small non-
randomized study in Sierra Leone revealed a significant increase in survival for those 
treated with convalescent whole blood relative to those who received standard 
treatment (4).   
 
The only antibody type that is currently available for immediate use is that found in 
human convalescent plasma. As more individuals contract COVID-19 and recover, the 
number of potential donors will continue to increase.  A general principle of passive 
antibody therapy is that it is more effective when used for prophylaxis than for treatment 
of disease.  When used for therapy, antibody is most effective when administered 
shortly after the onset of symptoms. The reason for temporal variation in efficacy is not 
well understood but could reflect that passive antibody works by neutralizing the initial 
inoculum, which is likely to be much smaller than that of established disease. Another 

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explanation is that antibody works by modifying the inflammatory response, which is 
also easier during the initial immune response, which may be asymptomatic (5).  
 
For passive antibody therapy to be effective, a sufficient amount of antibody must be 
administered. When given to a susceptible person, this antibody will circulate in the 
blood, reach tissues and provide protection against infection. Depending on the 
antibody amount and composition, the protection conferred by the transferred 
immunoglobulin can last from weeks to months.  In addition, administration of passive 
antibody therapy does not preclude a patient from receiving future monoclonal antibody 
therapy or vaccines which may be developed for COVID-19. 
 
Experience with the use of convalescent plasma against coronavirus 
diseases  
 
In the 21st century, there were two other epidemics with coronaviruses that were 
associated with high mortality, SARS1 in 2003 and MERS in 2012. In both outbreaks, 
the high mortality and absence of effective therapies led to the use of convalescent 
plasma. The largest study involved the treatment of 80 patients in Hong Kong with 
SARS (7). Patients treated before day 14 had improved prognosis defined by discharge 
from hospital before day 22.  It is also possible that other types of non-neutralizing 
antibodies are made that contribute to protection and recovery as described for other 
viral diseases (11).  
 
Among reports of seriously ill individuals treated with convalescent plasma, three 
patients with SARS in Taiwan were treated with 500 ml of convalescent plasma, 
resulting in a reduction in plasma virus titer and each survived (8). Three patients with 
MERS in South Korea were treated with convalescent plasma, but only two of the 
recipients had neutralizing antibody in their plasma (9).  The latter study highlights a 
challenge in using convalescent plasma, namely, that some who recover from viral 
disease may not have high titers of neutralizing antibody (10).  Strikingly, a recent 
report from China where 10 patients with severe COVID-19 received human 
convalescent plasma (SARS-CoV-2 convalescent plasma) on day 10 to 20 of 
illness demonstrated improvement in clinical, radiographic and laboratory 
parameters such that patients were discharged to home and suffered no severe 
adverse effects 
(https://www.medrxiv.org/content/10.1101/2020.03.16.20036145v1.full.pdf).  These 
patients received plasma from donor blood collected from hospitalized patients three 
weeks after illness start and 4 days after discharge.  The donors had to demonstrate 
criteria of recovery which were (a) normal temperature for at least 3 days; (b) resolution 
of respiratory tract symptoms; (c) 2 consecutively negative RT-PCR sputum results with 
one-day sampling interval.   This was followed by a report by a separate group in China 
in JAMA on March 27, 2020 showing that 5 critically ill patients, including one on extra-
corporeal membrane oxygenation (ECMO) support, who received low titer antibody 
serum with high virus neutralizing activity, were able to recover (Shen C, Wang Z, Zhao 
F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. 

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JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783.  Although few 
details are available from the Chinese experience and published studies involved small 
numbers of patients, the available information suggests that convalescent plasma 
administration reduces viral load and is safe. 
 
In these rapidly changing times, several groups across the United States have 
highlighted the importance of convalescent plasma in the anti-COVID-19 arsenal.  
These groups include National Academies of Sciences, Engineering, and Medicine 
(https://www.nationalacademies.org/news/2020/statement-from-the-presidents-of-the-
nas-nae-and-nam-supporting-steps-necessary-to-assess-the-potential-for-human-
convalescent-plasma-to-help-control-covid-19) and the AABB American Association of 
Blood Banking 
(http://www.aabb.org/advocacy/regulatorygovernment/Documents/COVID-19-
Convalescent-Plasma-Resources.pdf).   
 
In addition, the AABB with FDA support is currently working to establish a “master 
collection protocol under which blood centers would be able to quickly implement 
uniform practices to expedite the availability” of convalescent plasma.  Because there 
are no currently available treatments for COVID-19, the FDA has approved the 
emergency investigational use of convalescent plasma to treat COVID-19 under the 
criteria of the single patient emergency investigational new drug application (eIND) 
(https://www.fda.gov/media/136470/download) (https://www.fda.gov/vaccines-blood-
biologics/investigational-new-drug-ind-or-device-exemption-ide-process-
cber/investigational-covid-19-convalescent-plasma-emergency-inds). 
 
Known potential risks 
The theoretical risk involves the phenomenon of antibody-mediated enhancement of 
infection (ADE). ADE can occur for several viral diseases and involves an enhancement 
of disease in the presence of certain antibodies. For coronaviruses, several 
mechanisms for ADE have been described and there is the theoretical concern that 
antibodies to one type of coronavirus could enhance infection to another viral strain 
(12). It may be possible to predict the risk of ADE of SARS-CoV-2 experimentally, as 
proposed for MERS. Since the proposed use of convalescent plasma in the COVID-19 
pandemic would rely on preparations with high titers of neutralizing antibody against the 
same virus, SARS2-CoV-2, ADE may be unlikely. The available evidence from the use 
of convalescent plasma in patients with SARS1 and MERS (13) and anecdotal evidence 
of its use in patients with COVID-19 (http://www.xinhuanet.com/english/2020-
02/28/c_138828177.htm, 
https://www.medrxiv.org/content/10.1101/2020.03.16.20036145v1.full.pdf), suggest it is 
safe. However, because of these potential risks, we are limiting administration of SARS-
CoV-2 convalescent plasma to patients with severe or life-threatening COVID-19 at this 
time.  Caution and vigilance will be required for any evidence of enhanced infection. 
 
