A Phase IIb Clinical Trial to Evaluate the Efficacy, Safety and Immunogenicity of Two Doses of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) in Adults 18 Years of Age and Older, Living With HIV.
Phase: PHASE2
Conditions: Covid19
Sponsor: Fundación Huésped

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Clinical Trial Protocol 
 
 
Study Sponsor: 
 
Fundación Huésped  
Primary Study 
Product 
Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 
(Ad5-nCoV) 
 
 
Date of protocol 
September 10th, 2021 
Version 
1.5 
Title 
Phase IIb Trial of Recombinant Novel Coronavirus Vaccine (Adenovirus 
Type 5 Vector) (Ad5-nCoV) in Adults 18 years of age and older, living 
with HIV 
Detailed Title 
A phase IIb clinical trial to evaluate the efficacy, safety and 
immunogenicity of two doses of Recombinant Novel Coronavirus 
Vaccine (Adenovirus Type 5 Vector) in adults 18 years of age and older, 
living with HIV. 
 
Protocol Number 
FH-58 (AD5NCOV-HIV2b) 
Registration Number TBD 
 
Principal 
Investigator 
 
 
Dr. Pedro Enrique Cahn, MD, PhD 
Director, Fundación Huésped 
Carlos Gianantonio 3932 (ex Pje. Ángel Peluffo) C1202ABB, Buenos 
Aires, Argentina  
Telephone:(5411) 49817777 
Fax: (5411) 49824024 
E-mail: pedro.cahn@huesped.org.ar 
 
 

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Global Co-Principal 
Investigator 
Scott A Halperin, MD 
Canadian Center for Vaccinology 
Dalhousie University/IWK Health Centre 
5850/5980 University Avenue 
Halifax, NS B3K 6R8, Canada 
Telephone: 902-470-8141 
Fax: 902-470-7232 
Email: scott.halperin@dal.ca 
 
Study Statisticians 
Bruce Smith, PhD 
Canadian Center for Vaccinology 
Dalhousie University/IWK Health Centre 
5850/5980 University Avenue 
Halifax, NS B3K 6R8, Canada 
Telephone: 902-470-8141 
Fax: 902-470-7232 
Email: bruce.smith@dal.ca 
 
Lingyun Ye, MSc 
Canadian Center for Vaccinology 
Dalhousie University/IWK Health Centre 
5850/5980 University Avenue 
Halifax, NS B3K 6R8, Canada 
Telephone: 902-470-8141 
Fax: 902-470-7232 
Email: Lingyun.Ye@iwk.nshealth.ca 
 
Study Sponsor 
Scientific and 
Medical Affairs 
Contact 
 
 
Luis Barreto, MD 
Senior Scientific Advisor and member of the Scientific Advisory Board 
CanSino Biologics, Inc. 
185 South Avenue 
TEDA West, Tianjin, China 300462 
Telephone: 416-294-5840 
Email: drluisbarreto@gmail.com 
 
Study Financial 
Sponsor Contact  
Tao Zhu, PhD 
CanSino Biologics Inc.  
185 South Avenue, TEDA West 
Tianjin, China 300462 

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Protocol Medical 
Writer  
 
 
Tel:+86 13951994867 
E-mail: tao.zhu@cansinotech.com  
 
Laura Leppan, BScN, RN  
Canadian Center for Vaccinology  
Dalhousie University/IWK Health Centre 
5850/5980 University Avenue.  
Email: leppanlaura@gmail.com 

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STATEMENT OF COMPLIANCE 
Signature Page of Sponsor’s Approval for the Clinical Trial Protocol 
 
Brief Title 
Phase IIb trial of Recombinant Novel Coronavirus Vaccine (Adenovirus 
Type 5 Vector) (Ad5-nCoV) in adults 18 years of age and older, living 
with HIV 
Official Title  
A phase IIb clinical trial to evaluate the efficacy, safety and 
immunogenicity of two doses of Recombinant Novel Coronavirus 
Vaccine (Adenovirus Type 5 Vector) in adults 18 years of age and older. 
Vaccine 
Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 
(Ad5-nCoV) 
 
Protocol Number 
FH-58 (AD5NCOV-HIV2b) 
Protocol Date 
September 10th, 2021 
Version No. 
1.5 
 
Sponsor 
 
Fundación Huésped 
 
Sponsor Person In 
Charge 
 
Pedro Cahn, MD, PhD 
Fundación Huésped 
Carlos Gianantonio 3932, CABA, Argentina C1202ABB 
Telephone +54 9 11 49817777 
Email: pcahn@hhuesped.org.ar 
 
Sponsor Person in Charge 
Signature:  
 
Date: 
 
 
 
 
 
 
 
 
 
 
 

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Statement of PI 
I agree to: 
Take the full responsibilities as Global Principal Investigator (PI) of this clinical trial. Ensure 
that this clinical trial is conducted according to this approved protocol, or revised protocol, and 
the clinical trial SOPs from the sponsors. 
Ensure that the investigators participating in this clinical trial understand the product information 
of the investigational vaccine provided by the Sponsors, and understand the duties and 
responsibilities related to the clinical trial as outlined in this clinical trial protocol. 
Ensure that there are no changes to the clinical trial protocol without the review and written 
approval of the sponsors and the Institutional Review Board (IRB) unless it is due to urgent 
removal of immediate damages to the participants or due to the regulatory requirements (such as 
due to administration requirements). 
That I fully understand the correct usage methods of the investigational vaccine, and I fully 
understand the information provided by the sponsors, including but not limited to the following: 
Current Investigator Brochure [10] or equivalent documents. 
I am familiar with and will comply with the requirements of Good Clinical Practices (GCP) and 
other relevant regulatory requirements. 
 
Brief Title 
Phase IIb trial of Recombinant Novel Coronavirus Vaccine (Adenovirus 
Type 5 Vector) (Ad5-nCoV) in adults 18 years of age and older, living with 
HIV 
 
Protocol Number 
 
FH-58 (AD5NCOV-HIV2b) 
Protocol Date 
September 10th, 2021  
Version No. 
1.5 
 
Principal 
Investigator 
 
Dr. Pedro Enrique Cahn, MD, PhD 
Signature: 
 
 
 
 
 
Date: 
 

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Statement of Global Co-PI 
I agree to: 
Take the full responsibilities as Global Principal Investigator (PI) of this clinical trial. Ensure 
that this clinical trial is conducted according to this approved protocol, or revised protocol, and 
the clinical trial SOPs from the sponsors. 
Ensure that the investigators participating in this clinical trial understand the product information 
of the investigational vaccine provided by the Sponsors, and understand the duties and 
responsibilities related to the clinical trial as outlined in this clinical trial protocol. 
Ensure that there are no changes to the clinical trial protocol without the review and written 
approval of the sponsors and the Institutional Review Board (IRB) unless it is due to urgent 
removal of immediate damages to the participants or due to the regulatory requirements (such as 
due to administration requirements). 
That I fully understand the correct usage methods of the investigational vaccine, and I fully 
understand the information provided by the sponsors, including but not limited to the following: 
Current Investigator Brochure [10] or equivalent documents. 
I am familiar with and will comply with the requirements of Good Clinical Practices (GCP) and 
other relevant regulatory requirements. 
 
Brief Title 
Phase IIb trial of Recombinant Novel Coronavirus Vaccine (Adenovirus 
Type 5 Vector) (Ad5-nCoV) in adults 18 years of age and older, living with 
HIV 
 
Protocol Number 
 
FH-58 (AD5NCOV-HIV2b) 
Protocol Date 
September 10th, 2021 
Version No. 
1.5 
 
Principal 
Investigator 
 
Dr. Scott A Halperin, MD 
Signature: 
 
 
 
 
 
Date: 
 
 

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STUDY SYNOPSIS 
 
Study Title 
Phase IIb trial of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (Ad5-
nCoV) in adults 18 years of age and older, living with HIV. 
Full Title 
A phase IIb clinical trial to evaluate the efficacy, safety and immunogenicity of two doses of 
Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) in adults 18 years of age and 
older, living with HIV. 
Objectives 
Primary Safety Objectives:  
● Evaluate the incidence of solicited adverse reactions within 7 days after vaccination.  
● Evaluate the incidence of unsolicited adverse events within 28 days after vaccination. 
● Evaluate the HIV viral load 24 and 52 weeks after vaccination 
● Evaluate the incidence of serious adverse events (SAE) and medically attended adverse 
events (MAE) within 52 weeks after vaccination in all participants.  
Primary Immunogenicity Objectives:  
● Evaluate the seroconversion rate of S-RBD IgG antibody on Day 28, Day 84 and Week 24 
and Week 52 after vaccination, measured by ELISA. 
● Evaluate the immunogenicity of two doses of the vaccine. 
Secondary Safety Objectives: 
● Evaluate the incidence of a decrease in CD4+ cell count by ≥20% at 24 and 52 weeks after 
vaccination. 
● Evaluate changes in the CD4/CD8 ratio at 24 and 52 weeks compared to the basal value. 
● To evaluate the efficacy of two doses of Ad5-nCoV in different age groups from 14 and 28 
days to 24 and 52 weeks after vaccination. This will be evaluated by weekly participant 
contact to assess for any signs or symptoms of COVID 19. 
Secondary Immunogenicity Objectives: 
● Evaluate the GMT of S-RBD IgG antibody on Day 28, Day 84 and Week 24 and Week 52 
after vaccination, measured by ELISA. 
● Evaluate the GMI of S-RBD IgG antibody on Day 28, Day 84 and Week 24 and Week 52 
after vaccination, measured by ELISA. 
● Evaluate the seroconversion rate of pseudo-virus neutralizing antibody on Day 28, Day 84 
and Week 24 and Week 52 after vaccination. 
● Evaluate the GMT of pseudo-virus neutralizing antibody on Day 28, Day 84 and Week 24 
and Week 52 after vaccination. 
● Evaluate the GMI of pseudo-virus neutralizing antibody on Day 28, Day 84 and Week 24 and 
Week 52 after vaccination. 

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● Evaluate the positive rate and level of IFN-γ, TNF, IL-4, IL-5, IL-13 stimulated by peptide 
pool of S protein on Day 28, Day 84 and Weeks 24 and Week 52 after vaccination, measured 
by intracellular cytokine staining (ICS) (in a subset of approximately 50 participants). 
Exploratory Objectives  
● To evaluate the efficacy of two doses of Ad5-nCoV in preventing virologically confirmed 
(PCR positive) COVID-19 disease occurring 14 days and 28 days to 52 weeks after 
vaccination, regardless of severity.  
● To evaluate the efficacy of two doses of Ad5-nCoV in preventing virologically (PCR) or 
serologically (four-fold increase in SARS-CoV-2 anti-N IgG from pre-immunization to post 
symptom, defined as Day 21-28 post illness blood test, or pre-symptom to post-symptom 
blood test) confirmed COVID-19 disease occurring 14 and 28 days to 52 weeks after 
vaccination, regardless of severity. 
● To evaluate the efficacy of two doses of Ad5-nCoV in preventing severe COVID-19 disease 
caused by SARS-CoV-2 infection from 14 and 28 days to 24 and 52 weeks after 
vaccination. 
Severe disease is defined as: 1) Clinical signs at rest indicative of severe systemic illness 
(respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air 
at sea level or PaO2/FiO2 < 300 mm Hg), 2) Respiratory failure (defined as needing 
high-flow oxygen, non-invasive ventilation, mechanical ventilation or ECMO),  3) 
Evidence of shock (SBP < 90 mm Hg, DBP < 60 mm Hg, or requiring vasopressors), 4) 
Significant acute renal, hepatic, or neurologic dysfunction, 5) Admission to an ICU 
● Evaluate the efficacy of Ad5-nCoV in preventing asymptomatic disease of COVID-19 
(confirmed by N IgG antibody on week 52 after vaccination). 
● Evaluate the severity of COVID-19 cases among vaccine recipients (based on WHO or FDA 
criteria) as compared to the control group, to measure antibody-mediated disease 
enhancement (ADE). 
● Evaluate for any evidence of SARS-CoV-2 virus shedding in COVID-19 cases that occurred 
28 days to 52 weeks after vaccination (detection of viral nucleic acid every 2 days after being 
confirmed). 
● Perform genotyping of SARS-CoV-2 virus isolates of COVID-19 cases that occurred 28 days 
to 52 weeks after vaccination. 
● Evaluate incidence of suspected but unconfirmed cases of COVID-19 (either because of 
negative or no tests). 
Indication
 
 
Prevention of novel coronavirus disease (COVID-19) caused by infection with the SARS-CoV-2 
coronavirus. 
Target 
population 
Generally healthy adults 18 years of age and older, living with HIV 

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Sample Size 
N=500 
Rationale 
for study 
The 2019 novel coronavirus (SARS-CoV-2) is a positive non-segment single-stranded RNA virus, 
belonging to the Coronaviridae family of Nidovirales. There are six known coronaviruses in 
humans, including 229E and NL63 in the alpha genus, OC43 and HKU1 in the beta genus, Middle 
East respiratory syndrome-associated coronavirus (MERS-CoV), and severe acute respiratory 
syndrome-associated coronavirus (SARS- CoV).  
The coronavirus isolated from the lower respiratory tract of patients with unexplained pneumonia in 
Wuhan is a new type of genus β coronavirus. Following the outbreak of severe acute respiratory 
syndrome coronavirus (SARS-CoV) in 2002 and the outbreak of MERS-CoV in 2012, SARS-CoV-
2 is the third highly pathogenic coronavirus. The Coronavirus Disease 2019 (COVID-19) is caused 
by the infection of the 2019 novel coronavirus (SARS-CoV-2) started in January 2020. World 
Health Organization (WHO) declared COVID-19 a worldwide pandemic on March 12, 2020. As of 
Oct.20, 2020, there were over 42 million cases worldwide and over 1 million deaths in 185 
countries/regions [1]. China had reported 87,028 confirmed cases, the US has over 8 million cases, 
and Canada over 200,000 cases [1]. As of November 28, 2020, there were over 61.8 million cases 
worldwide and over 1.4 million deaths in 185 countries/regions [1]. The COVID-19 pandemic has 
brought heavy economic pressure, medical burden, and severe harm to people's lives and health. 
It is necessary and very urgent to develop preventive vaccines against COVID-19 to meet the global 
needs. 
The vaccine candidate Ad5-nCoV, intended to prevent the COVID-19 caused by SARS-CoV-2, is 
jointly developed by CanSino Biologics Inc. and its collaborator, the Beijing Institute of 
Biotechnology. Using the replication-deficient human adenovirus type 5 as a vector, Ad5-nCoV has 
been developed through recombinant virus construction, amplification, cell culture, purification, 
and formulation. Ad5-nCoV expresses the specific S protein of SARS-CoV-2. It is suggested that 
both humoral and cellular immune responses play an important role in protective immunity 
according to the results of pre-clinical, phase I, and phase II studies conducted by CanSino 
Biologics. This study is a phase IIb clinical trial to evaluate the efficacy, safety, immunogenicity of 
two doses of Ad5-nCoV at a dose level of 5×1010 vp in healthy adults, aged 18 years of age and 
older living with HIV. 
Testing 
Vaccine 
Study Product:          Ad5-nCoV manufactured by CanSino Biologics Inc. 
Active Ingredients: Replication-defective recombinant human type 5 adenovirus expressing S 
protein of novel coronavirus 
Excipients: 
Mannitol, sucrose, sodium chloride, magnesium chloride, polysorbate 80, 
HEPES, and glycerin 
Packaging:  
The vaccine is contained in a vial 
Specification:             0.5 mL/vial 
Dosage: 
            5x1010vp (≥4x1010vp) 

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Shelf Life:  
 
Tentatively 24 months 
Storage: 
It is recommended to store and transport at 2-8 ℃ (details of the temperature 
requirements are specified in the pharmacy manual).  
Administration: 
Intramuscular (IM) injection in the deltoid muscle of the upper arm. 
Schedule: 
A double-dose of vaccine is scheduled for all participants. A second dose of 
vaccine is scheduled for all participants at Day 56. 
 
 
 
Developers:                CanSino Biologics Inc. 
Beijing Institute of Biotechnology 
Manufacturer:  
CanSino Biologics Inc. 
Study design Summary:  
 
This Phase IIb study is a clinical trial for 500 participants 18 years of age or older living with HIV. 
All participants will receive two doses of the study vaccine and will be followed to monitor vaccine 
candidate safety, immunogenicity, and efficacy during 52 weeks. Fifty five days after the first 
vaccination, all participants will receive a second injection.  
 
