Clinical trial NCT05184062
Conditions: Coronavirus Disease 2019 (COVID-19)
Keywords: Coronavirus COVID-19 AZD7442
Sponsor: AstraZeneca
Start date: 2021-12-03; Completion date: 2023-05-06
Enrollment: 272 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate the safety and tolerability of a single dose of 600 mg AZD7442 administered IV (intravenous) to Chinese adults (including those with stable medical conditions).

Detailed description:
A Phase II, randomised, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD7442 for administration to prevent and treat coronavirus disease 2019 (COVID-19) in Chinese adult participants (including healthy participants as well as participants with stable medical conditions), approximately 479 days in duration for each participant.

Arms: arm 1: co-administration of a single dose of 600 mg AZD7442 (300 mg AZD8895 and 300 mg AZD1061) by intravenous (IV) infusion. arm 2: co-administration of a single dose of 600mg placebo by intravenous (IV) infusion.
Interventions: intervention 1: 600 mg AZD7442 IV intervention 2: 600mg placebo IV
Intervention descriptions: intervention 1: Participants will be randomized to receive co-administration of 600 mg AZD7442 (300 mg AZD8895 and 300 mg AZD1061) by a single IV infusion. intervention 2: Participants will be randomized to receive co-administration of 600mg placebo by a single IV infusion.

Protocol documents:
Prot_000.pdf: 
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Clinical Study Protocol
Study Intervention
AZD7442
Study Code
D8850C00008
Version
2.0
Date
27Aug2021
A Phase II Double-blind, Placebo-controlled Study to Evaluate the 
Safety and Tolerability of AZD7442 in Chinese Adults
Sponsor Name: AstraZeneca AB
Legal Registered Address: 151 85 Södertälje, Sweden
Regulatory Agency Identifier Number(s): 2021L90010; 2021L90011
This Clinical Study Protocol has been subject to a peer review according to AstraZeneca 
Standard procedures. The Clinical Study Protocol is publicly registered and the results are 
disclosed and/or published according to the AstraZeneca Global Policy on Bioethics and in 
compliance with prevailing laws and regulations.


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Protocol Number: D8850C00008
Amendment Number: 1
Study Intervention: AZD7442, a combination product of 2 monoclonal antibodies 
(AZD8895 and AZD1061)
Study Phase: Phase II
Short Title: A Phase II Double-blind, Placebo-controlled Study of AZD7442 in Chinese 
Adults
Study Physician Name and Contact Information will be provided separately
National Coordinating Investigator Name and Contact Information:
Coordinating Principal Investigator Name and Contact Information:
PPD
PPD


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 1 (CSP version 2.0)
27Aug2021
Original Protocol (CSP version 1.0)]
30Mar2021
AMENDMENT 1 27 AUGUST 2021
Overall Rationale for the Amendment
The primary rationale for this amendment is to revise the inclusion/exclusion criteria to allow 
enrolment of participants who have previously received a COVID-19 vaccine (excluded if 
vaccine was administered within 6 months prior to randomisation). Considering the increased 
COVID-19 vaccination roll-out in China, vaccinated participants will be eligible for the study 
and are expected to comprise a majority of participants (non-vaccinated participants are 
expected to be no more than 35% of the study population). According to China Guideline for 
Clinical Evaluation of COVID-19 Vaccines (Draft), 6 months protection should be provided
(NMPA 2020). Therefore, for eligibility in the study, a minimum interval of 6 months between 
receipt of the COVID-19 vaccine and dosing with AZD7442 is considered adequate to 
minimise potential complication/interference in PK/PD and safety evaluation of AZD7442. 
Additional changes were made to incorporate leading site comments, including revisions to 
PK parameters (primarily formatting) and to add name and contact information for the 
Coordinating Principal Investigator.
Section number and name
Description of change a
Brief rationale for change
Cover page
Added the clinical trial approval number.
Added as approval number 
is available.
Cover page
Added the name and contact information of 
Coordinating Principal Investigator.
Updated based on 
discussion with leading site 
investigators.
1.1 (Synopsis)
For disclosure statement, updated “treatment 
study” to “parallel-group safety and tolerability 
study.”
Updated per sponsor 
standard wording and 
clarification.
1.3 (Schedule of 
Activities)/Table 1 (Schedule 
of Activities: Screening 
Period)
Added row to confirm vaccination status 
(vaccinated or non-vaccinated) for COVID-19 
and vaccination dates (if applicable).
Per exclusion criterion 17, 
participants must not have 
received COVID-19 
vaccine within 6 months 
prior to randomisation.