Another theoretical risk is that antibody administration to those exposed to SARS-CoV-2 
may avoid disease but modify the immune response such that those individuals mount 

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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 immunity 
(14).   If the concern proved real, these individuals could be vaccinated against COVID-
19 when a vaccine becomes available.  Furthermore, this issue will be investigated by 
measuring immune responses in those exposed and treated with convalescent plasma 
to prevent disease in an ongoing clinical trial.  In addition, once serum antibody testing 
becomes readily available, immunity can be more reliably assessed, These concerns 
seem modest compared to the possibility of limiting the duration and severity of disease, 
and avoiding interventions like mechanical ventilation, ARDS and sepsis. 
 
Finally, there are risks associated with any transfusion of plasma including transmission 
of transfusion transmitted viruses (e.g. HIV, HBV, HCV, etc.), allergic transfusion 
reactions, anaphylaxis to transfusion, febrile transfusion reaction, transfusion related 
acute lung injury (TRALI), and transfusion associated cardiac overload (TACO).  
Infectious risks are minimized by collecting only eligible donors and testing donors for all 
FDA-required infectious diseases as part of standard allogeneic donor blood collection.  
TRALI is mitigated by collecting male donors, female donors who have never been 
pregnant, or previously pregnant women who are negative for HLA antibodies.  Donors 
will fulfill all donor requirements for whole blood donation.  The standard volume of 
plasma (~300 mL) will be transfused over a longer time period (4 hours) and the patient 
will be monitored for signs of overload.  
 
Known potential benefits 
 
A key potential benefit is the potential treatment for established infection.  Convalescent 
plasma would be administered to those with clinical disease in an effort to reduce their 
symptoms and mortality. Based on the recent evidence from China with antibody 
administration, it can be anticipated that antibody administration in patients with severe 
COVID-19 could improve mortality, decrease ICU needs and reverse ventilator- or 
oxygen-dependence in carefully selected patients.  
 
Given that historical and current anecdotal data on use of convalescent plasma suggest 
it is safe in coronavirus infection, the high mortality of COVID-19, particularly in elderly 
and vulnerable persons, suggests that the benefits of its use in those at high risk for 
disease outweigh the risks. However, for all cases where convalescent plasma 
administration is considered, a risk-benefit assessment must be conducted to assess 
individual variables. 
 
Investigational plan 
 
Study Objectives 
 
Primary Objective:  

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1. Feasibility of performing clinical pathway for convalescent plasma therapy 
consisting of consenting convalescent donors, harvesting anti-SARS-CoV-
2 convalescent plasma, application for single patient eIND to the FDA and 
administering anti-SARS-CoV-2 convalescent plasma to the patients 
meeting study criteria 
 
2. Type and duration of respiratory support (e.g. CPAP, BiPAP, high-flow 
nasal cannula, mechanical ventilation)  
 
 
Primary Safety Objective:  
Evaluate the safety of investigational treatment with anti-SARS-CoV-2 plasma 
in hospitalized patients with severe or life-threatening COVID-19 
 
Secondary Objectives: 
Biomarker tests performed in the research lab (e.g. antibody titer, cytokine 
levels) at days 0, 1, 3, 7 and 14 (additional days 21 and 28 may be included, 
as available) in the recipient.   
 
Measure rates, levels and duration of SARS-CoV-2 RNA in nasopharyngeal 
swabs using RT-PCR among recipients.  Other specimen types may be tested 
as available (eg., BAL fluid, tracheal secretions, sputum, etc.) or when RT-
PCR assays are validated for additional sources (i.e., stool, blood). 
 
Definitions  
 
• Enrolled: From time consented to participate until designated as a screen failure or 
have either been discontinued from the study or completed it.  
• Screen Failures: signed informed consent, but then determined to be ineligible or 
withdraws  
• Discontinued: withdrawn by investigator or withdraws consent 
• Completed: Subjects are considered to have completed when they are followed 
through day 90 or have had an adverse event or death occurred prior to day 90.   
 
Study population 
 
Plasma Donor Subject Inclusion Criteria for Enrollment 
• Age 18 or older 
• Able to donate blood per blood bank standard guidelines 
• Prior diagnosis of COVID-19 documented by a laboratory test.  Patients outside 
of the UCMC medical system will be asked to provide documentation of COVID-
19 positive test. 
• Complete resolution of symptoms at least 28 days prior to donation 
• Female donors who have never been pregnant, previously pregnant female 
donors negative for HLA antibodies (HLA screening), or male donors 

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Plasma Donor Subject Exclusion Criteria for Enrollment 
 
• 
Unable to give consent 
• 
Unable to donate blood per blood bank standard guidelines 
• 
Unsuccessful blood donation 
 
Plasma Recipient Subject Inclusion Criteria for Enrollment 
 
• Patients must be 18 years of age or older 
• Must have laboratory-confirmed COVID-19 
• Must have severe or immediately life-threatening COVID-19 
o Severe defined as dyspnea, respiratory frequency ≥ 30/min, blood oxygen 
saturation ≤ 93%, partial pressure of arterial oxygen to fraction of inspired 
oxygen ratio < 300, and/or lung infiltrates > 50% within 24 to 48 hours 
o Life-threatening defined as respiratory failure, septic shock, and/or 
multiple organ dysfunction or failure. Lower priority should be given to 
patients with septic shock or multiple organ dysfunction or failure since 
their disease may have progressed to a point where they are not able to 
benefit from convalescent plasma therapy. 
• Must be less than 21 days from the start of illness 
• Patient is willing and able to provide written informed consent and comply with all 
protocol requirements.  If the patient is not able to consent, we will obtain 
consent from the power of attorney or a health care proxy for the patient as 
determined by the Illinois Healthcare Surrogate Act 
• Patient, health care proxy or power of attorney agrees to storage of specimens 
for future testing. 
• eIND application for each recipient subject will need to be approved before 
administration of convalescent plasma 
 
Plasma Recipient Subject Exclusion Criteria 
 
• Female subjects with positive pregnancy test, breastfeeding, or planning to 
become pregnant/breastfeed during the study period 
• Receipt of pooled immunoglobulin in past 30 days  
• Contraindication to transfusion or history of prior reactions to transfusion blood 
products 
• Patients currently enrolled in other drug trials that preclude treatment with anti-
SARS-CoV-2 convalescent plasma.   
 