Study Interventions: 
All participants will be subject to the following procedures:  
● Informed consent 
The signed informed consent must be obtained before study participation.  
● Check inclusion and exclusion criteria 
All inclusion and exclusion criteria will be checked at the screening in-person visit. 
● Collect demographic data and participant contact information.  
Record participant’s demographic data such as date of birth, sex, gender, height, weight and 
race in the participant’s eCRF. A current email addresses and or phone numbers will be 
collected for each participant. Contact information may also be used to remind participants of 
up-coming in-person visits. 
● Medical history 
Obtain the participant’s medical history by interview and/or review of the participant’s medical 
records and record any pre-existing conditions or signs and/or symptoms present in a 
participant prior to the first study injection in the eCRF. This will include reviewing any health 
condition that may prevent the participant from enrolling in the study, such as an unstable 
health condition. HIV clinical, treatment, and laboratory history will be reviewed.  
● HIV status, viral load, CD4 and CD8 counts 
● At screening visit, HIV status will be verified based on a previous serologic result or previous 
detectable viral load. HIV status can also be confirmed with a prescription for antiretroviral 
treatment or a follow-up record from your treating physician. Viral load, and CD4 and CD8 
counts samples will be collected at the first screening/baseline visit, randomization visit, and 

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week 24 and week 52 visits. Screening visit value will be used as reference value for 
comparison with further values.  
● Check contraindications, warnings and precautions to injection 
Contraindications, warnings and precautions to injection must be checked at the beginning of 
the First Injection Visit. 
● Urine Pregnancy Test/Birth Control  
Women of child-bearing age will be asked to perform a urine pregnancy test before the 
Injection Visits. The result of the urine pregnancy test must be negative in order to proceed 
with vaccine administration. In addition, participants who are able to become pregnant or could 
impregnate a partner are required to have used approved contraception for least 30 days prior to 
the study vaccination, and commit to use it for 90 days after the study vaccination. 
● Screening conclusion 
Participants will be deemed eligible to participate upon reviewing medical history and inclusion 
and exclusion criteria. This will occur prior to vaccination on First Injection Visit and will be 
verified before Second Injection. 
● Assess pre-injection vital signs (body temperature, blood pressure, pulse rate and 
respiratory rate)  
The body temperature of all participants needs to be measured prior to any study product 
administration on First and Second Injection Visits. Body temperature may be measured by any 
method (oral, axillary). If the participant has fever (fever is defined as temperature ≥38.0° C 
orally or ≥37.8 axillary) on the day of injection, the injection will be rescheduled within 1 
week. 
● Check and record prior medications and concomitant medication/injection  
Prior medications and concomitant medication/injection must be checked and recorded in the 
eCRF. Prior medications should include any medication taken by the participant within 14 days 
prior to screening. Participants will be asked to avoid over-the-counter medications such as 
antipyretics (e.g., acetaminophen) and anti-inflammatory medications (e.g., ibuprofen, 
naproxen) in the 12 hours before study vaccine receipt but will be allowed to take these over-
the-counter medications as needed to treat fever or other AE after vaccination. Usage of these 
over-the-counter medications will be recorded as concomitant medications and linked to the AE 
collected as solicited or unsolicited events, as the case may be. 
● Check and record intercurrent medical conditions 
Any medical conditions should be collected in the clinical chart and recorded in the eCRF. 
● Baseline serology 
Approximately 25 mL of whole blood will be collected from each participant at First Injection 
Visit, Day 28, Day 84, week 24 and week 52 and separated for serum. The serum will be 
aliquoted. The results of antibody testing from baseline serum will not be used to determine 
eligibility for enrolment; instead, results will solely be used for analysis and comparison 
purposes. Presence of pre-existing SARS-CoV-2 antibodies found in baseline serum will be 
used for a stratified immunogenicity and efficacy sub-analysis. The second aliquot will be 

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stored as a back-up. For participants who entered in the blinded version and then were 
unblinded and vaccinated, baseline serology will not be performed again, taking the values from 
the baseline visit performed at the first visit. 
● For linking purposes, each participant will be assigned a treatment identification number. The 
number of each administered treatments must be recorded in the eCRF. 
● Injection of study vaccine  
After completing all prerequisite procedures prior to injection, one dose of the assigned vaccine 
will be administered IM in the deltoid muscle, preferable of the non-dominant arm. If the 
investigator or delegate determines that the participant’s health on the day of administration 
temporarily precludes administration, the visit will be rescheduled within 1 week. There will be 
a 15-minute wait after each vaccination to monitor for any rare anaphylactic reaction. At Day 
56 after first vaccination, all participants will get a second injection of the investigational 
vaccine (Second Injection Visit) 
● Safety participant contacts 
Every 4 Weeks for 52 weeks there will be telephone calls following vaccination. They will be 
used to continuously collect any SAE and MAE data. Participants can report any AE they 
experience at any time during the study period; however, only SAE and MAE will be entered 
into the eCRF. In-person visits will occur for Day 28 visit (to collect solicited and unsolicited 
events, Day 56 (Second Injection Visit), Day 84 and Week 24, and Week 52 visits.  
● Efficacy participant contacts 
All participants will have efficacy participant contacts weekly, for 52 weeks following 
vaccination. There will be approximately 52 efficacy participant contacts. All efficacy 
participant contacts will be emails, although other methods such as phone calls or text 
messages, if preferred, are acceptable. Each participant contact needs to be recorded in the study 
electronic case report form. The purpose of these participant contacts is to ask if the participants 
had any symptoms of illness they may be experiencing, regardless of severity. Any possible 
COVID-19 relevant symptoms will trigger laboratory testing for SARS-CoV-2 infection. 
 
● Illness participant contact visits (Confirmed or suspected infection during study) 
Participants will be provided detailed instructions regarding the signs and symptoms of 
COVID-19 disease at each participant contact and will be instructed to seek medical attention 
and notify study staff should symptoms occur. Symptoms of interest include fever, cough, 
difficulty breathing, diarrhea, nausea, vomiting, prolonged fatigue, respiratory symptoms, chills, 
myalgia, sore throat, headache, congested/runny nose, pneumonia, difficulty swallowing, 
anosmia/ageusia (loss of sense of smell/taste), and neurological events. 
During the observation period of the study, if any of these symptoms develop in a participant, 
he/she should immediately follow local procedures for care of suspected COVID-19 illness and 
contact the study team. If a COVID-19 infection is found during the study, a case investigation 
will be undertaken according to locally recommended procedures. 

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● If COVID-19 is suspected, the participant will have a nasopharyngeal/throat swab taken.  
Testing for COVID-19 by PCR will be performed at the local clinical laboratory.   
● If negative, the test will be repeated in 3 days from the first testing day.   
● All attempts will be made to re-test positive samples in a reference laboratory. If the local lab is 
also a reference laboratory, then a confirmatory sample is not required. 
● If the PCR is positive, nasopharyngeal/throat swabs will be taken every 2 days times 3 and then 
weekly and tested for COVID-19 by PCR until a negative sample is obtained.   
● A serum sample (10mL blood) will be collected at the time of illness presentation and testing 
for SARS-CoV-2 anti-N IgG antibodies will be performed at Nexelis Laboratories (Canada). 
● At Day 21-28 post-illness, a second serum sample will be taken and sent to the central 
laboratory for anti-N IgG. 
● Participants who were PCR negative will also have that visit on day 21-28, where they will be 
tested for SARS-CoV-2 antibodies (Nexelis Laboratories (Canada)). This visit takes place at 
the research site where the participant is enrolled.  
● Participants who develop COVID-19 infection post-vaccination will be carefully monitored for 
vaccine-related disease enhancement in collaboration with their primary physician who will be 
encouraged to obtain specimens in accordance with the Brighton Collaboration definition 
(Munoz, 2020), including a serum sample tested locally for C-reactive protein (CRP), ferritin, 
and procalcitonin, biomarkers that have been associated with predicting more severe disease 
outcome in infected patients. 
 
Participants who develop COVID-19 disease will continue to be followed for other study outcomes 
by telephone while in isolation, and at the study site once recovered and released from isolation by 
public health officials. 
 
● Final serology 
Approximately 25mL of whole blood will be collected and will then be separated into serum at 
week 52. The serum will be aliquoted. The first aliquot will measure anti-N IgG antibodies, at 
the Nexelis Laboratories (Canada). The second aliquot will be stored as a back-up. The one-
year antibody levels measured against anti-N IgG antibodies will be compared to the 
participant’s baseline levels to evaluate the exploratory efficacy analysis against asymptomatic 
infection. 
● E-diary and Diary Cards 
Participants will be provided with access to an e-diary and a thermometer, and instructions 
about how to use them. A paper diary card may be available if required by the study site. 
Participants will be asked to record solicited AE for 7 days after receiving the vaccination, and 
unsolicited AE for 28 days in their diary. A second e-diary or a paper diary will be provided at 
Day 56 and will be collected at Day 84 visit. The completed e-diary and diary cards will be 
reviewed and data collected at the 28-Day safety in-person visit. Non completion of the e-diary 

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or diary cards will be investigated with the participant through telephone call(s) or any other 
convenient procedure. All data collected from the e-diary and diary cards will be uploaded into 
the eCRF. 
● Immunogenicity in-person visit 
1. Blood collection for ELISA and pseudo-virus neutralization antibody measurement 
Approximately 25mL of whole blood will be collected on First Injection Visit, Day 
28, Day 84, Week 24, and Week 52, as described above. These in-person visits will 
occur at the participant’s local study site. Serum will be separated into two aliquots. 
A baseline antibody titer against SARS-CoV-2 will be established from the blood 
sample collected on First Injection Visit, as outlined in the “baseline serology” 
description. In addition, these samples will also be used to evaluate for additional 
immunogenicity objectives including: the seroconversion rate of S-RBD IgG 
antibody, GMT of S-RBD IgG antibody, GMI of S-RBD IgG antibody, 
seroconversion rate of pseudo-virus neutralizing antibody, GMT of pseudo-virus 
neutralizing antibody, and the GMI of pseudo-virus neutralizing antibody at Day 28, 
Day 84, Week 24, and Week 52. The second aliquot will be stored as a back-up. 
2. Blood collection for ICS measurement  
In a subset of approximately 50 participants, approximately 30mL of whole blood will 
be collected. Collections will occur on First Injection Visit (baseline), just prior to 
vaccination, and on Day 28, Day 84, and at 24 and 52 weeks post-vaccination.  TNF, 
IL-4, IL-5, IL-13 will be measured by ICS on Day 28, Day 84 and Weeks 24 and 52 
after vaccination. PBMC will be shipped on liquid nitrogen to Nexelis Laboratories 
(Canada).  
Study duration: 
Total duration of this trial from the enrolment to the last visit will be approximately one year (52 
weeks). 
Visit plan 
All participants will have at least 6 (six) planned in-person visits on Screening visit/First Injection 
Visit and Day 28, Day 56 (Second Injection Visit), Day 84, Week 24, and Week 52. The 
Screening/baseline visit will entail reviewing the ICF, completing a medical history of the 
participant, reviewing inclusion and exclusion criteria, and collecting a blood sample for HIV viral 
load and CD4/CD8 counts. A baseline SARS-CoV-19 antibody (Nexelis Laboratories), and a urine 
pregnancy test in women of child-bearing potential will be performed. The vaccine will be 
administered after having the negative result on the pregnancy test. Participants are required to 
remain at the study site for a minimum of 15 minutes after receiving the vaccine to monitor for any 
vaccine-related AE.  
 
Participants will be given access to an e-diary or paper diary card to record solicited AE from First 
Injection Visit- day 7 and unsolicited AE from First Injection Visit- day 28. The data in the 
completed e-diary or diary card will be reviewed and data will be collected on Day 28.  
 

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A new e-diary or paper diary card to record solicited and unsolicited AE from Second Injection will 
be provided at Second Injection Visit- Day 56. The data in the completed e-diary or diary card 
provided during the Day-56 visit will be reviewed and data will be collected at visit on Day 84. 
 
Further details are outlined in Section 3.7 and 5.1. 
 
All participants will be contacted on a weekly basis to be reminded to report any signs or symptoms 
of illness to study staff. Participants will either be contacted by the site weekly, or they will receive 
an automated message (email) with a link to answer questions about whether or not they had an 
SAE, an MAE or COVID-19 symptoms. Participants will also be asked on their day 7 contact about 
any events that might meet a pause or early termination criterion. The reporting and monitoring of 
any participant illness are consistent with meeting the primary efficacy objective. If a participant 
becomes ill, they will be asked to immediately proceed to the site designated by their local study 
team where they will be assessed and treated as deemed appropriate. Participants will also receive a 
telephone call every 4 weeks, to evaluate for the incidence of any SAE or MAE.  
 
A subset of 50 participants will have additional immunologic testing performed, following the same 
visit schedule, to evaluate T-cell response to the Ad5-nCoV vaccine.  
 
If a participant demonstrates signs or symptoms of illness, an unplanned in-person visit may occur 
for evaluation and possible treatment. If, for any reason following an electronic participant 
contact, the investigator would like to conduct an in-person visit (at home or at the site) with a 
participant, they may do so at their discretion. 
Pause and 
early 
termination  
Study Suspension Criteria 
If a suspension criterion is met, the study will be put on hold, and further injections will not occur 
until a safety review has been conducted. Should a suspension criterion be met, the local PI will 
inform the PIs, Sponsors, and NRA within 24 hours.  
Suspension criteria includes:  
Grade 3 or greater AE occurring in >15% of participants will constitute study suspension criteria. 
To be included as suspension criteria, AE must begin within three days after study injection (day of 
injection and 2 subsequent days) and persist at Grade ≥ 3 on three consecutive days, depending 
upon symptom severity and kinetics. 
A suspected, unexpected serious adverse reaction (SUSAR) that is life-threatening or results in 
death will warrant study suspension. 
Other study suspension criteria include if the IDMC assessed the potential safety risks to be 
harmful, or if the vaccine candidate might be ineffective. 
 
Study Early Termination Criteria 
● Required by the sponsor, or 

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● Required by the regulatory authority, or 
● Required by an institutional review board (IRB) 
Process of Suspension of Injection and/or Study Modification 
In the event that a safety signal is observed, the IDMC might recommend that the sponsor suspend 
injections of all group participants (early termination of study) or selected groups. 
In this case, for impacted groups: 
Participants who are already injected will continue all visits as planned. 
Participants who signed an informed consent but have not received any study product will be 
informed that their study participation will be stopped. 
Statistical 
analysis 
Statistical Analysis Plan (SAP) 
 
Analysis of Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized overall and then by treatment group 
using appropriate descriptive statistics. Continuous data will be summarized using the number of 
observations, mean, standard deviation, median, minimum and maximum. Categorical data will be 
summarized using frequency counts and percentages. 95% confidence intervals will be reported, 
but no statistical hypothesis testing will be conducted. Results will be presented for all participants. 
 
Analysis of Efficacy 
Due to limited sample size, no formal efficacy hypothesis will be tested as primary objective. A 
listing of baseline characteristics, treatment group and outcome for virologically confirmed (PCR 
positive) COVID-19 cases will be produced. An exploratory efficacy analysis of Ad5-nCoV in 
preventing asymptomatic disease of COVID-19 will be conducted at the end of the study.  
 
Safety Analysis 
Primary Safety Endpoint: 
● The incidence of solicited adverse reactions within 7 days after vaccination.  
● The CD4 / CD8 ratio delta compared to baseline. 
● The incidence of unsolicited adverse events within 28 days after each vaccination. 
● The incidence of detectable HIV viral load 24 and 52 weeks after vaccination 
● The incidence of serious adverse events (SAE) and medically attended adverse events 
(MAE) within 52 weeks after vaccination in all participants.  
Data from all participants will be used to assess the primary safety endpoint. 
 
Secondary Safety Objective Endpoints 
● The incidence of a decrease in CD4+ cell count by ≥20% at 24 and 52 weeks after 
vaccination  

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All SAEs and MAEs will be listed and summarized by groups.  
 
For each participant, the individual local events will be aggregated into a combined event “Local”, 
which is the maximum severity of the individual local events. For each participant, the individual 
general events will be aggregated into a combined event “General”, which is the maximum severity 
of the individual general events.  
 
An aggregate event “Any” will be defined as the maximal severity of the combined events “Local” 
and “General”. In addition to being graded for severity as mild, moderate or severe, the severity of 
all events will be graded as "Any", which will include mild, moderate or severe events, and 
"Significant" which will include moderate or severe events. 
 
All statistical tests on safety performed will be 2-sided with Type I error of 5%.  
 
Missing values will not be included in the safety analyses, and there will be no imputation of 
missing values. No adjustments will be made for multiple comparisons. 
 
For the analysis of proportions, binomial point estimates and exact binomial confidence intervals 
will be calculated. 
 
Fisher’s Exact Test will be used to assess differences in rates of adverse events between treatment 
and control groups.  
 
In addition, all safety data will be analysed descriptively, including unsolicited events collected 
through the end of the observation period.  
 
Immunogenicity Analysis 
Primary Immunogenicity Endpoints: 
● The seroconversion rate of S-RBD IgG antibody on Day 28, Day 84 and Week 24 and Week 
52 after vaccination, measured by ELISA. 
● Evaluate the immunogenicity of one versus two doses of the vaccine 
 
Secondary Immunogenicity Endpoints: 
● GMT of S-RBD IgG antibody on Day 28, Day 84 and Week 24 and Week 52 after vaccination, 
measured by ELISA. 
● GMI of S-RBD IgG antibody on Day 28, Day 84 and Week 24 and Week 52 after vaccination, 
measured by ELISA. 
● Seroconversion rate of pseudo-virus neutralizing antibody on Day 28, Day 84 Week 24 and 

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Week 52 after vaccination. 
● GMT of pseudo-virus neutralizing antibody on Day 28, Day 84 and Week 24 and Week 52 
after vaccination. 
● GMI of pseudo-virus neutralizing antibody on Day 28, Day 84 and Week 24 and Week 52 
after vaccination. 
● Positive rate and level of IFN-γ stimulated by peptide pool of S protein on Day 28, Day 84 
and Weeks 24 and Week 52 after vaccination, measured by ELISpot. 
● Positive rate and level of IL-2, IL-4, IL-13, and IFN-γ stimulated by peptide pool of S protein 
on days 28, Day 84 and Week 24 and Week 52 after vaccination, measured by intracellular 
cytokine staining (ICS). 
 
Geometric mean antibody titers (GMTs) and GMI’s and their two side 95% confidence intervals 
will be calculated by group. Analyses will be performed on the logarithmically (base 10) 
transformed values. Individual titers below the detection limit will be set to half the limit. 
 
For the analysis of proportions, binomial point estimates and exact binomial confidence intervals 
will be calculated for each group. Rates will be compared between groups using Fisher’s exact 
tests, and geometric means will be compared using t-tests. 
 
All statistical tests performed for immunogenicity will be 2-sided with Type I error rate of 5%.  
Missing values will not be included in the immunogenicity analyses, and there will be no 
imputation of missing values. No adjustments will be made for multiple comparisons. 
The immunogenicity analysis will be carried out on both intention-to-treat and per-protocol cohorts.   
 
Exploratory Objective Endpoints 
● Efficacy of two doses of Ad5-nCoV in preventing symptomatic disease of COVID-19 
(confirmed by PCR) occurring 14 and 28 days to 52 weeks after vaccination, regardless of 
severity. 
● Efficacy of two doses of Ad5-nCoV in preventing virologically (PCR) or serologically 
(four-fold increase in SARS-CoV-2 anti-N IgG from pre-immunization to post symptom, 
defined as Day 21-28 post illness blood test, or pre-symptom to post-symptom blood test) 
confirmed COVID-19 disease occurring 14 and 28 days to 52 weeks after vaccination, 
regardless of severity. 
● Efficacy of Ad5-nCoV in preventing severe COVID-19 disease caused by SARS-CoV-2 
infection from 14 and 28 days to 24 and 52 weeks after vaccination. 
● Efficacy of Ad5-nCoV in preventing asymptomatic disease of COVID-19 (confirmed by N 
IgG antibody on week 52 after vaccination). 
● Severity of COVID-19 cases among vaccine recipients (based on WHO or FDA criteria) as 
compared to the control group, to measure antibody-mediated disease enhancement (ADE). 

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● SARS-CoV-2 virus shedding in COVID-19 cases that occurred 28 days to 52 weeks after 
vaccination (detection of viral nucleic acid every 2 days after being confirmed). 
● Genotype of SARS-CoV-2 virus isolates of COVID-19 cases that occurred 28 days to 52 
weeks after vaccination. 
● Suspected but unconfirmed cases of COVID-19 (either because of negative or no tests) 
● Evaluate incidence of suspected but unconfirmed cases of COVID-19 (either because of 
negative or no tests). 
Analysis of exploratory endpoints  
Analysis of exploratory endpoints will be descriptive. PCR confirmed positive subjects will be 
classified as having severe or non-severe disease. Severity of disease, SARS-CoV-2 virus shedding 
and Genotypes SARS-CoV-2 virus isolates will be listed by subject and date, along with 
demographic data, including the study centre. Suspected but unconfirmed cases and asymptomatic 
cases will also be listed.    
 