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Section number and name
Description of change a
Brief rationale for change
1.2 (Schema)/Figure 2 (Study 
Flow Chart)
1.3 (Schedule of 
Activities)/Table 1 (Schedule 
of Activities: Screening 
Period) and Table 2 
(Schedule of Activities: 
Intervention and Follow-up 
Periods)
Figure 2 (footnote b), Table 1 (footnote c), 
Table 2 (footnote k): Revised that SARS-CoV-
2 qRT-PCR is required within 14 days prior to 
randomisation, and results from this test must 
be negative before randomisation. 
Figure 2 (footnote b), Table 1 (footnote c): 
Added that non-vaccinated participants with 
positive SARS-CoV-2 serology should not be 
randomised.
Footnotes revised to be 
consistent with the changes 
to criterion 4 in Section 5.1 
(Inclusion Criteria) and 
criterion 5 in Section 5.2 
(Exclusion Criteria).
1.3 (Schedule of 
Activities)/Table 2 (Schedule 
of Activities: Intervention 
and Follow-up Periods)
Table 2 (footnote h): Updated “end of infusion” 
to “end of infusion, ± 3 minutes)” (bold 
indicates added text).
Revised to specify a 
3-minute window for end 
of infusion.
1.3 (Schedule of Activities)/
Table 2 (Schedule of 
Activities: Intervention and 
Follow-up Periods)
Table 2 (footnote j): Changed “collected” to 
“analysed”.
Reworded for clarification.
2.2 (Background)
Updated with information on new variants, 
latest information on pandemic in China as of 
26 July 2021, and COVID-19 vaccination 
estimates in China as of July 2021.
Updated information for preliminary data of 
AZD7442 neutralisation of SARS-CoV-2 
variants of concern, variants of interest, and 
WHO variant alerts.
Updated to reflect most 
recent information.


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Section number and name
Description of change a
Brief rationale for change
2.3.2 Benefit Assessment)
Added “In the STORM CHASER trial in adults 
who had been potentially exposed to a SARS-
CoV-2 positive individual, AZD7442 reduced 
the risk of developing symptomatic COVID-19 
by 33% (95% CI: -26, 65) compared to 
placebo, which was not statistically significant. 
In a pre-planned analysis of SARS-CoV-2 PCR 
positive (detectable virus) and PCR negative 
(no detectable virus) participants, AZD7442 
reduced the risk of developing symptomatic 
COVID-19 by 73% (95% CI: 27, 90) compared 
with placebo, in participants who were PCR 
negative at time of dosing (AstraZeneca 
2021a).
In the PROVENT pre-exposure prophylaxis 
trial in adults who have increased risk for 
inadequate response to active immunisation 
(predicted poor responders to vaccines or 
intolerant of vaccine) or having increased risk 
for SARS-CoV-2 infection, AZD7442 reduced 
the risk of developing symptomatic COVID-19 
by 77% (95% CI: 46, 90), compared to placebo
(AstraZeneca 2021b).”
Provide updated efficacy 
data from AstraZeneca 
press releases for 
STORMCHASER and 
PROVENT global Phase 3 
studies.
1.1 (Synopsis)
3 (Objectives and Endpoints)
For the primary objective revised to “6 months 
after administration” and for the first 
secondary objective, revised to “15 months 
after administration” (bold indicates added 
text).
Updated for clarity.
1.1 (Synopsis)
3 (Objectives and Endpoints)
4.3 (Justification for Dose)
8.5.1.2 (Pharmacokinetic 
Parameters)
Revised PK parameters, primarily to reformat 
subscript as regular text. Changes include:
•
“Cmax” to “Cmax”
•
“AUC0-180days” to “AUC(0-180days)”
•
“AUClast” to “AUClast”
•
“AUCinf” to “AUCinf”
•
“t½λz” to “t½λz”
•
“tlast” to “tlast”
•
“Vss” to “Vss”
•
“AUC0-60days” to “AUC(0-60days)”
•
“λz, N” to “λzN”
•
“%AUCextr” to “AUCextr”
Updated the format and 
definition of PK 
parameters based on new 
standard operating 
procedure.
1.1 (Synopsis)
3 (Objectives and Endpoints)
8.5.1.2 (Pharmacokinetic 
Parameters)
Added Vz as additional PK parameter in 
secondary endpoints and the corresponding 
definition.
Added, as Vz is applicable 
for IV cohort.