 
 

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Recruitment (Plasma Donors) 
 
Plasma donor subjects in the groups listed below will be  contacted to obtain electronic consent 
to donate blood.   
Patients who are on the list of COVID-19 positive patients maintained by the infectious disease 
team at the University of Chicago Medical Center (UCMC) The primary care physician or 
attending of patients who are on the list of COVID-19 positive patients maintained by the 
infectious disease team at the University of Chicago Medical Center.  
1. People who are undergoing COVID-19 testing at UCMC will be asked about donating 
blood. .      
2. Advertisement of this study will take place in community bulletins, throughout the 
university with posters/fliers, on the internet, UCMC press release and in the local news.   
 
We have a dedicated call center number and email address to field questions from people who 
are interested in the study or who may be potential plasma donors to reach us.   
 
A secure email address at the University of Chicago has been made. .  Emails to this address 
will generate an automatic reply (detailed in the attached recruitment materials).  Emails will be 
viewed by the study staff who will be able to respond if potential participants want to learn more 
about this research study. 
 
 
 

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Schedule of Events 
 
Schedule of Events for Plasma Donor Subjects 
 
Table 1. Schedule of events for plasma donor subjects:  
 
Study period 
Screen 
Enroll 
 
Donation 
Day 
-90 to -28 
days 
-1 days or 
more 
 
0 
Test positive for COVID-19 
Patients outside of the UCMC medical 
system will be asked to provide 
documentation of COVID-19 positive test 
x 
 
 
 
Subject recruitment and screening 
 
x 
 
 
Consent for participation in donor portion 
of study  
 
X 
 
 
Donor intake questionnaire via redcap. 
 
X 
 
 
Consent for blood donation using 
standard UCM Blood Donation 
processes and procedure 
 
 
 
x 
Donation at UCMC Blood Bank 
 
 
 
x 
 
 
 
 

Version 20May2020 
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Table 2: Schedule of Events for Plasma Recipient Subject 
Study period 
Screen 
Baseline 
Transfusion 
Follow-up 
Day 
-7 to 0 
0 
0 
1 
3 
7 
14 
281 
Eligibility 
Informed consent 
x 
 
 
 
 
 
 
 
Demographic and Medical history 
x 
 
 
 
 
 
 
 
COVID-19 symptom screen 
x 
 
 
 
 
 
 
 
Pregnancy test 
x 
 
 
 
 
 
 
 
ABO 
x 
 
 
 
 
 
 
 
Application for single patient eIND 
FDA compassionate use for 
convalescent plasma 
x 
 
 
 
 
 
 
 
eIND is approved 
x 
 
 
 
 
 
 
 
Study Plasma Administration 
Plasma infusion 
 
 
X 
 
 
 
 
 
Study Procedures 
 
 
 
 
 
 
 
 
Vital signs 
x 
x 
xxxx2 
x 
x 
x 
x 
 
Physical examination  
x 
 
x 
x 
 
x 
 
 
Symptom screen 
x 
x 
x 
x 
x 
x 
x 
x 
Concomitant medications 
x 
x 
x 
 
 
 
 
 
Assessment with 7-point ordinal scale 
 
x 
 
x 
x 
x 
x 
x 
Adverse event monitoring 
 
x 
x 
x 
x 
x 
x 
x 
Laboratory testing  
CBC and CMP 
 
x 
 
x 
x 
x 
x 
 
Chest x-ray or CT chest if available 
x 
 
 
x 
x 
x 
x 
 
SARS-CoV-2 RT-PCR 
 
x 
 
 
x 
x 
x 
 
Blood samples for biomarker tests 
performed in the research lab 
 
x 
 
x 
x 
x 
x 
 
 
Biomarker tests performed in the research lab include antibody titer, neutralizing antibody, cytokine 
levels, viremia  
 
                                                 
1 The assessments performed on day 28 will be repeated on days 60 and 90. 
2 Vital sign testing: Immediately prior to infusion, 10-20 minutes after start of infusion, at 
completion of infusion and 30-60 minutes after the end of the infusion 

Version 20May2020 
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Subject Withdrawal 
 
• Subjects can terminate study participation and/or withdraw consent at any time 
without prejudice.  
• Subjects who withdraw from the study will not be replaced. 
• The investigator may withdraw subjects if they are lost to follow up, non-
compliant with study procedures or if the investigator determines that continued 
participation in the study would be harmful to the subject or the integrity of the 
study data. 
• Discontinuation of the study: The IRB has the right to terminate this study at any 
time 
Investigational plasmaTreatment  
 
• Recipient subjects will receive anti-SARS-CoV-2 convalescent plasma as a pilot 
study after approval of single patient eIND application. 
• Recipient subjects will receive anti-SARS-CoV-2 convalescent plasma under 
IRB20-0825 
• Investigational Product: The investigational product is anti-SARS-CoV-2 
convalescent plasma obtained from donors identified as having recovered from 
COVID-19.  
• 
Donors samples will have been screened for transfusion-transmitted infections 
(e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T.cruzi, syphilis, ZIKV) both through the 
use of the UCM Blood Donation Center Blood Donation Record and FDA-
mandated blood donor screening tests.   Plasma will have been collected as 
whole blood derived units donations and in accordance with standard FDA and 
blood bank protocols.  Plasma will be ABO-compatible and HLA-screened per 
standard FDA and blood bank protocols. 
• Recipient subjects will receive 1 unit of convalescent plasma after eIND approval.  
When CLIA clinical testing for antibody is available, plasma will be transfused 
with an anti-SARS-CoV-2 titer of >1:320, though this titer may be adjusted as in 
vitro titer assays of virus neutralization are correlated with in vivo assessments of 
virus neutralization.   
• Plasma will be labeled according to FDA and blood bank guidelines. 
Research biomarkers and other studies 
 