Final Analysis 
Immunogenicity analyses will be carried out using according-to-protocol cohorts in addition to 
intention-to-treat cohorts. 
Inclusion 
criteria 
Inclusion Criteria  
● Adults of 18 years of age, and older.  
● Confirmed HIV infection defined by: A positive rapid test or ELISA and/or a plasma HIV-1 
viral load >1000 copies/ml or rapid test or ELISA plus a positive Western Blot test. In 
patients on antiretroviral treatment, a medical history summary or antiretroviral prescription 
signed and stamped by the treating physician is acceptable. 
● Able and willing (in the Investigator’s opinion) to comply with all study requirements. 
● Willing to allow the investigators to discuss the volunteer’s medical history with their 
General Practitioner/personal doctor and access all medical records when relevant to study 
procedures. 
● Healthy adults, or stable-healthy adults who may have a pre-existing medical condition that 
does not meet any exclusion criteria.  A stable medical condition is defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease during the 3 
months before enrolment [4]. 
● For subjects of childbearing potential only: Willingness to practice continuous effective 
contraception (see glossary) for 30 days prior to enrolment in the study, for 90 days after 
receiving vaccination during the study, and have a negative pregnancy test on the day(s) of 
vaccinations.  
● Males participating in this study who are involved in heterosexual sexual activity must agree 
to practice adequate contraception (see glossary) and refrain from donating sperm for 90 
days after receiving the study vaccination.  
● Agreement to refrain from blood donation during the study. 

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● Provide written informed consent. 
 
Exclusion 
criteria 
Exclusion Criteria  
● Participation in any other COVID-19 prophylactic drug trials for the duration of the study. 
o Note: Participation in COVID-19 treatment trials is allowed in the event of 
hospitalization due to COVID-19. The study team should be informed as soon as 
possible. 
● Planned receipt of any vaccine (licensed or investigational), other than the study intervention, 
within 14 days before and after study vaccination. 
● Prior receipt of an investigational or licensed vaccine likely to impact on the interpretation of 
the trial data (e.g. Adenovirus vectored vaccines, any coronavirus or SARS vaccines) 
● Administration of immunoglobulins and/or any blood products within the three months prior to 
the planned administration of the vaccine candidate. 
● Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent 
severe infections and chronic use (more than 14 days) of immunosuppressant medication within 
the past 6 months. Topical steroids or short-term (course lasting ≤14 days) oral steroids are not 
an exclusion. 
● Active opportunistic infections or other AIDS-defining illness in the last six months. 
● History of allergic disease or reactions likely to be exacerbated by any component of Ad5-
nCoV 
● Any history of angioedema 
● Any history of anaphylaxis to any vaccine component 
● Pregnancy, lactation or willingness/intention to become pregnant within 90 days after receiving 
study vaccine  
● Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and 
cervical carcinoma in situ) 
● History of serious psychiatric condition likely to affect participation in the study 
● Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of 
significant bleeding or bruising following IM injections or venepuncture 
● Suspected or known current alcohol or drug dependency 
● Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, 
liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well-
controlled comorbidities are allowed) 
● History of laboratory-confirmed COVID-19 
● Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) 
or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) 
● Any other significant disease, disorder or finding which, in the opinion of the investigator, may 
significantly increase the risk to the volunteer because of participation in the study, affect the 
ability of the volunteer to participate in the study or impair interpretation of the study data. 

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LIST OF KEY ROLES 
Key Roles/Duty 
Responsible Individual 
Organization 
Sponsor 
Pedro Cahn 
Fundación Huésped. 
Carlos Gianantonio 3932, 
CABA, Argentina 
C1202ABB 
Telephone +54 9 11  49817777 
Email: pedro.cahn@huesped.org.ar 
 
 
 
 
Principal Investigator 
Dr. Pedro Enrique Cahn, 
MD; PhD 
 
 
Director, Fundación Huesped 
Fundación Huésped. 
Carlos Gianantonio 3932, 
CABA, Argentina 
C1202ABB 
Telephone +54 9 11  49817777 
Email: pcahn@huesped.org.ar 
 
 
 
Global Co-PI 
Scott A Halperin 
Canadian Center for Vaccinology 
Dalhousie University/IWK Health Centre 
5850/5980 University Avenue 
Halifax, NS B3K 6R8, Canada 
Tel: 902-470-8141 
Email:scott.halperin@dal.ca 
 
Central Safety Physician 
María Inés Figueroa 
 Fundación Huésped. 
Carlos Gianantonio3932, 
 CABA, Argentina 
C1202ABB 
Telephone +54 9 11  49817777 
Email:maria.figueroa@huesped.org.ar 
 
Central laboratory 
Luc Gagnon 
Nexelis 
525 Cartier West Blvd 
Laval QC H7V 3S8 
Canada 

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Tel: 450-239-1605  
Email: luc.gagnon@nexelis.com 
 
Central Data Manager 
Donna MacKinnon-
Cameron 
Canadian Center for Vaccinology 
Dalhousie University/IWK Health Centre 
5850/5980 University Avenue 
Halifax, NS B3K 6R8, Canada 
Tel: 902-470-8141 
Email: donna.mackinnon-
cameron@dal.ca 
 
Central Statistician 
Bruce Smith  
Canadian Center for Vaccinology 
Dalhousie University/IWK Health Centre 
5850/5980 University Avenue 
Halifax, NS B3K 6R8, Canada 
Telephone: 902-470-8141 
Email: bruce.smith@dal.ca 
 
 
 

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Table of Contents 
Signature Page of Sponsor’s Approval for the Clinical Trial Protocol 
4 
Statement of PI 
5 
Statement of Global Co-PI 
7 
STUDY SYNOPSIS 
8 
GLOSSARY OF TERMS 
3129 
1. INTRODUCTION 
3432 
1.1. Background 
3432 
1.2. Investigational vaccine 
3432 
1.3. Rationale for the study 
3634 
2. STUDY OBJECTIVES 
3836 
2.1 Primary Objectives 
3836 
2.2 Secondary Objectives 
3836 
3. STUDY DESIGN 
4038 
3.1 Summary 
4038 
3.2 Study Groups 
4038 
3.3 Sampling/Study Schedule 
4139 
3.4 Procedures 
4240 
3.5 Efficacy participant contacts 
4644 
3.6 Immunogenicity In-Person Visits 
4846 
4. STUDY POPULATION 
4846 
4.1 Inclusion Criteria 
4947 
4.2 Exclusion Criteria 
4947 
4.3 Recruitment 
5149 
5. STUDY PROCEDURES AND INTERVENTIONS 
5149 
5.1 Study Intervention Descriptions 
5149 
5.2 Study conclusion 
5654 

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6. STUDY PRODUCT AND ADMINISTRATION 
5654 
6.1 Description of Study Product 
5654 
6.2. Product Oversight 
5856 
7. SAFETY 
6058 
7.1 Definitions of an adverse event 
6058 
7.2 Detection of adverse events 
6361 
7.3 Participant contact of adverse events and serious adverse events 
6967 
7.4 Treatment of adverse events 
7068 
8. PARTICIPANT COMPLETION AND WITHDRAWAL 
7068 
8.1 Participant completion 
7068 
8.2 Participant withdrawal 
7068 
9. OUTCOME MEASURES AND STATISTICAL METHODS 
7270 
9.2 Study Population and Analysis Sets 
7270 
9.3 Statistical Analysis 
7270 
9.3.1 Demographics and Baseline Characteristics 
7270 
9.3.2 Efficacy Analysis 
7270 
9.3.4 Immunogenicity Analysis 
7472 
9.3.5 Analysis of exploratory endpoints 
7472 
10. DATA MANAGEMENT 
7573 
10.1 General Requirements 
7573 
10.2 Electronic Data Capture System 
7674 
11. STUDY SUSPENSION CRITERIA AND SAFETY MONITORING 
7674 
11.1 Study Suspension Criteria 
7674 
11.2 Study Early Termination Criteria 
7674 
11.3 Process of Suspension of Injection and/ or Study Modification 
7674 
12. STUDY GOVERNANCE 
7775 
12.1 Study Steering Committee 
7775 

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12.2 Endpoint Review Committee 
7876 
12.3 Independent Data Monitoring Committee 
7876 
13. ETHICAL AND REGULATORY CONSIDERATIONS 
7977 
13.1 Benefits/Potential Risks 
7977 
13.2 Informed Consent Process and Documentation 
7977 
13.3 Modification of the Protocol 
7977 
13.4 Interruption of the Trial 
8078 
13.5 Confidentiality of Data and Access to Participant Records 
8078 
13.6 Monitoring 
8078 
13.7 Auditing 
8078 
13.8 Archiving 
8078 
13.9 Stipends for Participation 
8078 
13.10 Adverse Event Compensation and Insurance 
8078 
13.11 Publication Policy 
8179 
14. ADMINISTRATIVE MATTERS 
8179 
14.1 Data Entry Instructions 
8179 
14.2 Monitoring 
8179 
14.3 Record Retention 
8280 
14.4 Quality assurance 
8280 
14.5 Posting of information on publicly available clinical trial registers 
8280 
14.6 Provision of study results to investigators 
8381 
References 
8482 
 
LIST OF FIGURES AND TABLES  
Figure 1. Procedure algorithm for efficacy contacts 
 
Table 1. In-Person Visit 
 
 Table 2. Procedures for the group of participants assigned to placebo arm 

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Table 3. Adverse Event Reporting 
 
Table 4. Time frames for submitting SAE to the Research Ethics Board……………………….. 
 
 
 

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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ATP 
According-to-protocol 
BGTD 
BMI 
CCfV 
CDISC 
CI 
COVID-19 
Biologics and Genetic Therapies Directorate, Health Canada 
Body Mass Index 
Canadian Center for Vaccinology 
Clinical Data Interchange Standards Consortium  
Confidence Interval 
Corona Virus Disease 2019 
CRO 
DMP 
ECMO 
eCRF 
EDC 
ELISA 
Contract Research Organization 
Data Management Plan 
Extra-corpeal membrane oxygen 
Electronic Case Report Form 
Electronic Data Capture System 
Enzyme-linked-immunosorbent assays 
FDA 
Food and Drug Administration, United States 
FTiH 
First time in human 
GCP 
GMI 
GMT 
HAART 
Good Clinical Practice 
Geometric Mean Increase 
Geometric Mean Titer 
Highly active anti-retroviral therapy 
HIV 
ICF 
Human Immunodeficiency Virus 
Informed Consent Form 

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ICH 
ICS 
IDMC 
IRB 
IWRS 
MAE 
International Conference on Harmonization 
Intracellular Cytokine Staining 
Independent Data Monitoring Committee 
Institutional Review Board 
Interactive Web Response System 
Medically Attended AEs 
NRA 
National Regulatory Authority 
PBMCs 
PI 
Peripheral Blood Mononuclear Cells 
Principal Investigator 
IRB 
Research Ethics Board 
SAE 
SAP 
SARS-CoV-2 
SC 
Serious Adverse Event 
Statistical Analysis Plan 
Severe Acute Respiratory Syndrome Coronavirus 2 
Steering Committee 
SOP 
SUSAR 
Standard Operating Procedure 
Suspected Unexpected Serious Adverse Reaction 
TVC 
VE 
VP 
Total Vaccinated Cohort 
Vaccine Efficacy 
Viral particles 
WBC 
WHO 
White Blood Cells 
World Health Organization  

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GLOSSARY OF TERMS 
Adequate contraception: 
Adequate contraception is defined as a contraceptive 
method with a failure rate of less than 1% per year when 
used consistently and correctly and when applicable, in 
accordance with the product label, such as: 
● Abstinence from penile-vaginal intercourse, when this 
is their preferred lifestyle, 
● Oral contraceptives, either combined or progesterone 
alone, 
● Injectable progestogen, 
● Implants of etonogestrel or levonorgestrel, 
● Estrogen vaginal ring, 
● Percutaneous contraceptive patches, 
● Intrauterine device or intrauterine system, 
● Male partner sterilization prior to the female subject’s 
entry into the study, and this male is the sole partner 
for that subject (information based on interview with 
the participant on her medical history), 
● Male condom combined with a vaginal spermicide 
(foam, gel, film, cream or suppository), 
● Male condom combined with a female diaphragm, 
whether with or without a vaginal spermicide (foam, 
gel, fil, cream, or suppository), 
Adequate contraception does not apply to participants of 
childbearing potential with same sex partners, when this 
is their preferred and usual lifestyle. 
 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the 
use of a medicinal product, whether or not considered 
related to the medicinal product. 
An adverse event (AE) can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal product. 

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For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), 
abuse or misuse. 
 
 
 
Eligible: 
 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
 
Evaluable: 
 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the according-to-protocol (ATP) analysis. 
 
Investigational product: 
(Synonym of 
Investigational 
Medicinal Product) 
 
A pharmaceutical form of an active ingredient being 
tested or used as a reference in a clinical trial, including a 
product with a marketing authorization when used in a 
way different from the approved form, or when used for 
an unapproved indication, or when used to gain further 
information about an approved use.  
 
Investigator’s Brochure: 
 
Compilation of the clinical and nonclinical data on the 
investigational product(s) that are relevant to the study of 
the product(s) in human participants. 
 
Participant: 
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, as a recipient of the 
investigational product. 
 
Randomization: 
 
Process of random attribution of treatment to participants 
in order to reduce bias of selection. 
 
 

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Solicited adverse event: 
Adverse events to be recorded as endpoints in the clinical 
study. The presence/occurrence/intensity of these events 
is actively solicited from the participant or an observer 
during a specified post-administration participant contact 
period. 
 
Treatment: 
 
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or 
intended to be administered to a participant, identified by 
a unique number, according to the study randomization or 
treatment allocation. 
 

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1. INTRODUCTION 
1.1. Background 
Since emerging in December 2019, the COVID-19 outbreak was deemed a Public Health 
Emergency of International Concern (PHEIC) by the WHO on 30 January 2020. On March 11th, 
2020, COVID-19 was declared a global pandemic. As of Oct.20, 2020, there were over 42 
million cases worldwide and over 1 million deaths in 185 countries/regions [1]. The COVID-19 
pandemic has brought heavy economic pressure, medical burden, and severe harm to people's 
lives and health. 
Currently, about 250 candidate vaccines against SARS-CoV-2 are in development worldwide, 
including mRNA vaccines, replicating or non-replicating viral vectored vaccines, DNA vaccines, 
autologous dendritic cell-based vaccine, and inactive virus vaccines [2].  
One recently published trial in the UK investigated the use of a chimpanzee adenovirus-vectored 
vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein [3]. This phase I/II 
single-blind, randomised, multi-site-controlled trial administered healthy adults (ages 18-55) 
with a 5 × 1010 viral particles (vp) dose of ChAdOx1 nCoV-19 or a control vaccine of 
meningococcal conjugate vaccine, at a 1:1 ratio. This candidate vaccine was found to be 
tolerable and immunogenic in healthy adults. Results demonstrated an increase in antibodies 
against SARS-CoV-2 spike protein in the ChAdOx1 nCoV-19 group, with levels peaking at Day 
28 after vaccination, lasting until Day 56 in participants who received a single dose, and 
continuing to increase in participants who received a booster dose. An increase in cellular 
immune response was also demonstrated in the ChAdOx1 nCoV-19 group. Participants who 
received two doses of ChAdOx1 nCoV-19 demonstrated the highest humoral and cellular 
immune responses. The results of their phase I/II trial support moving forward with a large-scale 
phase III trial. Currently, there are 11 vaccines in phase III trials including three that have 
reported interim efficacy results. 
1.2. Investigational vaccine 
The 2019 novel coronavirus (SARS-CoV-2) is a positive non-segment single-stranded RNA 
virus, belonging to the Coronaviridae family of Nidovirales. There are six known coronaviruses 
in humans, including 229E and NL63 in the alpha genus, OC43 and HKU1 in the beta genus, 
Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and severe acute 
respiratory syndrome-associated coronavirus (SARS- CoV).  
The coronavirus isolated from the lower respiratory tract of patients with unexplained pneumonia 
in Wuhan is a new type of genus β coronavirus. Following the outbreak of severe acute 
respiratory syndrome coronavirus (SARS-CoV) in 2002 and the outbreak of Middle East 
Respiratory Syndrome coronavirus (MERS-CoV) in 2012, SARS-CoV-2 is the third highly 
pathogenic coronavirus.  
 

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The vaccine candidate Ad5-nCoV, intended to prevent COVID-19 caused by SARS-CoV-2, is 
jointly developed by CanSino Biologics Inc. and the Beijing Institute of Biotechnology. Using 
the replication-deficient human adenovirus type 5 as a vector, Ad5-nCoV has been developed 
through recombinant virus construction, amplification and purification, and expresses the 
specific S protein of SARS-CoV-2. It is suggested that both humoral and cellular immune 
responses play an important role in protective immunity according to the results of pre-clinical, 
phase I and phase II studies.  
 
Pre-clinical studies showed good immunogenicity (antibodies by ELISA and neutralization, cell 
mediated immunity) in mice, guinea pigs, rats, and cynomolgus monkeys. Protection by the Ad5-
nCoV vaccine has been demonstrated in transgenic mice, ferrets and rhesus monkeys. 
Toxicology studies have been completed and have not demonstrated any concerns (see 
Investigator Brochure [10] for full details of the pre-clinical studies). 
Phase I trials found that the Ad5-vectored COVID-19 vaccine was tolerable in healthy adults [5]. 
The study was designed and carried out as a dose-escalation, single-centre, open-label, non-
randomised clinical trial. 108 healthy adults participated in the phase I portion of the study and 
were divided into low, medium, and high-dose Ad5-nCoV vaccine groups.  Participants received 
a dose on Injection visit. A total of 87% of participants reported at least 1 AE during the first 7 
days after receiving the vaccine. The most common local AE was pain at the injection site, while 
fatigue, headache and fever were the most frequently reported systemic AE. Most reported AE 
were classified as mild to moderate and were self-limiting. However, there were 5 incidences of 
a Grade 3 fever in the high dose group. There was also higher occurrence of severe fever, 
fatigue, muscle pain, or joint pain, (which might be associated with viremia caused by Ad5 
vector infection) in participants who received the of 1.5×10¹¹ viral particles. For this reason, the 
low (5×10¹⁰ vp per mL) and medium dose (1×10¹¹ vp per mL) were selected to progress to phase 
II trials. No SAE were recorded within 28 days of receiving the vaccine.  
All three doses of the Ad5-nCoV vaccine demonstrated good immunogenicity in participants [5]. 
Anti-RBD antibodies were present in all groups after Day 14 and had at least a 4-fold increase in 
97%, 94% and 100% of participants in the low, medium, and high doses respectively. Both 
ELISA and neutralizing antibodies increased significantly at 14 days post vaccination and 
peaked at 28 days post vaccination, in all three groups. A rapid T-cell response was observed in 
all groups by Day 14 as well.  
On July 20th, 2020 the Phase II results of the Ad5-nCoV clinical trial were published. 508 
healthy adults ≥ 18 years of age were randomized into three groups to receive Ad5-nCoV 
vaccine at either 1×10¹¹ vp per mL or 5×10¹⁰ vp per mL, or a placebo vaccine in a 2:1:1 ratio, 
respectively [2]. The main objectives of this study were to assess the immunogenicity and safety 
of receiving the Ad5-nCoV vaccine, and to determine the appropriate dose to be administered for 
the efficacy study (currently, phase III). 