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Section number and name
Description of change a
Brief rationale for change
3 (Objectives and Endpoints)
Revised SARS-CoV-2 serology exploratory 
efficacy endpoint from “Participants with post-
treatment response (negative at baseline to 
positive at any time post-baseline) for SARS-
CoV-2 antibodies” to “Participants with 
post-treatment response (negative serology at 
baseline to positive at post-baseline [up to on-
study COVID-19 vaccination, if applicable])” 
Revised for clarification 
that serology data after on-
study COVID-19 
vaccination will be 
excluded as both SARS-
CoV-2 infection and 
inactive COVID-19 
vaccine can return positive 
serology result of 
nucleocapsid antibody.
1.1 Synopsis
4.1 (Overall Design)
6.3 (Measures to Minimise 
Bias: Randomisation and 
Blinding)
Revised that randomisation will also be 
stratified by vaccinated status (vaccinated or 
non-vaccinated) for COVID-19 at screening 
and added that non-vaccinated participants are 
expected to be no more than 35% of the study 
population.
Due to increased 
vaccination rates in China, 
the study design and 
inclusion/exclusion criteria 
were modified to allow 
vaccinated participants in 
the study. Randomisation 
will be stratified by 
vaccinated status as well as 
age to ensure 3:1 balanced 
representation of the 
2 treatment arms in each of 
these strata.
4.2 (Scientific Rationale for 
Study Design)
Added rationale for including participants who 
have been previously vaccinated for 
COVID-19 in the study and rationale for 
requiring that such participants were vaccinated 
≥6 months prior to randomisation.
 
Due to increasing 
vaccination rates in China, 
the study design and 
inclusion/exclusion criteria 
were modified to allow 
vaccinated participants in 
the study.
 
 
4.2 (Scientific Rationale for 
Study Design)
Next to last paragraph:
 
 
Revised for clarity per site 
comment.
4.3 (Justification for Dose)
Revised “…the bioavailability of 300 mg IM of 
AZD7442 (based on the 3-month AUC) was 
64.1% and 63% for AZD8895 and AZD1061, 
respectively” to 
“…the bioavailability of 300 mg IM of 
AZD7442 (based on the 271-day AUC) was 
68.54% and 65.79% for AZD8895 and 
AZD1061, respectively.”
Updated bioavailability of 
the AZD7442 300-mg IM 
dose based on the FTIH 
Phase 1 interim CSR 
(D8850C00001).
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Section number and name
Description of change a
Brief rationale for change
5.1 (Inclusion 
Criteria)/Criterion 4
5.2 (Exclusion 
Criteria)/Criterion 5
Inclusion 4: Removed inclusion requirement 
for negative SARS-CoV-2 serology test result 
within 14 days prior to randomisation.
Exclusion 5: Removed exclusion requirement 
for positive SARS-CoV-2 serology test result 
within 14 days prior to randomisation. Added 
note to clarify that “Participants with any 
positive SARS-CoV-2 qRT-PCR result based 
on available data at screening will be excluded. 
Non-vaccinated participants with any positive 
SARS-CoV-2 serology result based on 
available data at screening will be excluded.”
Modified the criteria to 
avoid excluding 
participants who test 
positive for SARS-CoV-2 
serology due to having 
previously received 
COVID-19 vaccination.
5.1 (Inclusion 
Criteria)/Criterion 6
Revised “Male participants: Contraception for 
male participants is not required; however, to 
avoid the transfer of any fluids, all male 
participants must use...” to “Male participants: 
To avoid transfer of fluids to a sexual partner, 
all male participants must use...”
Removed “contraception 
for male participants is not 
required” to avoid 
confusion and to specify 
the exact purpose of 
contraception.
5.2 (Exclusion 
Criteria)/Criterion 6
Revised “on admission” to “randomisation”.
Updated for clarity as term 
“admission” is not 
applicable in this study.
5.2 (Exclusion 
Criteria)/Criteria 16 and 17
Criterion 16: Revised from “Any prior receipt 
of an investigational or licensed vaccine or 
other mAb/biologic indicated for the 
prevention of SARS-CoV-2 or scheduled 
receipt” to
“Any prior receipt of an investigational or 
licensed mAb/biologic indicated for the 
prevention of SARS-CoV-2 or COVID-19 or 
scheduled to receive any investigational or 
licensed mAb/biologic indicated for the 
prevention of SARS-CoV-2 or COVID-19.”
Criterion 17: Added exclusion for “Receipt of 
any COVID-19 vaccine within 6 months prior 
to randomisation or scheduled to receive any 
COVID-19 vaccine.”
Revised to remove 
exclusion for prior receipt 
of COVID-19 vaccine. 
Considering increased roll-
out of COVID-19 vaccine 
in China, only participants 
who have received 
COVID-19 vaccine within 
6 months prior to 
randomisation will be 
excluded from the study. 
At least 6 months are 
required between receipt of 
the COVID-19 vaccine and 
dosing with AZD7442 to 
minimise potential 
complication/interference 
in PK/PD and safety 
evaluation of AZD7442.