During standard whole blood donation, peripheral blood mononuclear cells (PBMCs) are 
collected by the leukoreduction filter.  This filter is normally discarded.  Instead of 
discarding this filter as per usual practice, the filter will be labeled with the donor 
identification number and will be given to Patrick Wilson’s laboratory for the isolation of 
B cells reactive to recombinant proteins from SARS-CoV-2 for the synthesis of 
monoclonal antibodies. These antibody proteins will be characterized for binding to 
COVID-19 proteins and other protective activities against the virus. These antibodies 
will be valuable as possible therapeutic agents or for the production of high-sensitivity 

Version 20May2020 
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and high-specificity diagnostic reagents. These antibodies will also guide and template 
the generation of vaccines to protect against COVID-19. A small aliquot of serum from 
the patient blood samples will also be analyzed for binding to the various COVID-19 
proteins we have access to by ELISA to learn which COVID-19 proteins are the most 
immunogenic, further guiding vaccine design efforts.    
 
Per FDA guidelines, convalescent serum containing neutralizing antibody with a titer 
optimally greater than 1:320 should be used when antibody titer tests are available.  
Antibody testing is currently only available in research labs (Patrick Wilson at the 
University of Chicago).  When antibody testing is available in clinical labs, we will be 
able to use titer information to guide plasma transfusion, e.g. titer can be adjusted as in 
vitro titer assays of virus neutralization are correlated with in vivo assessments of virus 
neutralization.  This will identify individuals who have anti-SARS-CoV-2 neutralizing 
antibody and identify the strength of the virus-neutralizing antibody in each titer 
concentration.   
 
 
Rationale for doses  
 
The dose of 1 unit; ~300 mL was chosen to minimize volume given to a patient with 
compromised pulmonary function/acute respiratory distress syndrome, which fits the 
profile of COVID-19 patients with severe disease.   
 
Investigational treatment-plasma administration 
 
• Plasma will be administered after enrollment and approval of single patient 
eIND by the FDA or under the expanded access protocol IRB20-0825 
• Infusion rate will be ~300 mL over 4 hours (~50 mL per hour) 
• Pretreatment to minimize transfusion reactions (e.g. acetaminophen, 
diphenhydramine) may be given per investigator and clinical care team 
discretion.  
• If an AE develops during infusion, the infusion may be slowed or stopped as 
per investigator’s decision.  
o Most reactions to plasma are relatively minor and the infusion can 
generally be continued. Infusion site burning and non-allergic systemic 
effects can generally be managed with slowing of the infusion. Infusion 
can generally be continued in cases of itching or hives after pausing 
the transfusion, administering antihistamines, and observing the 
patient for worsening.   
o Severe allergic reactions such as, bronchospasm and hypotension, 
and may require discontinuation of the infusion.  
 
Concomitant medications will be documented on the CRF 
• Prescription medications 
• Over the counter medications 

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• Herbal treatments/nutritional supplements 
• Blood products 
 
Statistical considerations 
 
 
Statistical Analysis  
 
This is a pilot study focused on determining the protocol feasibility with limited 
subject enrollment. Therefore, statistical analysis will include descriptive 
summaries of both the primary and secondary outcomes of interest. For 
continuous variables we will determine: median, minimum and maximum values. 
Categorical variables will be summarized by the frequency. Unless otherwise 
indicated, percentages in tables will be column percentages, using the total 
number of observations in the population (n=10), as the denominator. 
Percentages will be rounded to one decimal place, and thus may not always add 
up to exactly 100%. Clinical laboratory values will be first reported in using 
International System of Units (SI).  
 
 
 
 

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Analysis of AE data 
 
Analysis of AE data will primarily be descriptive based on MedDRA coding of 
events. The proportion of subjects experiencing an SAE and the proportion 
experiencing a Grade 3 or higher AE will be measured. 
 
Analysis of SARS-CoV-2 viremia 
 
Analysis of SARS-CoV-2 viremia will primarily be descriptive, comparing the 
viremia levels at days 0,1,3,7 and 14 between the subject recipients.  
 
Analysis of research biomarkers  
 
Analysis of biomarker tests performed in the research lab such as antibody titers, 
cytokine levels will primarily be descriptive, comparing the titers at days 0,1,3,7 
and 14 between subject recipients.  
 
Endpoints  
 
Primary Endpoint:  
1. Feasibility of performing study pathway consisting of consenting convalescent 
donors, harvesting convalescent plasma, application for FDA eIND and 
administering convalescent plasma to the patients 
2. Type and duration of respiratory support (e.g. CPAP, BiPAP, high-flow nasal 
cannula, mechanical ventilation)  
 
Secondary endpoints: 
1. Cardio-circulatory arrest (at any time) 
2. Transfer to ICU 
3. ICU mortality and LOS 
4. Hospital mortality and LOS 
5. Ventilator-free days 
6. 60 day mortality 
 
Primary Safety Endpoints:  
1. Rapid deterioration of respiratory or clinical status on transfusion of anti-
SARS-CoV-2 convalescent plasma  
2. Cumulative incidence of serious adverse events during the study 
period: transfusion reaction (fever, rash), transfusion related acute lung 
injury (TRALI), transfusion associated circulatory overload (TACO), 
transfusion related infection 
 
Secondary Endpoints 

Version 20May2020 
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1. Rates and duration of SARS-CoV-2 PCR positivity (RT-PCR) at days 0, 
3, 7, and 14.  
 
 
Study procedures for plasma donors 
 
Study procedures for plasma donors who enter the study through the 
following mechanisms: 
• 
Patients who are on the list of COVID-19 positive patients maintained by the 
infectious disease team at the University of Chicago Medical Center (UCMC)  
• 
The primary care physician or a treatment team attending of patients who are 
on the list of COVID-19 positive patients maintained by the infectious disease 
team at the University of Chicago Medical Center.   
• 
People who are undergoing COVID-19 testing at UCMC.      
• 
Advertisement of this study will take place in community bulletins, throughout 
the university with posters/fliers, on the internet, UCMC press release and in 
the local news to ask whether anyone would like to donate blood and 
participate in this research study.   
 