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The data produced from the phase II clinical trial further supported the safety and tolerability of 
receiving an Ad5-nCoV vaccine in healthy adults [2]. There were no SAE recorded in any of the 
study groups within 28 days of vaccination. Participants in both the 1×10¹¹vp and 5×10¹⁰ vp 
groups commonly reported mild to moderate adverse reactions, when solicited by study staff. 
Injection site pain was the most frequently reported solicited reaction; 57% of the 1×10¹¹ vp dose 
and 56% of the 5×10¹⁰vp group reported pain within 14 days of vaccination. A total of 9% of 
participants in the 1×10¹¹vp had a Grade 3 adverse reaction, which was significantly higher than 
those who received 5×10¹⁰ vp vaccine (p=0.0011) or placebo (p=0.0004). The most commonly 
reported Grade 3 adverse reaction was a fever; however, fevers were self-limiting. There was no 
difference in the incidence of unsolicited adverse reactions between the three groups.  
Both doses of Ad5-nCoV vaccine administered in the phase II study induced a robust immune 
response to SARS-CoV-2, with overall comparable immunogenicity between the doses [2]. 
Beginning Day 14, RBD-specific ELISA antibody responses were detectable in both groups and 
peaked at 656.5 (575.2-749.2) in the 1×10¹¹vp group, and 571.0 (467.6- 697.3) in the 5×10¹⁰vp 
group, on Day 28 post vaccination. While the placebo group showed no increase in antibodies 
from baseline, 96% of the 1×10¹¹vp group and 97% of the 5×10¹⁰vp group demonstrated 
seroconversion of the RBD-specific ELISA antibodies at Day 28. There was seroconversion of 
neutralising antibodies in 59% and 47% of participants in the 1×10¹¹vp and 5×10¹⁰ vp dose 
groups, respectively. There was a significant positive T-cell response in both the 1×10¹¹vp and 
5×10¹⁰vp dose groups by Day 28, although the difference was not significant between the doses. 
A positive specific T-cell response, measured by IFNγ-ELISpot, was found in 90% of the 1×10¹¹ 
vp group and 88% of participants in the 5×10¹⁰ vp group. At Day 28, 95% of participants in the 
1×10¹¹ viral particles dose group and 91% of the recipients in the 5×10¹⁰ viral particles dose 
group showed either cellular or humoral immune responses.  
It was found that the 5×10¹⁰ vp group produced a similar immune response to the 1×10¹¹vp 
group, but with a better safety profile [2]. From the data produced in the Phase I and II trials, it 
has been determined that the best dose for the Ad5-nCoV vaccine is 5×10¹⁰ vp.  
1.3. Rationale for the study 
Largely attributable to globalization, without a prophylactic vaccine against SARS-CoV-2, 
COVID-19 will persist as a pandemic threat [2]. The few published clinical trials support the 
need for further researching of the efficacy of receiving vaccines that will protect against SARS-
CoV-2 infections [3].  
This study is a phase IIb clinical trial to collect sufficient safety data to support the use of this 
candidate vaccine in HIV infected individuals.  
Two doses of Ad5-nCoV at 5×1010vp will be administered to adults of 18 years of age and older, 
living with HIV, on stable treatment.  
 

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The Adenovirus type 5 platform has been successfully used by CanSino Biologics in its licensed 
Ebola virus vaccine. Two phase I clinical trials in China and one phase II clinical trial in Sierra 
Leone of Recombinant Ebola Virus Disease Vaccine (Adenovirus Type 5 Vector, rAd5) were 
conducted. The safety data are summarized below.  
 
Between December 2014 and January 2015, a randomized, double-blinded, placebo-controlled, 
phase I clinical trial of single dose rAd5 Ebola vaccine was conducted in Jiangsu Province, 
China, to evaluate the safety, tolerability and immunogenicity in healthy people aged between 18 
to 60 years. The vaccine was well tolerated with an adverse event reported in over 60% of 
participants after their primary immunization, and 71% of participants after the booster dose 6 
months later [6, 7]. Local adverse reactions were pain, induration, and redness, swelling and 
itching. Systemic adverse reactions were fever, headache, fatigue, vomiting, diarrhea, myalgia, 
joint pain, sore throat and cough [6, 7]. Between March and August of 2015, a randomized, 
single center, open-label phase I clinical trial of rAd5 Ebola vaccine was conducted in Zhejiang 
Province, China, to evaluate its safety and immunogenicity in healthy Africans in China [8]. The 
safety results showed that solicited local adverse reactions were pain, swelling, induration and 
redness, mucosal damage, itching and rash at the injection site [8]. From October 2015, a 
randomized, single center, double-blinded, placebo-controlled phase II clinical trial of rAd5 
Ebola vaccine was conducted in Sierra Leone [9], to evaluate its safety and immunogenicity in 
healthy Africans. The safety results showed that solicited local adverse reactions were mainly 
pain [9]. For full study details, please see articles referenced. Most of the adverse reactions were 
mild and self-limited. The above results indicated that the strength and extent of adverse 
reactions are acceptable and the rAd5 Ebola vaccine in healthy adults is tolerable and safe. 
Immunogenicity of the rAd5 Ebola vaccine was demonstrated in all of the reported studies [6-9]. 
Higher antibody titers were demonstrated in participants who had low or absent pre-existing 
antibodies against adenovirus type 5; however, a significant immune response also occurred in 
individuals with pre-existing antibodies. These differences diminished after a booster dose of the 
rAd5 Ebola vaccine at 6 months [6-9]. 
Phase I and Phase II studies of the Adenovirus type 5 platform expressing SARS-CoV-2 spike 
protein have now been completed and demonstrate good safety and immunogenicity. A phase III 
trial to test the efficacy of the Ad5-nCoV vaccine is underway. A phase IIb study in persons 
living with HIV is warranted. 
In its original version, the protocol limited inclusion to "people living with HIV on stable 
treatment and virologically suppressed...".  
Likewise, the design was double-blind versus placebo in a 2:1 ratio.  
The advancement of the national vaccination reduced the possibilities of access to the study 
under such design, for which this protocol amendment was proposed. 

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Volunteers initially included in the study will receive two doses of the vaccine and will continue 
their follow-up as established in the protocol. 
 
2. STUDY OBJECTIVES 
2.1 Primary Objectives 
The primary objectives of the study are related to the safety and immunogenicity of the Ad5-
nCoV in persons living with HIV. 
 
There are four primary safety objectives. 
1. Evaluate the incidence of solicited adverse reactions within 7 days after vaccination.  
2. Evaluate the incidence of unsolicited adverse events within 28 days after vaccination. 
3. Evaluate the HIV viral load 24 and 52 weeks after vaccination. 
4. Evaluate the incidence of serious adverse events (SAE) and medically attended adverse 
events (MAE) within 52 weeks after vaccination in all participants. 
The primary immunogenicity objectives are: 
 Evaluate the seroconversion rate of S-RBD IgG antibody on Day 28, Day 84 and 
Week 24 and Week 52 after vaccination, measured by ELISA. 
 Evaluate the immunogenicity of one versus two doses of the vaccine. 
 
2.2 Secondary Objectives 
2.2.2 Secondary Safety Objective: 
 Evaluate the incidence of a decrease in CD4+ cell count by ≥20% at 24 and 52 
weeks after vaccination. 
 Evaluate changes in the CD4/CD8 ratio at 24 and 52 weeks compared to the basal 
value. 
2.2.3 Secondary Immunogenicity Objectives: 
1. Evaluate the GMT of S-RBD IgG antibody on Day 28, Day 84 and Week 24 and Week 52 
after vaccination, measured by ELISA. 
2. Evaluate the GMI of S-RBD IgG antibody on Day 28, Day 84 and Week 24 and Week 52 
after vaccination, measured by ELISA. 
3. Evaluate the seroconversion rate of pseudo-virus neutralizing antibody on Day 28, Day 84 
and Week 24 and Week 52 after vaccination. 
4. Evaluate the GMT of pseudo-virus neutralizing antibody on Day 28, Day 84 and Week 24 

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and Week 52 after vaccination. 
5. Evaluate the GMI of pseudo-virus neutralizing antibody on Day 28, Day 84 and Week 24 
and Week 52 after vaccination. 
6. Evaluate the positive rate and level of IFN-γ, TNF, IL-4, IL-5, IL-13 stimulated by peptide 
pool of S protein on Day 28, Day 84 and Weeks 24 and Week 52 after vaccination, 
measured by intracellular cytokine staining (ICS) (in a subset of approximately 50 
participants). 
2.2.4 Exploratory Objectives  
1. To evaluate the efficacy of two doses of Ad5-nCoV in preventing virologically confirmed 
(PCR positive) COVID-19 disease occurring 14 days and 28 days to 52 weeks after 
vaccination, regardless of severity.  
2. To evaluate the efficacy of two doses of Ad5-nCoV in preventing virologically (PCR) or 
serologically (four-fold increase in SARS-CoV-2 anti-N IgG from pre-immunization to 
post symptom, defined as Day 21-28 post illness blood test, or pre-symptom and post-
symptom blood test) confirmed COVID-19 disease occurring 14 and 28 days to 52 weeks 
after vaccination, regardless of severity. 
3. To evaluate the efficacy of two doses of Ad5-nCoV in preventing severe COVID-19 
disease caused by SARS-CoV-2 infection from 14 and 28 days to 24 and 52 weeks after 
vaccination. 
Severe disease is defined as: 1) Clinical signs at rest indicative of severe systemic 
illness (respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 
93% on room air at sea level or PaO2/FiO2 < 300 mm Hg), 2) Respiratory 
failure (defined as needing high-flow oxygen, non-invasive ventilation, 
mechanical ventilation or ECMO),  3) Evidence of shock (SBP < 90 mm Hg, DBP 
< 60 mm Hg, or requiring vasopressors), 4) Significant acute renal, hepatic, or 
neurologic dysfunction, 5) Admission to an ICU. 
4. Evaluate the efficacy of two doses of Ad5-nCoV in preventing asymptomatic disease of 
COVID-19 (confirmed by N IgG antibody on week 52 after vaccination). 
5. Evaluate the severity of COVID-19 cases among vaccine recipients (based on WHO or 
FDA criteria) as compared to the control group, to measure antibody-mediated disease 
enhancement (ADE). 
6. Evaluate for any evidence of SARS-CoV-2 virus shedding in COVID-19 cases that 
occurred 28 days to 52 weeks after vaccination (detection of viral nucleic acid every 2 days 
after being confirmed). 
7. Perform genotyping of SARS-CoV-2 virus isolates of COVID-19 cases that occurred 28 
days to 52 weeks after vaccination. 
8. Evaluate incidence of suspected but unconfirmed cases of COVID-19 (either because of 
negative or no tests). 

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3. STUDY DESIGN  
3.1 Summary  
This Phase IIb study is a multi-centre clinical trial; approximately 500 participants 18 years of 
age and older, living with HIV will be enrolled.  
All participants will receive a single dose of the study vaccine (Ad5-nCoV)  on First Injection 
Visit, and a second dose of Ad5-nCoV at Day 56 (Second Injection Visit) and will be followed to 
monitor vaccine candidate safety, immunogenicity (antibody response), and efficacy for a 
duration of 52 weeks. A subset of participants will also have cellular immunity measured after 
receiving the 5×1010 vp Ad5-nCoV vaccine (≥ 4 x1010 vp).   
Candidate Vaccine:   
Ad5-nCoV 
 
 
 
 
Vaccination schedule:  
A double-dose schedule is used for all participants. The First 
dose at the Injection Visit when entering the study and the 
Second dose at Day-56 Visit post baseline vaccination (Second 
Injection Visit). 
Data collection: 
This clinical trial will use a single, designated Electronic Data 
Capture System (EDC) where participant electronic case report 
forms (eCRFs) will be recorded. 
 
Safety Precautions:  
Safety precautions will be outlined in detail in this section, as well 
as Section 7.  
 
Blinding 
3.2 Study Groups  
A total of 500 participants will be enrolled to receive the vaccine. All participants will be 
monitored for solicited adverse events for 7 days, unsolicited adverse events for 28 days, SAEs 
and MAEs for the one year duration of the study, and antibody measurements at baseline, Day 
28, Day 84, week 24, and week 52. A subset of 50 participants will have cellular immunity 
measured at those same intervals. 
This protocol amendment provides for unblinding of participants who were entered into the 
study in the double-blind schedule. For participants who entered the double-blind schedule, the 
visit process will be as follows: 
a) Sites will receive an unblinding list detailing participants who received placebo or study 
vaccine. Participants who received placebo will be invited to continue in the study under the 

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open-label study scheme and should make visits from V1.B (first vaccine) onwards, after signing 
the informed consent, completing visits on day 28 (V2.B), day 56 (second dose) (V3.B), day 84 
(V4.B), week 24 (V5.B) and week 52 (V6.B). In this group of participants already enrolled, no 
antibody dosage collection will be performed at the V1B visit; the V1 values at study entry will 
be taken. The letter B is added to the visits to differentiate this group of participants who must 
reorganize the schedule of visits from the administration of the first dose of CoVID vaccine after 
the unblinding. The procedures for this group are detailed in Table 2. 
b) Participants who, after the unblinding, are found to have received study vaccine at the initial 
visit, will complete the visits established by protocol together with the administration of dose 2 
of the study (day 56) onwards, after signing the informed consent. In this group of participants 
there will be no changes in the nomenclature of the visits. 
For both arms (placebo and study vaccine), efficacy contacts are restarted with the second 
injection visit. 
3.3 Sampling/Study Schedule 
All participants will have at least six planned in-person visits on First Injection Visit and Day 28, 
Day 56 (Second Injection Visit), Day 84, Week 24, and Week 52.  The first visit, the Screening 
visit, will entail reviewing the ICF, completing a medical history of the participant, reviewing 
inclusion and exclusion criteria, collecting samples, performing HIV viral load and CD4/CD8 
counts. At that vist (First Injection Visit), a urine pregnancy test in women of child-bearing 
potential will be performed (local site or laboratory) . The pre-vaccination blood drawn will be 
performed at First Injection Visit to obtain a viral load and a baseline CD4 count (CMH 
laboratory), a baseline SARS-CoV-19 antibody (Nexelis Laboratories), and baseline 
immunogenicity levels. Participants are required to remain at the study site for a minimum of 15 
minutes after receiving the vaccine to monitor for any vaccine-related AE.  
 
Participants will be given access to an e-diary or paper diary card to record solicited AE from 
First Injection Visit- day 7 and unsolicited AE from First Injection Visit-28. Participants will 
review their e-diary or diary card with study staff at their second in-person visit on Day 28.  
A new e-diary or paper diary card to record solicited and unsolicited AEs from Second Injection 
will be provided at Second Injection Visit- Day 56. The data in the completed e-diary or diary 
card will be reviewed and data will be collected at visit on Day 84. 
 
Data collected from e-diaries and diary cards will be uploaded into the participant’s eCRF. 
Further details are outlined in Section 3.7 and 5.1.  
 
All participants will be contacted on a weekly basis by the site (or through an automated message 
(email) with a link to answer the questions on whether or not they had SAE, MAE or COVID-19 
symptoms) to be reminded to report any signs or symptoms of illness to study staff. The 

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reporting and monitoring of any participant illness are consistent with meeting the primary 
efficacy objective. If a participant becomes ill, they will be asked to immediately proceed to the 
site designated by their local study team where they will be assessed and treated as deemed 
appropriate. Participants will also receive a telephone call every 4 weeks to evaluate for the 
incidence of any SAE and MAE.  
 
In-person visits on Screening visit and First Injection Visit, Day 28, Day 84, Week 24 and Week 
52 will also be used for blood sample collection to assess for detailed immunogenicity response. 
Further details are outlined in Section 3.8 and 3.9. 
A subset of approximately 50 participants will have additional immunologic testing performed, 
following the same visit schedule, to evaluate T-cell response to the Ad5-nCoV vaccine.  
 
If a participant demonstrates signs or symptoms of illness, an unplanned in-person visit may 
occur for evaluation and possible treatment. If, for any reason following a participant contact, 
the investigator would like to conduct an in-person visit with a participant, they may do so at 
their discretion.  
3.4 Procedures 
Table 1. In-Person Visits 
Intervention 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
 
Day 0 
(Screeni
ng and 
First 
Injection 
Visit) 
Day 28 
Day 56 
(Secon
d 
Injecti
on 
Visit) 
Day 84 
Week 
24 
Week 
52 
Visit window  
 
 
+/-7 
days 
+/- 7 
days 
+/- 7 
days 
+/-14 
days 
+/-14 
days 
Informed Consent 
 
● 
  
 
 
  
  
Review Consent 
 
● 
● 
● 
● 
● 
● 
Collect Demographic and 
Participant Contact Information 
 
● 
  
 
 
  
  
Blood sample collected for HIV 
viral load and CD4/CD8 counts  
 
● 
 
 
 
● 
● 
Urine Pregnancy test- women of 
childbearing potential 
 
● 
  
● 
 
  
  
Review Inclusion and Exclusion 
criteria 
 
● 
 
● 
 
 
 

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Medical History 
 
● 
  
● 
 
  
  
Check and record prior 
concomitant medication and 
vaccines 
 
● 
  
● 
 
  
  
Check and record intercurrent 
medical conditions 
 
● 
  
 ● 
 
  
  
Check Contraindications to vaccine 
 
● 
  
● 
 
  
  
Pre-injection vital signs  
 
● 
  
● 
 
  
  
Study group and treatment number 
allocation 
 
● 
  
 
 
  
  
Screening conclusion  
 
● 
  
 
 
  
  
Administration of Study Product 
 
● 
  
● 
 
  
  
Safety participant contact (Phone 
call or in-person visit)  
 
 
 
 Every 4 weeks (Day 28, 56 and 84 is 
in person) 
Efficacy participant contact 
(message) (a) 
 
 
 
Weekly from Day 7- week 52 
(visit window: +3 days) 
Safety participant contact: in-
person visit  
 
● 
● 
● 
● 
● 
● 
Paper diary provided to participant  
 
● 
 
● 
 
  
  
E-diary or diary card reviewed with 
participant and data collected and 
uploaded to eCRF 
 
 
● 
 
 
  
  
Immunogenicity participant 
contact: in-person visit 
 
● 
● 
● 
 
● 
● 
Blood Sample Collected for ELISA 
and neutralizing Antibody testing 
(~25mL)  
 
● 
● 
 
● 
● 
● 
Blood Sample Collection for ICS 
testing (~30mL)(b) 
 
● 
● 
 
● 
● 
● 
Study conclusion  
 
  
  
 
 
  
● 
● is used to indicate a study procedure. 
(a):If it is preferable, a phone-call or text instead of email for an efficient participant contact is 
acceptable 
(b): In the subset of approximately 50 participants who will have cellular immunity measured 
Detailed description of study procedures and interventions is outlined in Section 5.1 

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Table 2. Procedures for the group of participants assigned to placebo arm. In-person visit 
Intervention 
 
Visit 1.B 
Visit 
2.B 
Visit 
3.B 
Visit 
4.B 
Visit 
5.B 
Visit 
6.B 
 
Day 0 
(First 
Injection) 
Day 
28 
Day 
56 
(Seco
nd 
Inject
ion) 
Day 
84 
Week 
24 
Week 
52 
Visit window  
 
 
+/-7 
days 
+/- 7 
days 
+/- 7 
days 
+/-14 
days 
+/-14 
days 
Informed Consent 
 
 
  
 
 
  
  
Review Consent 
 
 
● 
● 
● 
● 
● 
Collect Demographic and 
Participant Contact 
Information 
 
 
  
 
 
  
  
Blood sample collected for 
HIV viral load and 
CD4/CD8 counts  
 
 
 