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Section number and name
Description of change a
Brief rationale for change
5.4 (Screen Failures)
Revised from “Individuals who do not meet the 
criteria for participation in this study (screen 
failure) may be rescreened. Only one time 
rescreening is allowed in the study under 
exclusion criterion 3 (see criterion 3 of Section 
5.2 for the details)” to 
“Individuals who do not meet the criteria for 
participation in this study (screen failure) may 
be rescreened if the eligibility criterion that 
resulted in screen failure has changed in a 
manner that meets eligibility. Only a single 
rescreening is allowed in the study.”
Revised to not restrict 
rescreening to exclusion 3 
and to allow a single 
rescreening if the eligibility 
criterion that resulted in a 
screen failure has changed 
in a manner that meets 
eligibility.
6.1.1 (Investigational 
Products)/Table 5 
(Investigational Medicinal 
Products)
Updated the Sourcing and Packaging and 
Labelling for placebo to “Provided locally by 
the study site or by the sponsor” (bold 
indicates added text).
To clarify the sourcing and 
packaging for placebo 
might be done by sponsor 
if cannot be provided by 
site.
6.2.1 (Storage and 
Accountability)
Revised number 4 to “… are provided in the 
Investigational Medicinal Product Manual or 
other equivalent documents” (bold indicates 
added text).
Reworded as relevant 
information might be 
included in other 
documents and named 
differently.
6.2.2 (Preparation and 
Administration)
Changed from “…for both AZD8895 and 
AZD1061 infusion.” to “…for both AZD8895 
and AZD1061 infusion and placebo infusion” 
(bold indicated added text).
In step 3: revised text to “Use a coloured 
shading bag or attach labels and cover to the 
IV bags in order to ensure blinding” (bold 
indicates added text).
Revised “3.0 mL” to “3 mL” throughout and 
revised “6.0 mL” to “6 mL”.
Reworded for clarification 
and updated specification 
in blinding step.
6.5.1 (COVID-19 Vaccines)
In third bullet, revised “…the number of 
months identified above for each dose 
represents…” to “…the number of months 
identified above for the dose represents…”
Updated for clarity as there 
is only one dose.
8.1.1 
 