Day -28 to -90:  
• 
Tested positive for COVID-19.  People outside of the UCMC medical 
system will be asked to provide documentation of COVID-19 positive test. 
 
Day -28 to -90:  
• 
Complete resolution of all COVID-19 symptoms 
 
Day -1 or more:  
• 
Screening for plasma donor inclusion criteria 
• 
Consent for participation in donor portion of study 
• 
Donor questionnaire 
 
Day 0:  
• 
Consent for blood donation using standard UCM Blood Donation 
processes and procedure 
• 
Blood donation at the UCM Blood Donation Center 
 
 
 
Study procedures for investigational plasma recipient 
 
Day -7 to 0:  
1. Screening for patient inclusion criteria 
2. Subject informed consent (obtained before performing study related activities).  

Version 20May2020 
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3. Baseline Evaluation (at screening) (much of the information will be obtained from 
the medical record) 
• Demographics (Age, sex ethnicity, race) 
• Medical history (timing of exposure to COVID-19 source patient, acute and 
chronic medical condition, medications, allergies, any drug trial therapy. Any 
medical condition arising after consent should be recorded as AE 
• COVID-19 symptom screen (fevers, cough, shortness of breath), day of onset 
of symptoms 
• Vital signs 
• COVID-19 testing (RT-PCR) from nasopharyngeal, throat, blood or stool 
(optional) samples.  Other clinically-approved SARS-CoV-2 testing may be 
used if available (e.g. saliva, nares, blood). 
• Blood typing, CBC, comprehensive metabolic panel 
• Urine or serum pregnancy test for females of childbearing potential. Results 
from laboratory tests obtained up to 7 days before enrollment may be used for 
the pregnancy test. 
• Stored samples for biomarker tests performed in the research lab (e.g. 
antibody titer, cytokines)  
• Determination of eligibility as per inclusion/exclusion criteria 
4. Application and approval of eIND per FDA guidelines for single patient 
compassionate use of convalescent plasma 
 
DAY 0:  
1. Study Plasma Administration:  1 unit of plasma will be transfused. Time at 
start and end of infusion will be recorded and Vital signs will be measured 
immediately prior to infusion, 10-20 minutes after start of infusion, at 
completion of infusion and 30-60 minutes after the end of the infusion 
2. COVID-19 symptom screen (fevers, cough, shortness of breath) 
3. Assessment of clinical status (7-point ordinal scale) 
4. New medical conditions, concomitant medication, AE evaluation 
5. physical examination 
6. Blood typing, CBC, comprehensive metabolic panel, C-reactive protein 
7. Stored samples for biomarker tests performed in the research lab (e.g. 
antibody titer, cytokines)  
 
Day 1-7 (or for duration of hospitalization) 
1. Vital signs daily 
2. COVID-19 symptom screen (fevers, cough, shortness of breath) 
3. Assessment of clinical status (7-point ordinal scale) 
4. New medical conditions, AE evaluation 
5. physical examination 
6. CBC, comprehensive metabolic panel, CRP daily 
7. COVID-19 testing (RT-PCR) from nasopharyngeal, throat, blood or stool 
(optional) samples.  Other clinically-approved SARS-CoV-2 testing may be 
used if available (e.g. saliva, nares, blood) 

Version 20May2020 
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8. Stored samples for biomarker tests performed in the research lab (e.g. 
antibody titer, cytokines)  
 
Day 28:  
Key issues to consider follow up by phone, alive, at home, in hospital (ICU or 
not), on supplemental O2 or not, back to work, fully, partially, SNF, nursing 
home, LTAC 
 
a. COVID-19 symptom screen (fevers, cough, shortness of breath) 
b. Assessment of clinical status (7-point ordinal scale) 
c. New medical conditions, AE evaluation 
 
Day 60 and 90: 
 
1. COVID-19 symptom screen (fevers, cough, shortness of breath) 
2. Assessment of clinical status (7-point ordinal scale) 
3. New medical conditions, AE evaluation 
 
Efficacy and virology measures 
 
Clinical Efficacy (ordinal scale) 
 
1. Death/Cardio-circulatory arrest at anytime 
2. Transfer to ICU  
3. Type and duration of respiratory support (and other ICU support)  
4. ICU mortality and LOS 
5. Hospital mortality and LOS 
6. Ventilator-free days 
7. 28 day mortality  
 
 
Virologic measures  
 
1. Rates, levels and duration of SARS-CoV-2 RNA in NP swabs by RT-PCR at 
days 0, 3, 7 and 14. Other specimen types may be tested as available (eg., 
BAL fluid, tracheal secretions, sputum, etc.) or when RT-PCR assays are 
validated for additional sources (i.e., stool, blood). 
 
Risks and benefits 
 
Potential Benefits of treatment: 
The potential benefits of antiviral treatment with anti-SARS CoV-2 plasma in 
patients with severe or life-threatening COVID-19 disease are not known.  
However, it is anticipated that treatment will decrease disease progression, 

Version 20May2020 
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decrease ICU or higher-level medical support and possibly reverse disease 
course. 
 
Potential benefits of clinical monitoring and virologic testing: 
Subjects enrolled in the study may reduce their chances of disease progression.    
 
Potential risks: 
1. Risks of plasma: Fever, chills, rash, headache, serious allergic reactions, TRALI, 
TACO, transmission of infectious agents 
2. Risks of phlebotomy: local discomfort, bruising, hematoma, bleeding, fainting, 
3. Total blood draws will not exceed 500 mL 
4. Risks of oropharyngeal and throat swab: local discomfort, vomiting 
 
Alternatives: 
The alternative to participation in this study is supportive care. There are several 
ongoing clinical trials at UCM for COVID-19 patients, such as anti-IL6 therapy, anti-viral 
therapy and hydrochloroquine therapy.   
 