 
 
● 
● 
Urine Pregnancy test- 
women of childbearing 
potential 
 
● 
  
● 
 
  
  
Review Inclusion and 
Exclusion criteria [2] 
 
 
 
● 
 
 
 
Medical History 
 
● 
  
● 
 
  
  
Check and record prior 
concomitant medication 
and vaccines 
 
● 
  
● 
 
  
  
Check and record 
intercurrent medical 
conditions 
 
● 
  
 ● 
 
  
  
Check Contraindications to 
vaccine 
 
● 
  
● 
 
  
  

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Pre-injection vital signs  
 
● 
  
● 
 
  
  
Study group and treatment 
number allocation 
 
 
  
 
 
  
  
Screening conclusion  
 
 
  
 
 
  
  
Administration of Study 
Product 
 
● 
  
● 
 
  
  
Safety participant contact 
(Phone call or in-person 
visit)  
 
 
 
 Every 4 weeks (Day 28, 56 
and 84 is in person) 
Efficacy participant contact 
(message) (a) 
 
 
 
Weekly from Day 7- week 52 
(visit window: +3 days) 
Safety participant contact: 
in-person visit  
 
● 
● 
● 
● 
● 
● 
Paper diary card or e-diary 
provided to participant  
 
● 
 
● 
 
  
  
E-diary or diary card 
reviewed with participant 
and data collected and 
uploaded to eCRF 
 
 
● 
 
● 
  
  
Immunogenicity 
participant contact: in-
person visit 
 
 
● 
● 
 
● 
● 
Blood Sample Collected for 
ELISA and neutralizing 
Antibody testing (~25mL)  
 
 
● 
 
● 
● 
● 
Blood Sample Collection 
for ICS testing (~30mL)(b) 
 
 
● 
 
● 
● 
● 
Study conclusion  
 
  
  
 
 
  
● 
 
 
 

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3.5 Efficacy participant contacts 
Efficacy participant contacts will occur for all participants on a weekly basis. Email or text 
messages will remind participants to report any signs or symptoms of infection to the study staff. 
These participant contacts can also be in-person, by phone, via the Internet or any other suitable 
method. Each contact needs to be recorded in the study electronic case report form.  
Any reported COVID-19 relevant symptoms (e.g. fever, cough, shortness of breath, etc. as per 
WHO case definitions - see below) will trigger laboratory testing for SARS-CoV-2 infection. 
The SARS-CoV-2 nucleic acid test is performed with a throat or nasal swab and repeated within 
3 days later if the result is negative. PCR SARS-CoV-2 tests will be done at Laboratorios 
CMH/Argenomics. Every effort will be made to verify positive PCR tests in a national or 
regional reference laboratory. Participants with a positive nasal/throat PCR will have it repeated 
at the local laboratory every two days in the first week (up to a maximum of 3 PCRs) and then 
weekly until negative. A serum specimen will be collected at the time of illness presentation and 
be repeated between 3 and 4 weeks later for SARS-CoV-2 anti-N IgG antibodies to be performed 
at Nexelis Laboratories for all subjects presented with suspected COVID-19 symptoms, 
regardless of the result of PCR SARS-CoV-2 test.  
 
Figure 1. Procedure algorithm for efficacy contacts 
 
After COVID-19 diagnosis, participants will be referred locally for management, as required. 
Data to determine whether these participants meet criteria for severe COVID-19 or if they 
receive antivirals that could modify the likelihood of severe COVID-19 will be collected. Study 
participant contact for COVID-19 disease is planned to last for at least 12 months.  

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Participants will have contacts via email, text, or phone message on Days 7, 14, 21, 35, 42, 49,, 
63, 70, 77, 91, 98, 105, 112, 119, 126, 133, 140, 147, 154, 161,175, 182, 189, 196, 203, 210, 217, 
224, 231, 238, 245, 252, 259, 266, 273, 280, 287, 294, 301, 308, 315, 322, 329, 336, 343, 350, 
and 357. Participant contacts on Days 56, 84, 112, 140, 196, 224, 252, 280, 308, and 336 will 
have a phone call, in addition to an email or text message. Day 28, 56, 84, 168 (week 24), and 
364 (week 52) will be an in-person visit to accommodate the diary reviews and immunological 
testing.  
The visit window for Efficacy participant contact is +3 days. 
Case definitions for surveillance: 
Suspect case  
Subject with any of the following symptoms (or signs) is reported as suspected case： 
Fever, cough, dyspnoea & difficulty breathing, anosmia/ageusia, chills, myalgia, sore 
throat, prolonged fatigue, diarrhea, nausea, vomiting, headache, congested/runny nose, 
pneumonia, difficulty swallowing, loss of sense of smell and taste, and neurological events.  
 
 
Probable case 
1. A suspect case for whom testing for the COVID-19 virus is inconclusive. 
OR 
2. A suspect case for whom testing could not be performed for any reason. 
Confirmed case 
A suspect case with laboratory confirmation of COVID-19 infection (including PCR positive 
result OR 4 folds or greater increase of anti N IgG at  4 folds or more raise between 
convalescence phase as compared to an acute phase), irrespective of clinical signs and 
symptoms. 
Endpoint case 
Confirmed cases are categorized into primary endpoint cases and secondary endpoint cases 
according to the time of onset after vaccination. 
Primary endpoint: the participant with clinical symptom(s) that occurred not less than Confirmed 
cases with onset date ≥28 days after post- vaccination and the PCR test is positive. 
Secondary endpoint: the participant with clinical symptom(s) that occurred not less than 14 days 
post-vaccination and the PCR test is positive; or 4 folds or greater increase of anti N IgG is 
detected after the occurrence of the clinical symptom(s). 

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Confirmed cases with onset date ≥28 days after vaccination. 
Both primary and secondary endpoint cases need to be reported to the Endpoint Review 
Committee (ERC) for final review. A contact is a person who experienced any one of the 
following exposures during the 2 days before and the 14 days after the onset of symptoms of a 
probable or confirmed case:  
1. Face-to-face contact with a probable or confirmed case within 1 meter and for more 
than 15 minutes; 
2. Direct physical contact with a probable or confirmed case;  
3. Direct care for a patient with probable or confirmed COVID-19 disease without using 
proper personal protective equipment; 
OR 
4. Other situations as indicated by local risk assessments.  
Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 days 
before through the 14 days after the date on which the sample was taken which led to 
confirmation. 
3.6 Immunogenicity In-Person Visits 
Participants will return to the study site on Day 28, Day 84, Week 24, and Week 52 for 
collection of venous blood samples for antibody testing. Approximately 25mL of serum will be 
collected for ELISA and neutralizing antibody testing on Day 28, Day 84, Week 24, and Week 
52.  
In the subset of 50 participants, approximately 30mL of whole blood will be collected on Day 28 
and Day 84, and Week 24 and Week 52 for ELISpot testing and intracellular cytokine staining 
(ICS).  
The visit window for immunogenicity participant contact of Day28 and Day 84 is +/-7 days. 
The visit window for immunogenicity participant contact of Week 24 and Week 52 is +/-14 days. 
Telephone visits and face-to-face visits at the same time point can be combined into one face-to-
face visit. 
4. STUDY POPULATION 
The trial will recruit 500 participants, 18 years of age and older, living with HIV. Recruitment 
should support the generalizability of results, including by important characteristics such as age 
(including elderly). Participants must meet inclusion/exclusion criteria.  

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Participants will be enrolled at 4 study sites in Argentina. Depending on success of participant 
enrolment, as well as the COVID-19 attack rate, this list may be revised to include additional 
sites.  
4.1 Inclusion Criteria  
1. Adults of 18 years of age, and older, with confirmed HIV infection according to criterion 2.  
2. A positive rapid test or ELISA and/or a plasma HIV-1 viral load >1000 copies/ml or rapid test 
or ELISA plus a positive Western Blot test. In patients on antiretroviral treatment, a medical 
history summary or prescription signed and stamped by the treating physician is acceptable. 
Able and willing (in the Investigator's opinion) to comply with all study requirements. 
3. Willing to allow the investigators to discuss the volunteer's medical history with their General 
Practitioner/personal doctor and access all medical records when relevant to study procedures. 
4. Healthy adults, or stable-healthy adults who may have a pre-existing medical condition that 
does not meet any exclusion criteria.  A stable medical condition is defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease during the 3 
months before enrolment [4]. 
5. For subjects of childbearing potential only: Willingness to practice continuous effective 
contraception (see glossary) for 30 days prior to enrolment in the study, for 90 days after 
receiving vaccination during the study, and have a negative pregnancy test on the day(s) of 
screening/ vaccination (First Injection Visit and Second Injection Visit).  
6. Males participating in this study who are involved in heterosexual sexual activity must agree 
to practice adequate contraception (see glossary) and refrain from donating sperm for 90 days 
after receiving the study vaccination.  
7. Agreement to refrain from blood donation during the study. 
8. Provide written informed consent. 
 
 
4.2 Exclusion Criteria  
1. Participation in any other COVID-19 prophylactic drug trials for the duration of the study. 
Note: Participation in COVID-19 treatment trials is allowed in the event of hospitalization 
due to COVID-19. The study team should be informed as soon as possible. 
 
2. Planned receipt of any vaccine (licensed or investigational), other than the study intervention, 
within 14 days before and after study vaccination. 

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3. Prior receipt of an investigational or licensed vaccine likely to impact on the interpretation of 
the trial data (e.g. Adenovirus vectored vaccines, any coronavirus or SARS vaccines). 
4. Administration of immunoglobulins and/or any blood products within the three months prior 
to the planned administration of the vaccine candidate. 
5. Any confirmed or suspected immunosuppressive or immunodeficient state (other than living 
with HIV, on stable treatment, and virologically suppressed for at least 6 months); asplenia; 
recurrent severe infections and chronic use (more than 14 days) of immunosuppressant 
medication within the past 6 months. Topical steroids or short-term (course lasting ≤14 days) 
oral steroids are not an exclusion. 
6. Active opportunistic infections or other AIDS-defining illness in the last six months. 
7. History of allergic disease or reactions likely to be exacerbated by any component of Ad5-
nCoV. 
8. Any history of angioedema. 
9. Any history of anaphylaxis to any vaccine component. 
10. Pregnancy, lactation or willingness/intention to become pregnant within 90 days after 
receiving study vaccine. 
11. Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and 
cervical carcinoma in situ). 
12. History of serious psychiatric condition likely to affect participation in the study. 
13. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history 
of significant bleeding or bruising following IM injections or venepuncture. 
14. Suspected or known current alcohol or drug dependency. 
15. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal 
disease, liver disease, renal disease, endocrine disorder and neurological illness 
(mild/moderate well-controlled comorbidities are allowed). 
16. History of laboratory-confirmed COVID-19. 
17. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) 
or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban). 
18. Any other significant disease, disorder or finding which may significantly increase the risk to 
the volunteer because of participation in the study, affect the ability of the volunteer to 
participate in the study or impair interpretation of the study data. 

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4.3 Recruitment  
Participants will be recruited through invitations to persons in the study center’s participant 
database (who have previously indicated their willingness to be contacted regarding future 
studies) by mail and email, advertising using local print and radio media, social media, e-mail, 
notification through the study sites’ websites, through offices of local physicians, and in 
universities and health care settings. The numbers of persons who express interest in 
participating but are ineligible or declined participation, and reasons, will be recorded in the 
Screening Log. 
5. STUDY PROCEDURES AND INTERVENTIONS 
In-person visits will take place at selected study sites in Argentina, as well as through electronic 
(text message) and telephone calls. These facilities will be authorized by the institution to 
continue to do research related to COVID-19 disease during the pandemic. Scheduling during the 
pandemic will be arranged to minimize any social contact except with study staff. Study staff 
will screen potential participants for respiratory or other COVID-19 symptoms over the phone 
and again upon the participant’s arrival at the study center. Staff will wear medical masks at all 
times when interacting with participants to protect the participant and themselves from the 
potential of virus transmission in an asymptomatic individual, according to local institutional 
policies. These institution-wide precautions are meant to minimize the likelihood of a COVID-19 
outbreak at the clinical trial site putting participants and staff at-risk, and to preserve the integrity 
of the study. These procedures will remain in place as long as the host institutional polices 
require them; study policies will continue to change to align with the host institution’s policies. 
5.1 Study Intervention Descriptions  
All participants will be subject to the following procedures:  
● Informed consent 
The signed informed consent must be obtained before study participation. At each 
subsequent participant contact requiring an intervention (such as collection of a blood 
sample), the participant’s consent will be verified.  
● Check inclusion and exclusion criteria 
All inclusion and exclusion criteria will be checked at the screening in-person visit and will 
be reviewed at the second injection visit. 
● Collect demographic data and participant contact information 
Record demographic data such as date of birth, sex, gender, height, weight and race in the 
participant’s eCRF. Current email addresses and or phone numbers will be collected for each 
participant. It is important to have complete and accurate contact information for each 
participant as the majority of participant contacts will occur electronically. Contact 
information may also be used to remind participants of up-coming in-person visits. 

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● Medical history 
Obtain the participant’s medical history by interview and/or review of the participant’s 
medical records and record any pre-existing conditions or signs and/or symptoms present in 
a participant prior to the first study injection in the eCRF. This will include reviewing any 
health condition that may prevent the participant from enrolling in the study, such as an 
unstable health condition. HIV treatment, clinical status, viral loads and CD4 counts will be 
reviewed. 
● HIV status, viral load, CD4 and CD8 counts 
At Screening visit, HIV status will be verified based on a previous serologic result or 
previous detectable viral load. Viral load samples, and CD4 and CD8 counts will be 
collected at Screening visit, and week 24 and week 52 visits. Screening visit value will be 
used as reference value for comparison with further values.  
● Baseline serology 
Approximately 25 mL of whole blood will be collected from each participant at First 
Injection Visit and separated for serum. The serum will be aliquoted. The first aliquot will be 
used to measure for baseline antibodies against SARS-CoV-2. Presence of pre-existing 
SARS-CoV-2 antibodies found in baseline serum will be used for a stratified 
immunogenicity and efficacy sub-analysis. The second aliquot will be stored as a back-up. In 
participants who entered in the blind version and then were unblinded and vaccinated, 
baseline serology will not be performed again, taking the values of the baseline visit 
performed in the first visit. 
● 
Blood collection for ELISpot and ICS measurement  
In a subset of approximately 50 participants, approximately 30mL of whole blood will be 
collected from participants, in addition to the 25mL being collected for ELISA antibody 
analysis. TNF, IL-4, IL-5, IL-13 will be measured by ICS on first-injection day, Day 28, 
Day 84 and Weeks 24 and 52 after vaccination. PBMC will be shipped on dry ice to Nexelis 
Laboratories (Canada). 
● Check contraindications, warnings and precautions to injection 
Contraindications, warnings and precautions to injection must be checked at the beginning of 
each Injection Visit. 
● Urine Pregnancy Test/Birth Control  
Women of child-bearing age will be asked to perform a urine pregnancy test before each 
Injection Visit. The result of the urine pregnancy test must be negative in order to proceed 
with vaccine administration. In addition, participants who are able to become pregnant or 
could impregnate a partner are required to have used approved contraception least 30 days 
prior to the study vaccination and for 90 days after the study vaccination. 
● Assess pre-injection vital signs (body temperature, blood pressure, pulse rate and 
respiratory rate)  
Body temperature of all participants needs to be measured prior to any study product 
administration. Body temperature may be measured by any method (oral, axillary). If the 

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participant has fever (fever is defined as temperature ≥38.0° C orally or ≥37.8 axillary) on 
the day of injections, the injection visit will be rescheduled within 1 week. 
● Screening conclusion 
Participants will be deemed eligible to participate upon reviewing medical history and 
inclusion and exclusion criteria. This will occur prior to vaccination at First and Second 
Injection Visit.  
● Check and record prior and concomitant medication/vaccines  
Prior medications and concomitant medication/injection must be checked and recorded in the 
eCRF. Prior medications should include any medication taken by the participant within 14 
days prior to screening. Participants will be asked to avoid over-the-counter medications 
such as antipyretics (e.g., acetaminophen) and anti-inflammatory medications (e.g., 
ibuprofen, naproxen) in the 12 hours before study vaccine receipt but will be allowed to take 
these over-the-counter medications as needed to treat fever or other adverse events after 
vaccination. Usage of these over-the-counter medications will be recorded as concomitant 
medications and linked to the adverse event collected as solicited or unsolicited events 
according to the symptom. 
● Check and record intercurrent medical conditions 
Any medical conditions that have arisen are recorded in the eCRF. 
● Treatment number allocation 
The treatment number will be allocated within each step. The number of each administered 
treatment must be recorded in the eCRF. 
● Injection of study vaccine  
After completing all prerequisite procedures prior to the active vaccine injection, one dose of 
the assigned vaccine will be administered IM, in the deltoid muscle, preferable of the non-
dominant arm. If the investigator or delegate determines that the participant’s health on the 
day of administration temporarily precludes administration, the visit will be rescheduled 
within 1 week. There will be a 15-minute wait after each vaccination to monitor for any rare 
anaphylactic reaction. A second injection, of active vaccine Ad5-nCoV, will be administered 
to all participants on Day 56. 
● Safety participant contacts 
Every 4 weeks there will be telephone calls (Weeks 8-52) to continuously collect any SAE 
and MAE data. Participants can report any AE they experience at any time during the study 
period but only SAE and MAE will be entered into the eCRF. Safety participant contacts 
will occur at First Injection Visit (for 15 minutes post-vaccination), Day 28 (to collect the 
diary), Day 56 (Second Injection Visit), Day 84 (to collect the diary), Month 4, 5, 6, 7, 8, 9, 
10, 11, and 12. Safety participant contacts will be a telephone call for Months 2, 3, 4, 5, 7, 8, 
9, 10 and 11, and as an in-person visit on Month 1 (Day 28), Month 2 (Day 56), Month 3 
(Day 84), Month 6 (Week 24), and Month 12 (Week 52).  
● 
E-diary and Diary Cards 