 
)
Added Table 8 “COVID-19 Qualifying 
Symptoms”
Added the table to support 
evaluation and diagnosis 
for COVID-19 monitoring.
8.1.2 
8.5.2 (Pharmacodynamics)
Revised first sentence in Section 8.1.2 and first 
bullet in Section 8.5.2 to “…and will be 
analysed provided the analysis method is 
established and appropriate approval has been 
obtained” (bold indicates added text).
Reworded for clarity.
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Section number and name
Description of change a
Brief rationale for change
8.2.1 (Physical 
Examinations)
Added cross-reference to Section 8.3.6.for AE 
reporting regarding physical examination.
Revised “site-directed physical exam” to 
“symptom-directed physical examination”.
Updated language for 
clarification and to avoid
confusion regarding 
physical examination and 
AE reporting.
8.2.4 (Clinical Safety 
Laboratory Assessments)
Third paragraph: Revised to “…and samples 
for SARS-CoV-2 serology (at screening) and 
SARS-CoV-2 qRT-PCR will be performed at a 
local laboratory at or near the investigational 
site” (bold indicates added text).
Updated for clarity. SARS-
CoV-2 serology test at 
screening is performed 
locally and if site does not 
have feasibility to perform 
the test, results from local 
laboratory at or near the 
investigational site are 
acceptable.
8.2.4 (Clinical Safety 
Laboratory Assessments)
Table 9 (Haematology, Serum Clinical 
Chemistry, Urinalysis, and Coagulation): 
Updated “Urea” to “Urea/blood urea nitrogen 
(BUN)”.
Table 11 (Viral Serology Testing): Revised 
“HIV antigen Antibody” to “HIV”.
Updated based on local 
laboratory practice at sites 
in China.
8.3.6 (Adverse Events Based 
on Examinations and Tests)
Added “Abnormal results of examination and 
tests at screening (eg, haematology, clinical 
chemistry, urinalysis, ECG, physical 
examination, vital signs, etc.) are regarded as 
existing conditions before ICF and will not be 
recorded as AE. Relevant clinically significant 
abnormality of examination and tests during 
screening can be recorded as medical history 
according to investigator’s medical judgment.” 
Added to clarify AE 
reporting requirement at 
screening as per clinical 
practice and discussion 
with site.
8.5 (Human Biological 
Samples)
Updated “Additional use includes but not 
limited to further characterisation of any 
ADAs…” to “Additional use includes further 
characterisation of any ADAs…”
Reworded to be more 
specific on additional use 
as per HGR requirement.
8.5.1.2 (Pharmacokinetic 
Parameters)
Revised first sentence to “Where possible, the 
PK parameters will be estimated for AZD7442 
(each mAb: AZD8895 and AZD1061) based
on serum concentrations” (bold indicates added 
text).
Editorial update.
8.5.1.2 (Pharmacokinetic 
Parameters)
Removed the sentence “Dose normalised 
Cmax, AUCinf, and AUClast will be calculated 
for each mAb: AZD8895 and AZD1061.”
As there is only one dose 
evaluated in the study, dose 
normalised parameters are 
not needed.
8.5.1.2 (Pharmacokinetic 
Parameters)
Updated “actual elapsed times” to “actual times 
after dose”.
Reworded to clarify and to 
avoid misunderstanding.


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Section number and name
Description of change a
Brief rationale for change
1.1 (Synopsis), 9.2 (Sample 
Size Determination)
Moved the sentence “A dropout rate of 20% is 
assumed” to the end of the paragraph. Revised 
to 162 participants (previously 
204 participants) in the AZD7442 group will 
provide a probability of at least 80% to observe 
at least one AE case.
Revised to clarify that 
sample size of 
162 participants is before 
adjusting for the 20% 
dropout rate.
9.3 (Populations for 
Analyses)
Enrolled: Revised “Enrolled” analysis set to 
“All participants” analysis set.
PK analysis set: Revised “evaluable” to 
“quantifiable” and “PK data” to “PK 
observation post-dose”.
PD analysis set: Revised “have evaluable 
SARS-CoV-2 neutralising responses” to “had 
at least one quantifiable titre observation post-
dose”.
Editorial changes for 
clarification.
9.4.3.1 (Primary Endpoint(s))
Revised “any AEs with outcome of death” to 
“any SAE with outcome of death”; revised 
“AEs leading to study withdrawal” to “other 
AE categories as appropriate”.
Revised text from “Summaries will be provided 
taking into consideration the relationship as 
assessed by the investigator, maximum 
intensity, seriousness, death, AEs leading to 
study withdrawal, and AESIs where 
appropriate.…An additional table will present 
the number and percentage of participants with 
the most common AEs. Most common AEs 
will be defined in the SAP” to 
“Summaries may be provided for AEs, SAEs, 
SAEs with outcome of death, AESIs, and other 
AE categories as appropriate. Additional 
summaries will be provided taking into 
consideration the relationship as assessed by 
the investigator as well as maximum intensity.”
Editorial changes to 
simplify the section.
9.4.4 (Pharmacokinetic 
Analyses)
Removed “by dose regimen” in first sentence.
Removed for clarity as 
there is only one dose.
9.4.5 (Pharmacodynamic 
Analyses)
Revised “The serum neutralising responses…” 
to “All available data of serum neutralising 
responses…”
Revised to clarify that all 
available data of serum 
neutralising responses will 
be summarised.
Appendix E (Abbreviations)
Updated to include additional abbreviations.
Editorial updates in 
accordance with the 
updates in CSP body text.