Safety measures 
 
Monitoring procedures 
The PI and co-investigators ensure that informed consent is obtained prior to performing 
any research procedures, that all subjects meet eligibility criteria, and that the study is 
conducted according to the IRB-approved research plan.  
 
Study data are accessible at all times for the team to review, and to the Independent 
Safety Monitor upon request. The PIs and co-investigators review study conduct, 
particularly accrual, drop-outs, and protocol deviations on a quarterly basis. The team 
reviews adverse events (AEs) individually in real-time and in aggregate on a quarterly 
basis. The PIs review serious adverse events (SAEs) in real-time. The PIs ensure that 
all protocol deviations, AEs and SAEs are reported to the IRB according to the 
applicable regulatory requirements. 
 
 
1. Safety Evaluations will assess for the safety of anti-SARS-CoV-2 plasma  
2. Clinical evaluations: Vital signs and symptom screen on days 0-7, 14 and 
symptom screens on days 28, 60, and 90. 
3. Laboratory evaluations consistent with ongoing medical care may include 
radiographic imaging modalities such as chest x-rays and chest CT. 
4. Safety laboratory tests (ABO typing, pregnancy testing, CBC, CRP, and 
comprehensive metabolic panel) will be performed at the local CLIA-certified 
clinical laboratory on days 0-7 and 14. 
 
Event (AE)  
 

Version 20May2020 
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Any untoward medical occurrence in a clinical investigation subject who has 
received a study intervention and that does not necessarily have to have a 
causal relationship with the study product. An AE can, therefore, be any 
unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of the study 
product, whether or not considered related to the study product. 
 
Serious Adverse Event (SAE) 
 
An SAE is any adverse event that results in any of the following outcomes: 
1. Death 
2. Life-threatening (immediate risk of death) 
3. Prolongation of existing hospitalization 
4. Persistent or significant disability or incapacity 
5. Important medical events that may not result in death, be life threatening, or 
require intervention or escalation of care may be considered a serious adverse 
event when, based upon appropriate medical judgment, they may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization. 
 
Unexpected Adverse event: (UAE) An adverse reaction, the nature or severity of which 
is not consistent with the investigator’s brochure. 
  
Unanticipated Problem (UP) 
 
Unanticipated problems involving risks to subjects or others refer to a problem, event or 
information item that is not expected, given the nature of the research procedures and 
the subject population being studied; and which suggests that the research places 
subjects or others at a greater risk of harm or discomfort related to the research than 
was previously known. The IRB considers unanticipated problems, in general, to include 
any incident, experience, or outcome that meets ALL of the following criteria: 
 
1. unexpected (in terms of nature, severity, or frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as the IRB-
approved research protocol, investigator’s brochure, drug or device product information, 
informed consent document, or other research materials; and (b) the characteristics of 
the subject population being studied, including underlying diseases, behaviors, or traits; 
 
2. related or possibly related to participation in the research (possibly related means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research);and 
 

Version 20May2020 
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3. suggests that the research places subjects or others at a risk of unknown harm or 
addition/increased frequency of harms (including physical, psychological, economic, 
legal, or social harm) than was previously known or recognized. 
 
Unanticipated problems may be adverse events, protocol deviations, noncompliance or 
other types of problems, but MUST meet all of the criteria listed above. It is the 
expectation of the IRB that all approved protocol procedures are being followed without 
alteration unless the IRB has been informed of a protocol change or deviation. 
 
Protocol Deviation: Deviation from the IRB-approved study procedures. Designated 
serious and non-serious 
1. Serious Protocol Deviation: Protocol deviation that is also an SAE and/or 
compromises the safety, welfare or rights of subjects or others 
2. Safety Reporting Requirements 
 
Reporting Interval 
All AEs and SAEs will be documented from the first administration of study product until 
completion or un-enrollment from the study. All AEs and SAEs will be followed until 
resolution even if this extends beyond the study-reporting period. Resolution of an 
adverse event is defined as the return to pre-treatment status or stabilization of the 
condition with the expectation that it will remain chronic.  
At any time after completion of the study, if the investigator becomes aware of a SAE 
that is suspected to be related to study product, this will be reported.  
 
Collection and reporting of SAEs and AEs. Documentation of adverse events will be 
determined by the clinician and recorded on the Clinical Adverse Event Report form and 
will include the following infor-mation: Description of the condition, dates of condition, 
treatment of condition (medications, doses, dates), whether emergency treatment was 
required, treatment outcome, relationship of the adverse event to the study 
medication(s) and severity of the event. Additional information about the AE will be 
provided as needed so as to understand the scope of the event.  
 
Management of SAEs. Serious adverse events are always managed, first and foremost, 
based on medical appropriateness so as to ensure subject safety. The PIs are notified 
as soon as pos-sible about an SAE and will work with the medical team to ensure the 
best resolution possible of the problem. In medical emergencies the PIs are permitted to 
provide all health-care providers with appropriate medical information at hand about the 
subject consistent with HIPAA regulations. 
 
Serious adverse events will be forwarded by the PI to the Independent Safety Monitor 
and IRB immediately. Fatal or life-threatening unexpected SAEs will be reported to the 

Version 20May2020 
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IRB immediately.  Non-fatal, non-life-threatening unexpected SAEs will be reported to 
the Independent Safety Monitor within 72 hours. 
 
Investigator’s Assessment of Adverse Events  
 
The determination of seriousness, severity, and causality will be made by an on-site 
investigator who is qualified (licensed) to diagnose adverse event information, provide a 
medical evaluation of adverse events, and classify adverse events based upon medical 
judgment. This includes but is not limited to physicians, physician assistants, and nurse 
practitioners. 
 
Laboratory abnormalities will be reported as AEs if there is a 2 s.d. increase above 
baseline. 
 