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Participants will be provided with access to an e-diary or a paper diary card and a 
thermometer, and instructions about how to use them. The use of an e-diary instead of a 
paper diary card is dependent on the study site. Participants will be asked to record solicited 
AE for 7 days after receiving the vaccination, and unsolicited AE for 28 days, in their diary. 
The completed e-diary and diary cards will be reviewed, and data collected at the 28-Day 
safety in-person visit.  A new diary will be provided at Day 56 and collected at Day 84. Non 
completion of the e-diary or diary cards will be investigated with the participant through 
telephone call(s) or any other convenient procedure. All data collected from the e-diary and 
diary cards will be uploaded into the eCRF. 
● Efficacy participant contacts 
All participants will have efficacy participant contacts weekly for 52 weeks following 
vaccination. There will be approximately 52 electronic efficacy participant contacts. All 
efficacy participant contacts will be text messages, although other electronic method such as 
by phone, e-email, the Internet is suitable, if preferred. Each participant contact needs to be 
recorded in the study electronic case report form. The purpose of these participant contacts is 
to serve as a reminder to participants to report any symptoms of illness they may be 
experiencing, regardless of severity. Any possible COVID-19 relevant symptoms (e.g., fever, 
cough, shortness of breath, etc., according to WHO case definitions; see Section 3.8) will 
trigger laboratory testing for SARS-CoV-2 infection. 
● Illness participant contact visits (Confirmed or suspected infection during study) 
Participants will be provided detailed instructions regarding the signs and symptoms of 
COVID-19 disease at each participant contact and will be instructed to seek medical 
attention and notify study staff should symptoms occur filling the illness visit form and 
completing the eCRF. The form should be updated and sent and sent when the case meets 
the definition of severe COVID, and when the case resolves. Symptoms of concern include 
cough, fever, diarrhea, prolonged fatigue, respiratory symptoms, pneumonia, difficulty 
swallowing, loss of sense of smell and neurological events. For symptoms of interest, please 
refer to 3.8 efficacy participant contact.  
During the observation period of the study, if any of these symptoms develop in a 
participant, he/she should immediately follow local procedures for care of suspected 
COVID-19 illness and contact the study team. Specimen collection for the study will follow 
the study illness visit algorithm (see Figure 2). The participant’s nasopharyngeal/throat swab 
will be collected and tested for COVID-19 infection in either a local clinical or study site 
laboratory. If negative, the test will be repeated in 3 days. Repeat nasopharyngeal/throat 
swabs will be taken every 2 days until a negative sample is obtained (if possible). A serum 
taken at the time of illness presentation and 2-3 weeks later will be collected for SARS-CoV-
2 anti-N IgG antibodies to be performed in the study central laboratory.  A serum taken at 
the time of illness presentation and 21-28 days later will be collected for SARS-CoV-2 anti-
N IgG antibodies to be performed at Nexelis laboratories for all subjects presented with 
suspected COVID-19 symptom, regardless of the outcome of PCR SARS-CoV-2 test. If a 

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COVID-19 infection is found during the study, a case investigation will be undertaken 
according to locally recommended procedures. Participants who develop COVID-19 
infection post-vaccination will be carefully monitored for vaccine related disease 
enhancement in collaboration with their primary physician who will be encouraged to obtain 
specimens in accordance with the Brighton Collaboration definition (Munoz, 2020).  This 
monitoring may include testing for C-reactive protein (CRP), ferritin, and procalcitonin, 
biomarkers that have been associated with predicting more severe disease outcome in 
infected patients. Repeat nasopharyngeal/throat swabs will be taken every 2 days (by 3 
times) and weekly later until a negative sample is obtained.  Participants who develop 
COVID-19 disease will continue to be followed for other study outcomes by telephone while 
in isolation, and at the study center once recovered and released from isolation by public 
health officials. 
● Immunogenicity in-person visit 
o Blood collection for ELISA Antibody measurement 
o Participants will donateapproximately 25mL of whole blood on First Injection 
Visit, Day 28, Day 84 and Week 24, and Week 52, as described above. Whole 
blood will be separated into serum, and then aliquoted. These in-person visits will 
occur at participants’ local study site. A baseline antibody titer against SARS-
CoV-2 will be established from the blood sample collected on First Injection 
Visit, as outlined in the “baseline serology” description. In addition, these samples 
will also be used to evaluate for additional immunogenicity objectives. Serum 
collected will be analyzed for the seroconversion rate of S-RBD IgG antibody, 
GMT of S-RBD IgG antibody, GMI of S-RBD IgG antibody, seroconversion rate 
of pseudo-virus neutralizing antibody, GMT of pseudo-virus neutralizing 
antibody, and the GMI of pseudo-virus neutralizing antibody at Day 28, Day 84, 
Week 24, and Week 52. The second aliquot will be shipped by the central 
laboratory to Nexelis Laboratories, where it will be stored as a back-up. 
o Blood collection for ELISpot and ICS measurement  
In a subset of approximately 50 participants, approximately 30mL of whole blood 
will be collected from participants on First Injection Visit, Day 28, Day 84 and 
Week 24, and Week 52, as described above. TNF, IL-4, IL-5, IL-13 will be 
measured by ICS on Day 28, Day 84 and Weeks 24 and 52 after vaccination. 
PBMC will be shipped on dry ice to Nexelis Laboratories (Canada). 
● Final serology 
Participants will have an in-person visit on Month 12. Approximately 25 mL of whole blood 
will be collected from each participant and separated for serum into two aliquots. The first 
aliquot will measure antibodies against SARS-CoV-2, at Nexelis laboratories. The second 
aliquot will be shipped by Nexelis laboratories to the Sponsor, where it will be stored as a 
back-up. The one-year antibody levels measured against SARS-CoV-2 will be compared to 

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the participant’s baseline levels to evaluate the exploratory efficacy analysis against 
asymptomatic infection.  
 
The visit window for immunogenicity in-person visits of Day 28 and Day 84 is /-7 days. 
The visit window for immunogenicity in-person visits of Week 24, and Week 52 is +/- 14 days 
5.2 Study conclusion 
Upon study conclusion (52 weeks post-vaccination), the investigators will: 
● 
Review data collected to ensure accuracy and completeness  
● 
Complete the Study Conclusion screen in the eCRF.  
 
6. STUDY PRODUCT AND ADMINISTRATION 
6.1 Description of Study Product  
Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector). This vaccine, Ad5-
nCoV, is a replication-defective recombinant human type 5 adenovirus expressing novel 
coronavirus S protein, which is produced by viral amplification in HEK293SF-3F6 cells, 
purification and formulation with addition of proper excipients. The product is used for 
prevention from infection caused by novel coronavirus. 
Active Ingredients: Replication-defective recombinant human type 5 adenovirus expressing S 
protein of novel coronavirus 
Excipients: 
Mannitol, sucrose, sodium chloride, magnesium chloride, polysorbate 80, 
HEPES, and glycerin 
Packaging:  
The vaccine is contained in a vial. 
Specification:             0.5 mL/vial 
Dosage 
 
5x1010 vp (≥4 x 1010 vp) 
* Explanatory note: The vials contain a volume of 0.5 ml. The indication is to administer this 
amount. The manufacturer of the vaccine has advised that a volume between 0.4 ml and 0.5 ml 
per dose is permitted since it has been calculated that the 0.4 ml extractable volume of each vial 
in the lot involved in this study (Lot NCOV202103006) has met the requirements of the study 
based on good vaccination practices. The vaccines used in this study have passed the quality 
control procedure during the filling process and the fill volume of the vaccines meets the quality 
standards. 
Shelf Life:  
 
Tentatively 24 months 
Storage: 
 
This vaccine should be stored and transported at 2-8℃.  

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Administration: 
Intramuscular injection in the deltoid muscle of the upper arm. 
Schedule: 
A double-dose of active vaccine is planned for all participants. A second 
dose of active vaccine is planned for all participants 56 days after the first 
Injection. 
Manufacturer:  
CanSino Biologics Inc.  
  
 
185 South Ave., TEDA West District, Tianjin, China 
Postal code: 300462 
Tel: 86-022-58213600 
Fax: 86-022-58213677 
Website: www.cansinotech.com 
Developers:                CanSino Biologics Inc. 
Beijing Institute of Biotechnology 
 
Contraindications to the Study Vaccine 
(1) 
Allergic reaction to any component of this vaccine. 
(2) 
Acute illness, acute phase of chronic disease, and fever. 
(3) 
Pregnant and lactating women. 
(4) 
People with thrombocytopenia or hemorrhagic diseases, immune-suppressive therapy or 
immune dysfunction, and uncontrolled seizure disorder and other progressive neurological 
disorders. 
 
Warnings and Precautions 
1. This vaccine is strictly prohibited to be administered by intravascular injection. 
2. Epinephrine and other drugs as well as equipment should be in place when the 
vaccine is used, in case emergency treatment of severe allergic reactions will be 
needed. Those who are immunized with this vaccine should be observed for at 
least 30 minutes at the site. 
3. As with all vaccines, this vaccine may not produce 100% protection in the 
vaccinated population. 
4. The vaccine must be stored in the place not accessible by children. 
5. The vaccine should be shaken before injection. It should not be used under 
following circumstances: presence of foreign objects, cracked vaccine syringe, 
unclear or expired label, or any other abnormal appearance of the vaccine. 
6. No disinfectant in contact with the vaccine when injection. 
 

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6.2. Product Oversight 
Product accountability 
A product accountability log will be maintained by study staff to document the number of vials 
of product received and the disposition of each dose.  
 
Replacement doses 
Replacements will be from the study stock. 
 
Return of Unused Products 
Following verification of product accountability, all empty vials will be destroyed as per site 
policy. At the end of the study, all unused clinical trial vaccine material will be returned to the 
sponsor or disposed of according to the site’s standard operating procedure. 
 
Dosage and administration of study products by the study nurse 
A study nurse at each clinical site will be responsible for the administration of the IM vaccine 
into the patient’s deltoid muscle. Products will be administration according to the prompts in the 
IWRS system. 
 
Contraindications to administration of the investigational product at First Injection Day 
The following events constitute contraindications to administration of the study products at that 
point in time. If any contraindication is present at the time scheduled for injection, the participant 
may be injected at a later date, within the time window specified in the protocol, or withdrawn at 
the discretion of the investigator.  
● Acute disease and/or fever at the time of administration.  
● Fever is defined as temperature ≥38.0°C, taken orally. 
● Participants with a minor illness (such as mild diarrhea, mild upper respiratory infection) 
without fever can be administered the product. 
Contraindications to administration of the study product at Day 56 Second Injection Day 
● Acute disease and/or fever at the time of administration.  
● Suspicion of COVID19 case due to symptoms.   
● Fever (≥ 39.0 °C) lasting at least 72 hs after the first injection. 
● Adverse events related to the study product (severe or serious). 
 
Concomitant medications/products and concomitant administration 
At each participant contact over the phone or in-person, the investigator should question the 
participant about any medication/product taken and injection received by the participant. 
Recording of prior and concomitant medications/products and concomitant administration 

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The following prior and concomitant medications/products/vaccines must be recorded in the 
eCRF if administered during the indicated recording period: 
● All concomitant medications/products, except vitamins and dietary supplements, 
administered from 14 days prior to screening up to 28 days following any dose of study 
product. 
● Any concomitant vaccination administered in the period starting from screening up to 
study end. 
● Prophylactic medication (i.e. medication administered in the absence of ANY symptom 
and in anticipation of a reaction to the injection). E.g. an anti-pyretic is considered to be 
prophylactic when it is given in the absence of fever and any other symptom, to prevent 
fever from occurring.  
● Any concomitant medication/product/vaccine relevant to a SAE* or administered at any 
time during the study period for the treatment of a SAE*, or administered at any time 
during the study for treatment of an adverse event leading to study termination, or 
treatment of an adverse event requiring a medically attended visit. 
*SAEs that are required to be reported per protocol. 
 
Concomitant medications/products/vaccines that may lead to the elimination of a 
participant from according-to-protocol (ATP) analyses 
The use of the following concomitant medications/products/vaccines will not require withdrawal 
of the participant from the study but may determine a participant’s evaluability in the according-
to-protocol (ATP) analysis: 
● Any investigational or non-registered product (drug or vaccine) other than the study 
product(s) used during the study period.  
● A vaccine not foreseen by the study protocol administered during the period starting from 
14 days before injection and ending 14 days after a study vaccine injection. It should be 
noted that in case an emergency mass vaccination for a unforeseen public health threat 
other than COVID-19 is organized by the public health authorities, outside the routine 
immunization program, the time period described above can be reduced if necessary for 
that vaccine provided it is authorized by the regulatory authority and used according to its 
package insert and according to the local governmental recommendations and provided a 
written approval of the Sponsor is obtained. 
● Immunosuppressants or other immune-modifying drugs administered chronically (i.e 
more than 14 days) during the study period (for corticosteroids, this will mean prednisone 
≥ 20 mg/day, or equivalent). Inhaled and topical steroids are allowed. 
● Long-acting immune-modifying drug administered at any time during the study period 
(e.g. infliximab). 

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● Immunoglobulins and/or any blood products administered during the study period. 
Intercurrent medical conditions that may lead to elimination of a participant from ATP 
analyses 
At each participant contact subsequent to the First Injection Visit, it must be verified if the 
participant has experienced or is experiencing any intercurrent medical condition. If it is the case, 
the condition(s) must be recorded in the eCRF. 
Participants may be eliminated from the ATP cohort for immunogenicity if, during the study, 
they incur a condition that has the capability of altering their immune response (e.g. confirmed 
influenza infection) or if they become diagnosed with an immunological disorder. 
7. SAFETY 
A primary objective of this study focuses on the tolerability and safety of receiving two doses of 
5×1010vp Ad5-nCoV vaccine. This will be measured by the incidence of SAE and MAE within 
52 weeks of receiving the vaccine and solicited AE (local injection site reactions and general 
reactions within the seven days following vaccination) and unsolicited AE within 28 days after 
vaccination. 
The investigator or site staff is/are responsible for the detection, documentation and reporting of 
events meeting the criteria and definition of an AE, MAE, or SAE as provided in this protocol. 
Each participant will be instructed to contact the investigator immediately should they manifest 
any signs or symptoms they perceive as serious. 
 
Table 3. Adverse Event Reporting: 
Participants 
30 min 
observation  
First Injection 
Visit- Day 7 
Day 8-28 
Beyond day 29 
until week 52 
All 
Post injection 
AE or SAE 
only 
Solicited AEs and 
unsolicited AEs 
 SAE and MAE 
Any unsolicited 
AE only  
SAE and MAE 
SAE and MAE 
only 
 
7.1 Definitions of an adverse event 
An AE is “an untoward medical occurrence in a clinical investigation subject, temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.” A medical attended AE (MAE) is an AE that requires a visit with the 
healthcare system. A serious AE (SAE) is an untoward medical occurrence that results in death, 
is life-threatening (that is, there was a risk of death at the time of the event), requires 

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hospitalization or prolongation of existing hospitalization occurs, results in disability/incapacity, 
or is a congenital anomaly/birth defect in the offspring of a study subject.  
An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 
medicinal product.  
Examples of an AE include: 
● 
Significant or unexpected worsening or exacerbation of the condition/indication under 
study. 
● 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
● 
New conditions detected or diagnosed after investigational product administration even 
though they may have been present prior to the start of the study. 
● 
Signs, symptoms, or the clinical sequelae of a suspected interaction. 
● 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either investigational 
product or a concurrent medication (overdose per se should not be reported as an 
AE/SAE). 
● 
Signs, symptoms temporally associated with product administration. 
● 
Significant failure of expected pharmacological or biological action. 
● 
Pre- or post-treatment events that occur as a result of protocol-mandated procedures (i.e. 
invasive procedures, modification of participant’s previous therapeutic regimen). 
AEs to be recorded as endpoints (solicited AEs) are described below.  
All other AEs will be recorded as unsolicited AEs. 
Examples of an AE DO NOT include: 
● 
Medical or surgical procedures (e.g. endoscopy, appendectomy); the condition that leads to 
the procedure is an AE/SAE. 
● 
Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination). 
● 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
● 
Pre-existing conditions or signs and/or symptoms present in a participant prior to the first 
study injection. These events will be recorded in the medical history. 
Solicited adverse events 
A solicited adverse event (AE) is a pre-specified outcome that the participant is asked to record 
as present or not, and if present, to apply an intensity rating. Solicited AE are collected daily 
from Days 0 to 7 following administration of the study vaccine. An unsolicited event is one that 

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the participant identifies when asked in a non-leading manner if there have been any changes in 
their health since the last participant contact.  
Solicited AEs (Solicited local (injection-site) and general AEs) occurring during the 7-day 
participant contact period after injection will be recorded.  
Solicited local (injection-site) adverse events 
The following local (injection-site) AEs will be solicited: 
● Pain at injection site 
● Redness at injection site 
● Swelling at injection site 
 
Solicited general adverse events 
The following general AEs will be solicited: 
● Drowsiness 
● Fever 
● Headache 
● Nausea 
● Diarrhea 
● Vomiting 
● Generalized muscle aches 
Note: Temperature will be recorded in the evening. Should additional temperature 
measurements be performed at other times of day, the highest temperature will be recorded in 
the eCRF. 
Definition of a serious adverse event 
An SAE is any untoward medical occurrence that: 
a. Results in death, 
b. Is life-threatening, 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, had it been more severe. 
c. Requires hospitalisation or prolongation of existing hospitalisation,  
Note: In general, hospitalisation signifies that the participant has been admitted at the hospital 
or emergency ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or in an out-patient setting. Complications that occur during 

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hospitalisation are also considered AEs. If a complication prolongs hospitalisation or fulfils 
any other serious criteria, the event will also be considered serious. When in doubt as to 
whether ‘hospitalisation’ occurred or was necessary, the AE should be considered serious. 
Hospitalisation for elective treatment of a pre-existing condition (known or diagnosed prior to 
informed consent signature) that did not worsen from baseline is NOT considered an AE. 
d. Results in disability/incapacity, 
Note: The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. This definition is not intended to include experiences of relatively 
minor medical significance such as uncomplicated headache, nausea, vomiting, diarrhoea, 
influenza like illness, and accidental trauma (e.g. sprained ankle) which may interfere or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. Congenital anomaly/birth defects,  
Note: Medical judgment should be exercised in deciding whether reporting is appropriate in 
other situations, such as important medical events that may not be immediately life-
threatening or result in death or hospitalisation but may jeopardise the participant or may 
require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These should also be considered serious. Examples of such events are 
invasive or malignant cancers, intensive treatment in an emergency room or at home for 
allergic bronchospasm, congenital anomaly/birth defects, blood dyscrasias, or convulsions 
that do not result in hospitalisation. 
Clinical laboratory parameters and other abnormal assessments qualifying as adverse 
events or serious adverse events 
Although routine clinical laboratory monitoring is not a part of this phase IIb trial, a participant 
may undergo laboratory testing for other reasons as part of their normal medical care. In absence 
of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, haematology,) or other 
abnormal assessments (e.g. physical examination findings) that are judged by the investigator to 
be clinically significant will be recorded as AE or SAE if they meet the definition of an AE or 
SAE. Stable and or chronic health conditions that were present at baseline and significantly 
worsen following the start of the study will also be reported as AEs or SAEs. However, abnormal 
laboratory findings associated with existing health condition, unless judged by the investigator as 
more severe than expected for the participant’s condition, will not be reported as AEs or SAEs. 
The investigator will exercise his or her medical and scientific judgment in deciding whether an 
abnormal laboratory finding, or other abnormal assessment is clinically significant. 
7.2 Detection of adverse events  
All participants will be instructed on the recognition of symptoms and signs by the study staff. 
Monitoring for any signs or symptoms of COVID-19 is instrumental in evaluating the efficacy of 

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the candidate vaccine. Participants will be monitored for incidence of local and systemic AE, in 
addition to monitoring for SAE. These participants will be instructed on how to take their 
temperature orally, as well as to record any symptoms in their e-diary or diary card for 28 days 
after receiving the vaccination. A thermometer and access to an e-diary or a paper diary card will 
be provided to record solicited AEs from First Injection Visit-Day 7, and unsolicited AEs from 
First Injection Visit-Day 28. Participants will review their completed e-diary or diary card with 
study staff at their second in-person visit on Day 28. A second e-diary or a paper diary card will 
be provided at Day 56 and will be collected at Day 84. Data collected from e-diaries and diary 
cards will be uploaded into the participant’s eCRF. All participants will be monitored for the 
incidence of SAE and MAE up to 52 weeks after receiving the vaccination, via a phone call 
every 4 weeks. Participants will be instructed to contact study staff by phone (24 hours a day), if 
a MAE or SAE occurs. 
 