 
Assessment of Seriousness 
1. Event seriousness will be determined according to the protocol definition of an 
SAE  
2. Assessment of Severity 
 
Event severity will be assigned according to the scale below 
1 = Mild: Transient or mild discomfort (<48 hours); no medical 
intervention/therapy required.) 
2 = Moderate: Some worsening of symptoms but no or minimal medical 
intervention/therapy required) 
3 = Severe: Escalation of medical intervention/therapy required 
4 = Life-threatening:  Marked escalation of medical intervention/therapy 
required.  
5= Death 
Assessment of Association 
The association assessment categories that will be used for this study are: 
• Associated – The event is temporally related to the administration of the study 
product and no other etiology explains the event. 
• Not Associated – The event is temporally independent of the study product 
and/or the event appears to be explained by another etiology.  

Version 20May2020 
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The investigator must provide an assessment of association or relationship of AEs to 
the study product based on: 
• Temporal relationship of the event to the administration of study product; 
• Whether an alternative etiology has been identified; 
• Biological plausibility; 
• Existing therapy and/or concomitant medications. 
 
Safety Oversight 
Monitoring Plan  
1. All AE and SAW will be reviewed by protocol team in real time.  
2. An Independent Safety Monitor (ISM) has be appointed. The ISM is Dr. O’Connor 
has in infectious diseases and whose primary responsibility is to provide timely 
independent safety monitoring.  An ISM is in close proximity to the study site and 
has the authority to readily access study participant records.  The ISM reviews 
any SAE that occurs at the study site in real time and provides a written 
assessment.  
Study monitoring  
1. As per ICH-GCP 5.18 and FDA 21 CFR 312.50, clinical protocols are required to 
be adequately monitored by Dr. Madariaga, the research team and the Office of 
Clinical research (OCR). Monitors will verify that 
a. There is documentation of the informed consent process and signed 
informed consent documents for each subject 
b. There is compliance with recording requirements for data points 
c. All SAEs are reported as required 
d. Individual subjects’ study records and source documents align 
e. Investigators are in compliance with the protocol. 
f. Regulatory requirements as per Office for Human Research Protections-
OHRP), FDA, and applicable guidelines (ICH-GCP) are being followed.  
 
Halting Criteria for the Study 

Version 20May2020 
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In the event that any of the 6 events listed under “Halting Criteria for the Study” occur, 
the IRB will be immediately notified and the study placed on hold until such time as the 
IRB agreed that study activities could resume.  
The study enrollment and dosing will be stopped and an ad hoc review will be performed 
if any of the specific following events occur or, if in the judgment of the study physician, 
subject safety is at risk of being compromised: 
1. Death within one hour of plasma infusion 
2. Occurrence of a life-threatening allergic/hypersensitivity reaction (anaphylaxis), 
manifested by bronchospasm with or without urticaria or angioedema requiring 
hemodynamic support with pressor medications or mechanical ventilation. , 
TRALI, TACO 
3.  One subject with an SAE associated with study product. 
4. Two subjects with a Grade 3 or higher lab toxicity for the same parameter 
associated with study product. 
5. An overall pattern of symptomatic, clinical, or laboratory events that the medical 
monitor, ISM, or SMC consider associated with study product and that may 
appear minor in terms of individual events but that collectively may represent a 
serious potential concern for safety. 
6. Any other event(s) which is considered to be a serious adverse event in the good 
clinical judgment of the responsible physician.  This will be appropriately 
documented. 
Upon completion of this review and receipt of the advice of the ISM, the IRB will 
determine if study entry or study dosing should be interrupted or if study entry and study 
dosing may continue according to the protocol. 
Halting Criteria/Rules for Subject Infusion 
Infusion of study drug will be halted if any of the following manifestations of anaphylaxis 
develop and will not be restarted: 
• Skin or mucous membrane manifestations: hives, pruritus, flushing, swollen lips, 
tongue or uvula 
• Respiratory compromise: dyspnea, wheezing, stridor, hypoxemia 
• A decrease in systolic blood pressure to < 90 mmHg or >30% decrease from 
baseline or a diastolic drop of >30% from baseline. 

Version 20May2020 
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• Tachycardia with an increase in resting heart rate to > 130bpm; or bradycardia <40 
that is associated with dizziness, nausea or feeling faint. 
• Any other symptom or sign which in the good clinical judgment of the study clinician 
or supervising physician warrants halting the infusion.  For example, the rapid onset 
of  gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and cramps, for 
instance, may be manifestations of anaphylaxis and may warrant an immediate halt 
prior to meeting full SAE criteria 
 
Ethics/Protection of human subjects 
 
Ethical Standard 
The University of Chicago is committed to the integrity and quality of the clinical studies 
it coordinates and implements.  The University of Chicago will ensure that the legal and 
ethical obligations associated with the conduct of clinical research involving human 
subjects are met.   
 
As the Department of Health and Human Services continues to strengthen procedures 
for human subjects’ protections via new regulations, The University of Chicago will 
review these evolving standards in relation to the proposed activities and will advise the 
investigators on those that may apply. 
 
In addition, The University of Chicago has a Federal wide Assurance (FWA) number on 
file with the Office for Human Research Protections (OHRP).   
 
This assurance commits a research facility to conduct all human subjects’ research in 
accordance with the ethical principles in The Belmont Report and any other ethical 
standards recognized by OHRP.  Finally, per OHRP regulations, the research facility will 
ensure that the mandatory renewal of this assurance occurs at the times specified in the 
regulations. 
 
Institutional Review Board 
 
The University of Chicago IRB will review this protocol and all protocol-related 
documents and procedures as required by OHRP and local requirements before subject 
enrollment. The University of Chicago IRB currently holds and will maintain a US FWA 
issued by OHRP for the entirety of this study. 
 
Informed Consent Process 
 
The informed consent process will be initiated before a volunteer agrees to participate in 
the study and should continue throughout the individual’s study participation. The 
subject will sign the informed consent document before any procedures are undertaken 
for the study. A copy of the signed informed consent document will be given to the 

Version 20May2020 
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subject for their records. The consent will explain that subjects may withdraw consent at 
any time throughout the course of the trial. Extensive explanation and discussion of 
risks and possible benefits of this investigation will be provided to the subjects in 
understandable language. Adequate time will be provided to ensure that the subject has 
time to consider and discuss participation in the protocol.  
 