AE Type 
  
Solicited AEs/ Unsolicited AEs/MAEs/SAEs 
Method of ‘solicited’ participant contact 
 
E-diary or diary card 
Method of ‘unsolicited’ participant contact 
 
E-diary or diary card** 
Method for reporting SAEs/MAEs 
 
 
SAE report forms 
Method for reporting pregnancies 
 
 
Pregnancy report forms 
 
Time period for detecting and recording adverse events and serious adverse events 
All AEs starting within 28 days following administration of the dose of the study productmust be 
recorded into the appropriate section of the eCRF, irrespective of intensity or whether or not they 
are considered injection related. 
The time period for collecting and recording SAEs and MAEs in all participants will begin at the 
first receipt of study product/comparator and will end on Day 364. 
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from the time 
of the first receipt of study product. SAEs that are related to the investigational product will be 
collected and recorded from the time of the first receipt of study product/comparator until the 
participant is discharged from the study. 
In addition to the above-mentioned reporting requirements and in order to fulfill international 
reporting obligations, SAEs that are related to study participation (i.e. protocol-mandated 
procedures, invasive tests, a change from existing therapy) will be collected and recorded from 
the time the participant consents to participate in the study until she/he is discharged from the 
study. 

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Post-Study adverse events and serious adverse events 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE reporting 
period. Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the investigator learns of any SAE at any time after a participant has been 
discharged from the study, and he/she considers the event reasonably related to the 
investigational product, the investigator will promptly notify the Study Contact for Reporting 
SAEs. 
Evaluation of adverse events and serious adverse events 
Active questioning to detect adverse events and serious adverse events 
As a consistent method of collecting AEs, the participants should be asked a non-leading 
question such as: 
‘Have you acted differently or felt different in any way since receiving the product or since the 
last visit?’ 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(e.g. hospital progress notes, laboratory and diagnostics reports) relative to the event. The 
investigator will then record all relevant information regarding an AE/SAE in the eCRF.  
The investigator will attempt to establish a diagnosis pertaining to the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis should be documented 
as the AE/SAE and not the individual signs/symptoms. 
 
Assessment of adverse events 
Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
The maximum intensity of local injection site redness/swelling will be scored as follows: 
0: ≤ 20 mm 
1: > 20 - ≤ 50 mm 
2: > 50 - ≤ 100 mm 
3: > 100 mm 
 
The grade of fever will be scored as follows (oral temperatures*): 
1: ≥ 38.0°C (100.4°F) - ≤ 38.5°C (101.3°F) 
2: > 38.5°C (101.3°F) - ≤ 39.0°C (102.2°F) 
3: > 39.0°C (102.2°F) - ≤ 40.0°C (104°F) 
4: > 40.0°C (104°F) 
*oral temperature=axillary temperature+0.2°C 

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The investigator will assess the maximum intensity that occurred over the duration of the event 
for all unsolicited AEs (including SAEs) recorded during the study. The assessment will be 
based on the investigator’s clinical judgment. 
The intensity should be assigned to one of the following categories: 
● Grade 1 (mild) = An AE which is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
● Grade 2 (moderate) = An AE which is sufficiently discomforting to interfere with normal 
everyday activities. 
● Grade 3 (severe) = An AE which prevents normal, everyday activities 
● Grade 4= An adverse event that is potentially life threatening. 
● Grade 5=An AE which results in death. 
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 3 is a 
category used for rating the intensity of an event; and both AEs and SAEs can be assessed as 
Grade 3. An event is defined as ‘serious’ when it meets one of the predefined outcomes. 
Assessment of causality 
The investigator is obligated to assess the relationship between investigational product and the 
occurrence of each AE/SAE. The investigator will use clinical judgment to determine the 
relationship. Alternative plausible causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
investigational product will be considered and investigated. The investigator will also consult the 
IB and/or PI to determine his/her assessment. 
There may be situations when a SAE has occurred, but the investigator has minimal information 
to include in the initial SAE report. However, it is very important that the investigator always 
assesses causality for every event prior to submission of the SAE report. The investigator may 
change his/her opinion of causality in light of participant contact information and update the 
SAE information accordingly. The causality assessment is one of the criteria used when 
determining regulatory reporting requirements. 
In case of concomitant administration of multiple products, it may not be possible to determine 
the causal relationship of general AEs to the individual products administered. The investigator 
should, therefore, assess whether the AE could be causally related to injection rather than to the 
individual products. 
All solicited local (injection site) reactions will be considered causally related to injection. 
Causality of all other AEs should be assessed by the investigator using the following question: 
Is there a reasonable possibility that the AE may have been caused by the investigational 
product? 

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YES: There is a reasonable possibility that the product(s) contributed to the AE. 
NO: There is no reasonable possibility that the AE is causally related to the administration of the 
study product(s). There are other, more likely causes and administration of the study product(s) 
is not suspected to have contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’, additional examinations/tests will be 
performed by the investigator in order to determine ALL possible contributing factors for each 
SAE. 
Possible contributing factors include: 
● 
Medical history. 
● 
Other medication. 
● 
Protocol-required procedure. 
● 
Other procedure not required by the protocol. 
● 
Lack of efficacy of the product, if applicable. 
● 
Erroneous administration. 
● 
Other cause (specify). 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) recorded during 
the study as: 
● 
Recovered/resolved. 
● 
Recovering/resolving. 
● 
Not recovered/not resolved. 
● 
Recovered with sequelae/resolved with sequelae. 
● 
Fatal (SAEs only). 
 
Medically attended AEs (MAEs) 
For each solicited and unsolicited symptom the participant experiences, the participant will be 
asked if they received medical attention defined as hospitalisation, or an otherwise unscheduled 
visit to or from medical personnel for any reason, including emergency room visits. This 
information will be recorded in the in the eCRF.  
Prompt reporting of SAE, SUSAR and other events to IDMC, Research Ethics Board 
(IRB) 
SAEs will be reported promptly to the Independent Data Monitoring Committee and IRB within 
the timeframes described in this protocol once the investigator determines that the event meets 
the protocol definition of a SAE. SAEs will be collected throughout the study. If anSAE is 
confirmed as aSUSAR, then the sponsor will report it to the IDMC. 

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TABLE 4. TIMEFRAMES FOR SUBMITTING SAES TO RESEARCH ETHICS BOARD AND STUDY 
FARMACOVIGILANCE UNIT 
Type of 
Event 
Initial Reports 
Participant contact of Relevant 
Information on a Previous Report 
 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* 
SAE report 
24 hours* 
SAE report 
* Timeframe allowed after receipt or awareness of the information. 
 
Contact information for reporting serious adverse events and Back-up Study Contact for 
Reporting SAEs 
24/24 hour and 7/7-day availability: 
Email: fvcansino@huesped.org.ar; uam@huesped.org.ar 
Details and contact information will be described in a separate Pharmacovigilance Agreement. 
Completion and transmission of SAE reports  
Once an investigator becomes aware that a SAE has occurred in a study participant, the 
investigator (or designate) must complete the information in the SAE report as thoroughly as 
possible with all available details of the event, WITHIN 24 HOURS. Even if the investigator 
does not have all information regarding a SAE, the report should still be completed within 24 
hours. Once additional relevant information is received, the report should be updated WITHIN 
24 HOURS. The investigator will always provide an assessment of causality at the time of the 
initial report. 
Updating of SAE information after freezing of the participant’s eCRF 
When additional SAE information is received after freezing of the participant’s eCRF, new or 
updated information should be recorded on a paper report, with all changes signed and dated by 
the investigator. The updated report is provided to the IRB. 
Regulatory reporting requirements for serious adverse events 
The investigator will promptly report all SAEs to the in accordance with the procedures detailed 
in this protocol. Fundación Huésped as the clinical trial sponsor, has a legal responsibility to 
promptly notify the appropriate health agency about the safety of a product under clinical 
investigation. Prompt notification of SAEs by the investigator to the Study Contact for Reporting 
SAEs is essential so that legal obligations and ethical responsibilities towards the safety of other 

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participants are met. The purpose of the report is to fulfill specific regulatory and GCP 
requirements, regarding the product under investigation. All of these notifications will occur 
within 24 hours of the Investigator becoming aware of the SAE.  
7.3 Participant contact of adverse events and serious adverse events 
Participant contacts during the study 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
and provide additional relevant information on the participant’s condition to the IRB. 
All SAEs documented at a previous visit/contact and designated as not recovered/not resolved or 
recovering/resolving will be reviewed at subsequent visits/contacts until the end of the study. 
With the exception of MAEs, all AEs documented at a previous visit/contact and designated as 
not recovered/not resolved or recovering/resolving will be reviewed at subsequent visits/contacts 
until 28 days after vaccination. 
Participant contact after the participant is discharged from the study 
The investigator will follow participants: 
● With SAEs, or participants withdrawn from the study as a result of an AE, until the event 
has resolved, subsided, stabilized, disappeared, or until the event is otherwise explained, 
or the participant is lost to participant contact, defined as four attempts to contact by 
phone/email at different times of the day have been unsuccessful and a letter has been 
sent to the address with no reply. 
● With MAE until the end of the study or the participants are lost to participant contact. 
● With other non-serious AEs, until Day 28 after injection or they are lost to participant 
contact. 
If the investigator receives additional relevant information on a previously reported SAE, he/she 
will provide this information to the IRB using a paper SAE and/or pregnancy report as 
applicable. 
The manufacturer of the investigational product may request that the investigator performs or 
arranges the conduct of additional clinical examinations/tests and/or evaluations to elucidate as 
fully as possible the nature and/or causality of the AE or SAE. The investigator is obliged to 
assist. If a participant dies during participation in the study or during a recognized participant 
contact period, the IRB will be provided with any available post-mortem findings, including 
histopathology. 

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7.4 Treatment of adverse events 
Treatment of any AE is at the sole discretion of the investigator and according to current good 
medical practice. Any medications administered for the treatment of an AE should be recorded in 
the participant’s eCRF. 
 
Participant card 
Study participants must be provided with the telephone number of the main contact for 
information about the clinical trial. Participants must be instructed to keep participant cards in 
their possession at all times. 
 
The investigator (or designate) must therefore provide a “participant card” to each participant. In 
an emergency situation this card serves to inform the responsible attending physician that the 
participant is in a clinical study and that relevant information may be obtained by contacting the 
investigator. 
8. PARTICIPANT COMPLETION AND WITHDRAWAL 
8.1 Participant completion 
A participant who returns for the concluding visit/is available for the concluding contact foreseen 
in the protocol is considered to have completed the study. 
8.2 Participant withdrawal 
Participants who are withdrawn because of SAEs/AEs must be clearly distinguished from 
participants who are withdrawn for other reasons. Investigators will follow participants who are 
withdrawn as result of a SAE/AE until resolution of the event. Withdrawals will not be replaced, 
unless the withdrawal is prior to the first dose of study vaccine. 
 
Participant withdrawal from the study 
From an analysis perspective, a ‘withdrawal’ from the study refers to any participant who did not 
come back for the concluding visit/was not available for the concluding contact foreseen in the 
protocol. 
All data collected until the date of withdrawal/last contact of the participant will be used for the 
analysis. 
A participant is considered a ‘withdrawal’ from the study when no study procedure has occurred, 
no participant contact has been performed and no further information has been collected for this 
participant from the date of withdrawal/last contact. 

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Investigators will make an attempt to contact those participants who do not return for scheduled 
visits or participant contact. 
Information relative to the withdrawal will be documented in the eCRF. The investigator will 
document whether the decision to withdraw a participant from the study was made by the 
participant, or by the investigator, as well as which of the following possible reasons was 
responsible for withdrawal: 
● 
SAE 
● 
Non-serious AE 
● 
Protocol violation (specify) 
● 
Consent withdrawal, not due to an AE* 
● 
Moved from the study area. 
● 
Lost to participant contact. 
● 
Other (specify). 
*In case a participant is withdrawn from the study because he/she has withdrawn 
consent, the investigator will document the reason for withdrawal of consent, if specified 
by the participant, in the eCRF. 
Participants who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigators will follow 
participants who are withdrawn from the study as result of a SAE/AE until resolution of the 
event. 
Participant withdrawal from investigational product 
A ‘withdrawal’ from the investigational product refers to any participant who does not receive 
the complete treatment, i.e. when no further planned dose is administered from the date of 
withdrawal. A participant withdrawn from the investigational product may not necessarily be 
withdrawn from the study as further study procedures or participant contact may be performed 
(safety or immunogenicity) if planned in the study protocol. 
Information relative to premature discontinuation of the investigational product will be 
documented on the Product Administration screen of the eCRF. The investigator will document 
whether the decision to discontinue further injection/treatment was made by the participant, or by 
the investigator, as well as which of the following possible reasons was responsible for 
withdrawal: 
● 
SAE 
● 
Non-serious AE 
● 
Other (specify) 

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9. OUTCOME MEASURES AND STATISTICAL METHODS  
 9.1 Sample Size Estimation  
Since this is an open, non-comparative study that seeks to observe the impact of vaccination on 
the evolution of HIV disease, a sample size defined by statistical criteria is not established. 
 
9.2 Study Population and Analysis Sets 
9.2.1 Study Population 
Intent-to-Treat Cohort 
The intent-to-treat cohort consists of all participants who receive at least one study injection, 
regardless of their protocol adherence and continued participation in the study. Participants will 
be analyzed according to their randomized treatment. Participants who withdraw from the study 
will be included up to the date of their study withdrawal. 
Per-protocol Analysis Cohort 
The per-protocol analysis cohort for safety includes subjects in the intent-to-treat who receive the 
correct treatment, the correct number of doses, and who do not have a major protocol deviation. 
Detailed definition of this analysis set including definition of major protocol deviations will be 
described in the Statistical Analysis Plan. The per-protocol analysis cohort for immunogenicity 
includes subjects in the per-protocol analysis cohort for safety whose samples were drawn inside 
of protocol specified time windows. 
9.3 Statistical Analysis 
This purpose of this section is to describe various planned analyses in this study. Details of 
statistical methods will be included in the Statistical Analysis Plan, which will be finalized prior 
to the first interim analysis. 
9.3.1 Demographics and Baseline Characteristics 
Demographic and baseline characteristics will be summarized overall and then by treatment 
group using appropriate descriptive statistics. Continuous data will be summarized using the 
number of observations, mean, standard deviation, median, minimum and maximum. Categorical 
data will be summarized using frequency counts and percentages. 95% confidence intervals will 
be reported, but no statistical hypothesis testing will be conducted. Results will be presented for 
all participants. 
9.3.2 Efficacy Analysis  
Due to limited sample size, no formal efficacy hypothesis will be tested. A listing of baseline 
characteristics, treatment group and outcome for virologically confirmed (PCR positive) 
serologically confirmed COVID-19 cases will be produced. An exploratory efficacy analysis of 

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Ad5-nCoV in preventing asymptomatic disease of COVID-19 will also be conducted at the end 
of the study. 
9.3.3 Safety Analysis 
Primary Safety Endpoint: 
● The incidence of solicited adverse reactions within 7 days after vaccination.  
● The incidence of unsolicited adverse events within 28 days after vaccination. 
● The incidence of detectable viral load 24 and 52 weeks after vaccination 
● The incidence of serious adverse events (SAE) and medically attended adverse events 
(MAE) within 52 weeks after vaccination in all participants. 
 
Secondary Safety Objective Endpoints  
● The incidence of a decrease in CD4+ cell count by ≥20% at 24 and 52 weeks after 
vaccination 
● The delta in the CD4/CD8 rate compared to the basal value. 
 
All SAEs will be listed and summarized by groups.  
For each participant, the individual local events will be aggregated into a combined event 
“Local”, which is the maximum severity of the individual local events. For each participant, the 
individual general events will be aggregated into a combined event “General”, which is the 
maximum severity of the individual general events. An aggregate event “Any” will be defined as 
the maximal severity of the combined events “Local” and “General”. In addition to being graded 
for severity as mild, moderate or severe, the severity of all events will be graded as "Any", which 
will include mild, moderate or severe events, and "Significant" which will include moderate or 
severe events. 
All statistical tests on safety performed will be 2-sided with Type I error of 5%. Missing values 
will not be included in the safety analyses, and there will be no imputation of missing values. No 
adjustments will be made for multiple comparisons. 
For the analysis of proportions, binomial point estimates and exact binomial confidence intervals 
will be calculated. 
Fisher’s Exact Test will be used to assess differences in rates of adverse events between 
treatment and control groups.  
In addition, all safety data will be analysed descriptively, including unsolicited events collected 
through the end of the observation period.  
The Safety analysis will be performed based on the intent-to-treat cohort and per-protocol cohort. 

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9.3.4 Immunogenicity Analysis 
Primary Immunogenicity Endpoints: 
● Evaluate the seroconversion rate of S-RBD IgG antibody on Day 28, Day 84, and Week 
24 and Week 52 after vaccination, measured by ELISA. 
● Evaluate the above-mentioned parameters comparing one versus two Ad5-nCoV doses. 
Secondary Immunogenicity Endpoints: 
● GMT of S-RBD IgG antibody on Day 28, Day 84 and Week 24 and Week 52 after 
vaccination, measured by ELISA. 
● GMI of S-RBD IgG antibody on Day 28, Day 84 and Week 24 and Week 52 after 
vaccination, measured by ELISA. 
● Seroconversion rate of pseudo-virus neutralizing antibody on Day 28, Day 84 and Week 
24 and Week 52 after vaccination. 
● GMT of pseudo-virus neutralizing antibody on Day 28, Day 84 and Week 24 and Week 52 
after vaccination. 
● GMI of pseudo-virus neutralizing antibody on Day 28, Day 84 and Week 24 and Week 52 
after vaccination. 
● Positive rate and level of IL-2, IL-4, IL-13, and IFN-γ stimulated by peptide pool of S 
protein on days 28, Day 84 and Week 24 and Week 52 after vaccination, measured by 
intracellular cytokine staining (ICS). 
 
Geometric mean antibody titers (GMTs) and GMI’s and their two side 95% confidence intervals 
will be calculated by group. Analyses will be performed on the logarithmically (base 10) 
transformed values. Individual titers below the detection limit will be set to half the limit. 
For the analysis of proportions, binomial point estimates and exact binomial confidence intervals 
will be calculated for each group. Rates will be compared between groups using Fisher’s exact 
tests, and geometric means will be compared using t-tests. 
All statistical tests performed for immunogenicity will be 2-sided with Type I error rate of 5%.  
Missing values will not be included in the immunogenicity analyses, and there will be no 
imputation of missing values. No adjustments will be made for multiple comparisons. 
Both per-protocol and intent-to-treat immunogenicity analyses will be carried out. The per-
protocol immunogenicity analysis set will exclude subjects whose samples were drawn outside 
of protocol specified time windows.  
9.3.5 Analysis of exploratory endpoints 
Exploratory endpoints 

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● Efficacy of two doses of Ad5-nCoV in preventing symptomatic disease of COVID-19 
(confirmed by PCR) occurring 14 and 28 days to 52 weeks after vaccination, regardless 
of severity. 
● Efficacy of  two doses of Ad5-nCoV  in preventing virologically (PCR) or serologically 
(four-fold increase in SARS-CoV-2 anti-N IgG from pre-immunization to post symptom, 
defined as Day 21-28 post illness blood test, or pre-symptom to post-symptom blood test) 
confirmed COVID-19 disease occurring 14 and 28 days to 52 weeks after vaccination, 
regardless of severity. 
● Efficacy of two doses of Ad5-nCoV in preventing severe COVID-19 disease caused by 
SARS-CoV-2 infection from 14 and 28 days to 24 and 52 weeks after vaccination. 
● Efficacy of two doses of Ad5-nCoV in preventing asymptomatic disease of COVID-19 
(confirmed by N IgG antibody on week 52 after vaccination). 
● Severity of COVID-19 cases among vaccine recipients (based on WHO or FDA criteria) 
as compared to the control group, to measure antibody-mediated disease enhancement 
(ADE). 
● SARS-CoV-2 virus shedding in COVID-19 cases that occurred 28 days to 52 weeks after 
vaccination (detection of viral nucleic acid every 2 days after being confirmed). 
● Genotype of SARS-CoV-2 virus isolates of COVID-19 cases that occurred 28 days to 52 
weeks after vaccination. 
● Suspected but unconfirmed cases of COVID-19 (either because of negative or no tests). 
● Evaluate incidence of suspected but unconfirmed cases of COVID-19 (either because of 
negative or no tests). 
 
Analysis of endpoints will be descriptive. PCR confirmed positive subjects will be classified as 
having severe or non-severe disease. Severity of disease, SARS-CoV-2 virus shedding and 
Genotypes SARS-CoV-2 virus isolates will be listed by subject and date, along with 
demographic data, including the study centre. Suspected but unconfirmed cases and 
asymptomatic cases will also be listed. 
 
10. DATA MANAGEMENT 
10.1 General Requirements 
The data management of this clinical trial will follow the CDISC standard. A designated person 
(Central Data Manager) will be responsible for the data management of global clinical trial and 
develop a core data management plan approved by the global PI and the sponsor. The local PI of 
each participating country along with the Sponsor will identify a local CRO to monitor data entry 
and ensure compliance with the CDISC standard. 

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10.2 Electronic Data Capture System 
This clinical trial will use a single, designated Electronic Data Capture System (EDC) in all 
participating countries. The local PI of each country must ensure that its research team is well 
trained in EDC system operation skills. 
11. STUDY SUSPENSION CRITERIA AND SAFETY MONITORING 
The study in its entirety may be terminated prematurely with reasonable justification by Study 
Steering Committee, National Regulatory Authority (ANMAT), or the Ethics Committee with 
oversight responsibilities at any time, and/or individual participants may terminate their 
participation prematurely, or have their participation be terminated by the Investigator. 
An Independent Data Monitoring Committee (IDMC) will be established to review the safety 
data of every participant with a GRADE 4 adverse event. Meetings will also be held should a 
participant have an adverse event meeting a “holding rule”. The safety review will be conducted 
using blinded data. The efficacy review will use unblinded data, but interim reports will not 
disclose the data at least that IDMC suggest changes in the protocol due to efficacy concerns. 
11.1 Study Suspension Criteria 
If a suspension criterion is activated, the study will be put on hold, and further injections will not 
be administered until a safety review has been conducted. Should a suspension criterion be 
activated, the local PI will inform the global PI, Sponsors, and NRA within 24 hours.  
Suspension criteria include:  
● More than 15% of participants experience a Grade 3 AE beginning within 3 days after 
study injection (day of injection and 2 subsequent days) and persisting at Grade ≥ 3 on 
three consecutive days depending upon symptom severity and kinetics. 
● A suspected, unexpected serious adverse reaction (SUSAR) occurs that is life-threatening 
or results in death. 
● The IDMC assessed the potential safety risks in clinical studies. 
● The IDMC assessed that the vaccine candidate might be ineffective. 
11.2 Study Early Termination Criteria 
● Required by the sponsor, or 
● Required by the regulatory authority, or 
● Required by an institutional review board (IRB) 
11.3 Process of Suspension of Injection and/ or Study Modification 
In the event that a safety signal is observed, the IDMC might decide to cancel injection of all 
groups (early termination of study) or selected groups. 
In this case, for impacted groups: 

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● Participants who are already injected will continue all visits as planned. 
● 
Participants who signed an informed consent but have not received any study product 
will be informed that their study participation will be stopped. 
Details of the IDMC functioning are described in the IDMC Charter.  
12. STUDY GOVERNANCE 
The study will be managed by Fundación Huésped. It is Fundación Huésped responsibility to 
oversee all study site activities. There will also be a designated IDMC to continuously monitor 
and review data from safety and efficacy trial. 
12.1 Study Steering Committee 
A Study Steering Committee (SC) will be established by the sponsor as the management 
decision-making body for this clinical trial. The SC will provide guidance to Fundación Huésped 
who will be responsible to ensure that the conduct of the trial in each site is harmonized with 
respect to important aspects such as data collection, laboratory tests, and implementation of 
vaccination. Approval, revision, adaptive adjustment of the clinical trial protocol, and major 
issues such as suspension and termination of clinical trials will all be decided by SC. 
The composition of SC is as follows: 
● Representatives from the sponsor 
● PI and co-Global co-PI 
● Central Safety Physician 
● Central Statistician 
The main responsibilities of PI and Global co-PI are: 
● Assisting the sponsor to formulate the clinical trial protocol. 
● In the course of clinical trials, coordinating the progress of each clinical trial site, and 
making recommendations for adaptive adjustment according to changes in circumstances 
(e.g., COVID-19 attack rate). 
● When necessary, working with country PI to resolve issues that arise in the course of 
clinical trials. 
● Preparing study reports for clinical trial. 
● Working with the Study Statistician to finalize the Statistical Analysis Plan (SAP) 
● Drafting local implementation documents and informed consent form (ICF) based on the 
clinical trial protocol and ICF. 

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● Submission of protocol, ICF, and other study documentation to the local IRB. 
● Conducting clinical trials based on the approved implementation protocol. 
● Solving the problems that occurred during the clinical trial. 
● Preparing study reports for the sub-center clinical trial. 
 
12.2 Endpoint Review Committee 
The Endpoint Review Committee (ERC) will be blinded to the treatment assignments. Each 
endpoint case will be reviewed independently by two ERC members to confirm endpoint and 
severity; if their adjudications conflict, the endpoint will also be reviewed by a third member and 
the endpoint will be adjudicated by the majority vote. Members of the ERC will be appointed by 
the Study Steering Committee. Each positive laboratory result will be reviewed by the ERC. A 
detailed outline of ERC regulations and endpoint case criteria, in addition to the criteria defined 
below, will be available in the ERC charter.  
 
Endpoints cases are defined by any of the following events:  
1. A participant has an illness visit and virological confirmation (positive PCR test). PCR 
SARS-CoV-2 tests are permitted to be carried out at local study sites. Every effort will be 
made to verify positive PCR tests in a central reference laboratory. 
2. A participant has an illness visit and serological confirmation of SARS-CoV-2. A 
positive serology test is defined by a four-fold rise or greater to N antibody titers in 
association with the illness. 
3. A participant has illness visit and both virological and serological confirmation.  
4. A participant who does not present with any symptoms (does not have any illness visits) 
but demonstrates seroconversion to the N antigen between the Injection and Week 52 
visits.  
12.3 Independent Data Monitoring Committee 
The sponsor will establish an Independent Data Monitoring Committee (IDMC) consisting of at 
least 3 members to review global clinical trial safety and efficacy data. The IDMC core members 
will include an independent safety physician, clinical trial experts, an independent expert 
physician, infectious disease clinicians, biostatisticians, and epidemiologists who are not 
otherwise involved in the conduct of the project. 
IDMC’s main responsibilities are: 
● Reviewing the reported safety data in the participants after vaccination. 
● Assessing the safety, if necessary, in the context of efficacy, of the investigational vaccine 
to safeguard the interests of trial participants. 

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● Conducting interim analysis and terminate the trial early (for benefit or futility) when 
sufficient evidence of efficacy is obtained. 
● Monitoring the overall conduct of the clinical trial to protect its validity and credibility. 
13. ETHICAL AND REGULATORY CONSIDERATIONS 
This study will be conducted in accordance with all regulatory requirements. The trial will be 
conducted in accordance with the latest version of the Declaration of Helsinki, GCP, ICH 
regulatory guidelines, and requirements regarding ethical committee review, informed consent, 
and other statutes and regulations regarding the protection of the rights and wellbeing of 
participants in the study. 
Each enrolment site and local investigator will be responsible for submitting this protocol, the 
informed consent document, and all recruiting materials to their local independent Research 
Ethics Board (IRB) for review and approval.  
No changes will be made to the protocol without IRB approval, except where necessary to 
eliminate apparent immediate hazards to participants.  
Participants will be able to withdraw their consents to participate at any time without giving a 
reason and with assurance that their care will not be affected in any way. The investigators may 
withdraw a participant if, in the investigator’s clinical judgment, it is in the best interest of the 
participant or if the participant is unable to comply with study requirements. 
13.1 Benefits/Potential Risks 
A complete description of the potential risks and benefits can be found in the informed consent 
document and Investigator Brochure [10]. 
13.2 Informed Consent Process and Documentation 
The investigator or designate person will be responsible for presenting a full description of the 
research project including risks/benefits, and how personal health information may be used and 
disclosed in research. A written informed consent/authorization will then be obtained from the 
participant prior to the screening procedures and injection. The principal investigator or 
designate will also be responsible for maintaining up-to-date records of the consent forms and 
providing a copy to the participant.  
Participants will be encouraged and will have ample opportunity to have their questions 
answered before and after consenting to participate.  
13.3 Modification of the Protocol 
No modifications of the protocol may be made by study personnel without consultation the 
principal investigator. Any protocol amendment will be submitted to the appropriate local 
regulatory authority and to the Research Ethics Board(s) for approval. 

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13.4 Interruption of the Trial 
Study suspension and early termination are described in Section 12.  
13.5 Confidentiality of Data and Access to Participant Records 
Confidentiality will be maintained within legal limits in the review of medical records and 
consent forms, which may contain the identity of the participant. Such records will be coded only 
with the participant’s initials and study number. 
13.6 Monitoring 
The sponsor will assign a professional staff to monitor the clinical trial, following the 
implementation protocol. The sponsor has a clinical trial quality management system and 
experience in the management of vaccine clinical trials. Monitors will follow the research sites’ 
SOP for clinical trial monitoring. 
The study monitoring will start once the first participant has been enrolled in each site, during 
the study at appropriate intervals, and after the last participant has completed the study. The 
monitoring visit schedule will be determined by the sponsor and principal investigator based on 
the monitoring plan, the frequency of enrolments and participant contact visits. A monitor visit 
tracking form and report will be required for each monitoring visit.  
13.7 Auditing 
Audits or inspections may be made by the IRB to ensure that the study has been conducted in 
accordance with the protocol, FDA, ICH/GCP, and the ANMAT. Inspections may also be 
performed by a Country’s regulatory health authority at any point in the study. 
13.8 Archiving 
The investigators will retain all generated documents and study records on site, including 
informed consent forms and copies of case report forms for 10 years after completion of the 
study. 
13.9 Stipends for Participation 
Participants will be provided a stipend according to local practice to compensate for their time 
and travel required for each visit to the study site. 
13.10 Adverse Event Compensation and Insurance 
In the occurrence of an adverse event, the participant will be evaluated and treated by the 
investigators in accordance with local regulations. An insurance contract will be issued by the 
sponsor before starting the trial. 

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13.11 Publication Policy 
Study result manuscripts will be prepared by the Principal Investigator and Global co-PI, 
reviewed by all investigators and the study sponsor, and submitted to peer-reviewed journals and 
scientific meetings within 24 months of the last participant contact.  
14. ADMINISTRATIVE MATTERS 
To comply with ICH GCP administrative obligations relating to data collection, monitoring, 
archiving data, audits, confidentiality and publications must be fulfilled. 
14.1 Data Entry Instructions 
Clinical data management will be performed at each enrollment site, following SOP standards 
and data cleaning procedures and under the supervision of the appointed Data Manager. Data 
entry will be performed by each of the study sites. 
Completed eCRFs are reviewed by the external Monitor at the study site. When omissions or 
inconsistencies are detected by eCRF review, clarification or correction of the eCRF may be 
necessary, following approval by the investigator or appropriately qualified designee. In all 
cases, the investigator remains accountable for the study data. 
14.2 Monitoring  
It is the responsibility of monitors to:  
● Verify that all participants have been enrolled according to the protocol and that informed 
consent has been obtained prior to any study procedure. 
● Verify that data is authentic, accurate, and complete. 
● Review all eCRFs after data entry 
● Verify that study files, the participant files, source documents, eCRFs, any SAE forms, 
product logs, and laboratory records are completed properly to ensure that the study is 
being conducted according to the protocol and GCP.  
● Safety and rights of participants are being protected throughout the study. 
● Study is conducted in accordance with the currently approved protocol, any other study 
agreements, GCP and all applicable regulatory requirements. 
Direct access to all study-site related and source data is mandatory for the purpose of monitoring 
review. The investigators and the head of the medical institutions (where applicable) agrees to 
allow the monitor direct access to all relevant documents. 
The investigators must ensure provision of reasonable time, space and qualified personnel for 
monitoring visits. 

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Upon completion or premature discontinuation of the study, the monitor will conduct site closure 
activities with the investigators or site staff, as appropriate, in accordance with applicable 
regulations, GCP, and ANMAT procedures. 
14.3 Record Retention 
Following closure of the study, the investigators must maintain all site’s study records (except 
for those required by local regulations to be maintained elsewhere) in a safe and secure location. 
The records must be easily accessible, when needed (e.g. audit or inspection), and must be 
available for review in conjunction with assessment of the facility, supporting systems, and staff. 
Where permitted by applicable laws/regulations or institutional policy, some or all of these 
records can be maintained in a validated format other than hard copy (e.g. microfiche, scanned, 
electronic); however, caution needs to be exercised before such action is taken. The investigators 
must ensure that all reproductions are legible and are a true and accurate copy of the original and 
meet accessibility and retrieval standards, including re-generating a hard copy, if required. 
Furthermore, the investigators must ensure that an acceptable back-up of the reproductions exists 
and that there is an acceptable quality control procedure in place for making these reproductions. 
The investigators/institutions should seek the written approval of the Sponsor before proceeding 
with the disposal of these records after the indicated time period for record retention. The 
minimum retention time will meet the strictest standard applicable to a particular site, as dictated 
by ICH GCP, any institutional requirements, applicable laws or regulations, 
standards/procedures; otherwise, the minimum retention period will default to 10 years. 
The investigators/institutions must notify the Sponsor of any changes in the archival 
arrangements, including, but not limited to, archiving at an off-site facility or transfer of 
ownership of the records in the event the investigator leaves the site. 
14.4 Quality assurance 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory inspection 
of this study. Such audits/inspections can occur at any time during or after completion of the 
study. If an audit or inspection occurs, the investigators and institutions agree to allow the 
auditor/inspector direct access to all relevant documents and to allocate his/her time and the time 
of his/her staff to the auditor/inspector to discuss findings and any relevant issues. 
14.5 Posting of information on publicly available clinical trial registers 
Study information from this protocol will be publicly available on clinicaltrials.gov before 
enrolment of participants begins. 

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14.6 Provision of study results to investigators 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report. The investigator will have access to statistical 
tables, figures, and relevant reports, and will have the opportunity to review the complete study 
results at a site or other mutually agreeable location. 
The investigator is encouraged to share the summary results with the study participants, as 
appropriate. 
 
 

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References 
[1] 
Coronavirus COVID-19 Global Cases by the Center for Systems Science and 
Engineering (CSSE) at Johns Hopkins University (JHU). https://coronavirus.jhu.edu/map.html/. 
Accessed 27 July 2020. 
[2] 
Zhu, Feng-Cai et al. Immunogenicity and safety of a recombinant adenovirus type-5-
vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-
blind, placebo-controlled, phase 2 trial. The Lancet [J] 2020; S0140-6736(20)31605-6 
[3] 
Folegatti, Pedro MAboagye, Jeremy et al. Safety and immunogenicity of the ChAdOx1 
nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, 
randomised controlled trial. The Lancet [J] 2020; https://doi.org/10.1016/ S0140-
6736(20)31604-4 
[4] 
ModernaTX, Inc. A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-
1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19. Phase IIB Clinical 
Trial https://clinicaltrials.gov/ct2/show/study/NCT04470427 
[5] 
 Zhu, Feng-Cai et al. Safety, tolerability, and immunogenicity of a recombinant 
adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, 
first-in-human trial. The Lancet, Volume 395, Issue 10240, 1845 - 1854 
[6] 
Zhu FC, Hou LH, Li JX, et al. Safety and immunogenicity of a novel recombinant 
adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a 
randomised, double-blind, placebo-controlled, phase 1 trial [J]. Lancet, 2015 385:2272-79. 
[7] 
Li JX, Hou LH, Meng FY, et al. Immunity duration of a recombinant adenovirus type-5 
vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in 
China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Glob 
Health [J] 2017; 5: e324–34. 
[8] 
Wu L, Zhang Z Gao H, et al. Open-label phase I clinical trial of Ad5-EBOV in Africans 
in China. Human Vac & Immunother. 2017, 13 (9): 2078–2085. 
[9] 
Zhu FC, Wurie AH, Hou LH, et al. Safety and immunogenicity of a recombinant 
adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, 
randomised, double-blind, placebo-controlled, phase 2 trial. Lancet [J] 2017; 389: 621–28. 
[10]  
CanSino Biologics Inc. Investigator’s Brochure; Recombinant Novel Coronavirus 
Vaccine (Adenovirus Type 5 Vector). 13 23 August 2020.  
[11] 
Cox, D. R. “Regression Models and Life Tables,” Journal of the Royal Statistical Society, 
(1972), Series B, 20, 187–220, with discussion.  
[12]  
Kalbfleisch, J. D. and Prentice, R. L. The Statistical Analysis of Failure Time Data, New 
York: John Wiley and Sons (1980.  

Protocol FH-58 (AD5NCOV-HIV2b)  
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[13] 
Schoenfeld, D. The asymptotic properties of nonparametric tests for comparing survival 
distributions. Biometrika, (1981), 68(1), 316-319.  
[14] 
 Jennison, C., and Turnbull, B. W. Group sequential methods with applications to clinical 
trials. CRC Press. (1999) 
[15]  
Fleiss, J. L., Levin, B., and Paik, M. C. Statistical methods for rates and proportions. John 
Wiley and Sons. (2013). 
[16] 
Munoz F, et al. Brighton Collaboration. Vaccine-associated Enhanced Disease: Case 
definition and Guidelines for Data Collection, Analysis, and Presentation of 
Immunization Safety Data. Vaccine. https://brightoncollaboration.us/vaed/