The consent will describe in detail the study interventions/products/procedures and 
risks/benefits associated with participation in the study. The rights and welfare of the 
subjects will be protected by emphasizing that their access to and the quality of medical 
care will not be adversely affected if they decline to participate in this study. 
 
Informed Consent Process for Legally authorized representative (LAR) or 
appropriately identified surrogate 
 
Informed consent will be discussed and obtained in the subject's private hospital room 
before any screening procedures take place. 
 
For decisionally impaired individuals, the study staff will carry out the consent 
discussion by phone or over video chat with the LAR or appropriately identified 
surrogate.  
 
Consent documents will be mailed/faxed or emailed to the (LAR) or appropriately 
identified surrogate initially. After the discussion and consent process take place, the 
consent documents which are signed and dated by the LAR or appropriately identified 
surrogate will be sent back to the study team. The consent document that is signed by 
the LAR or appropriately identified surrogate may be received in the following manners: 
faxed copy, scanned copy or email. The study team will then send the LAR or 
appropriately identified surrogate a fully executed copy of the consent to the LAR or 
appropriately identified surrogate for their records.  
 
If needed, a walk-out and meet approach could be used for those LAR or appropriately 
identified surrogate s who do not have the capabilities to receive/send documentation 
electronically. 
 
Consent discussion and execution will be done by Dr. Madariaga or a member of the 
research team. 
 
Subject Confidentiality 
 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, 
and the sponsors and their agents. No information concerning the study or the data will 
be released to any unauthorized third party without prior written approval of the sponsor. 
The results of the research study may be published, but subjects’ names or identifiers 
will not be revealed.  Records will remain confidential.  To maintain confidentiality, the 
PI will be responsible for keeping records in a locked area and results of tests coded to 
prevent association with subjects’ names.  Data entered into computerized files will be 

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accessible only by authorized personnel directly involved with the study and will be 
coded.  Subjects’ records will be available to the FDA, the NIH, investigators at the site 
involved with the study, and the IRB. 
 
Future Use of Stored Specimens 
 
Subjects will be asked for consent to use their samples for future testing before the 
sample is obtained.  The confidentiality of the subject will be maintained. They will be no 
plans to re-contact them for consent or to inform them of results.  The risk of collection 
of the sample will be the small risk of bruising or fainting associated with phlebotomy 
however these samples will be taken at the same time as other protocol required 
samples. 
 
No human genetic testing will be performed on the samples.   
 
Five ml of blood samples will be collected at 5 time points (See Schedule of Events).  
Serum will be frozen in 1-ml aliquots. These samples will be used to answer questions 
that may arise while the study is underway or after it is completed.  If for instance, there 
were unanticipated AEs, serum could be used to run tests that might help determine the 
reason for the AEs.  Cytokines could be measured, for example. 
 
Samples would not be shared with investigators other than investigators at the 
University of Chicago unless outside investigators had relevant assays or expertise not 
available to the study investigators. The specimens would remain linked and at 
University of Chicago for 5 years. Any use of these specimens not specified in the 
current protocol will be reviewed by the University of Chicago IRB. 
 
Data management and monitoring 
 
Source Documents 
 
The primary source documents for this study will be the subjects’ medical records. If the 
investigators maintain separate research records, both the medical record and the 
research records will be considered the source documents for the purposes of auditing 
the study. The investigator will retain a copy of source documents. The investigator will 
permit monitoring and auditing of these data, and will allow the sponsor, IRB and 
regulatory authorities access to the original source documents. The investigator is 
responsible for ensuring that the data collected are complete, accurate, and recorded in 
a timely manner. Source documentation (the point of initial recording of information) 
should support the data collected and entered in to the study database and must be 
signed and dated by the person recording and/or reviewing the data. All data submitted 
should be reviewed by the site investigator and signed as required with written or 
electronic signature, as appropriate. Data entered into the study database will be 
collected directly from subjects during study visits or will be abstracted from subjects’ 
medical records. The subjects’ medical records must record their participation in the 
clinical trial and what medications (with doses and frequency) or other medical 

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interventions or treatments were administered, as well as any AEs experienced during 
the trial. 
 
Data Management Plan 
 
Study data will be collected at the study site(s) and entered into the study database. 
Data entry is to be completed on an ongoing basis during the study. 
 
Data Capture Methods 
 
Clinical data will be entered into a database which includes password protection and 
internal quality checks to identify data that appear inconsistent, incomplete, or 
inaccurate. 
 
Study Record Retention 
 
The PI is responsible for retaining all essential documents listed in the ICH GCP 
Guidelines. The FDA requires study records to be retained for up to 2 years after 
marketing approval or disapproval (21 CFR 312.62), or until at least 2 years have 
elapsed since the formal discontinuation of clinical development of the investigational 
agent for a specific indication. These records are also to be maintained in compliance 
with IRB/IEC, state, and federal medical records retention requirements, whichever is 
longest. All stored records are to be kept confidential to the extent provided by federal, 
state, and local law. It is the site investigator’s responsibility to retain copies of source 
documents until receipt of written notification to the sponsor. 
 
No study document should be destroyed without prior written agreement between the 
sponsor and the Principal Investigator. Should the investigator wish to assign the study 
records to another party and/or move them to another location, the site investigator 
must provide written notification of such intent to sponsor with the name of the person 
who will accept responsibility for the transferred records and/or their new location. The 
sponsor must be notified in writing and written permission must be received by the site 
prior to destruction or relocation of research records. 
 
 
 
 

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https://www.medrxiv.org/content/10.1101/2020.03.16.20036145v1.full.pdf 
 
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https://www.nationalacademies.org/news/2020/statement-from-the-presidents-of-the-
nas-nae-and-nam-supporting-steps-necessary-to-assess-the-potential-for-human-
convalescent-plasma-to-help-control-covid-19  
 
http://www.aabb.org/advocacy/regulatorygovernment/Documents/COVID-19-
Convalescent-Plasma-Resources.pdf 
 
https://www.fda.gov/media/136470/download 
 
https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-
exemption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-
inds 
 
https://ccpp19.org/