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Section number and name
Description of change a
Brief rationale for change
11 (References)
Updated Gonçalves et al 2020 to “CPT 
Pharmacometrics Syst Pharmacol. 
2020;9(9):509-14.”
Added references for AstraZeneca STORM 
CHASER and PROVENT press releases.
Added NHC 2021 and NMPC reference.
Update and add references
in accordance with the 
updates in CSP body text.
a
All changes are considered as non-substantial.


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TABLE OF CONTENTS
TITLE PAGE........................................................................................................................ 1
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3
TABLE OF CONTENTS .................................................................................................... 12
LIST OF FIGURES ............................................................................................................ 14
LIST OF TABLES .............................................................................................................. 14
LIST OF APPENDICES ..................................................................................................... 15
1
PROTOCOL SUMMARY ................................................................................ 16
1.1
Synopsis ........................................................................................................... 16
1.2
Schema............................................................................................................. 19
1.3
Schedule of Activities ....................................................................................... 20
1.3.1
Order of Assessments........................................................................................ 25
2
INTRODUCTION............................................................................................ 26
2.1
Study Rationale ................................................................................................ 26
2.2
Background ...................................................................................................... 26
2.3
Benefit/Risk Assessment................................................................................... 27
2.3.1
Risk Assessment ............................................................................................... 28
2.3.2
Benefit Assessment........................................................................................... 29
2.3.3
Overall Benefit: Risk Conclusion...................................................................... 30
3
OBJECTIVES AND ENDPOINTS................................................................... 31
4
STUDY DESIGN ............................................................................................. 32
4.1
Overall Design.................................................................................................. 32
4.2
Scientific Rationale for Study Design ............................................................... 33
4.3
Justification for Dose........................................................................................ 34
4.4
End of Study Definition.................................................................................... 35
5
STUDY POPULATION.................................................................................... 35
5.1
Inclusion Criteria .............................................................................................. 35
5.2
Exclusion Criteria ............................................................................................. 38
5.3
Lifestyle Considerations ................................................................................... 40
5.3.1
Meals and Dietary Restrictions ......................................................................... 40
5.3.2
Caffeine, Alcohol, and Tobacco......................................................................... 40
5.3.3
Activity............................................................................................................. 40
5.3.4
Reproduction/Contraception Requirements....................................................... 40
5.4
Screen Failures ................................................................................................. 41
6
STUDY INTERVENTION ............................................................................... 41
6.1
Study Intervention(s) Administered................................................................... 42
6.1.1
Investigational Products.................................................................................... 42


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6.2
Preparation/Handling/Storage/Accountability ................................................... 42
6.2.1
Storage and Accountability ............................................................................... 42
6.2.2
Preparation and Administration......................................................................... 43
6.3
Measures to Minimise Bias: Randomisation and Blinding................................. 45
6.4
Study Intervention Compliance......................................................................... 46
6.5
Concomitant Therapy........................................................................................ 46
6.5.1
COVID-19 Vaccines ......................................................................................... 47
6.6
Dose Modification ............................................................................................ 48
6.7
Intervention After the End of the Study............................................................. 48
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL........................................................... 48
7.1
Discontinuation of Study Intervention............................................................... 48
7.2
Participant Withdrawal from the Study.............................................................. 49
7.3
Lost to Follow-up ............................................................................................. 49
8
STUDY ASSESSMENTS AND PROCEDURES.............................................. 50
8.1
Efficacy Assessments........................................................................................ 50
8.1.1
............................. 50
8.1.2
................................................................. 51
8.2
Safety Assessments........................................................................................... 51
8.2.1
Physical Examinations...................................................................................... 51
8.2.2
Vital Signs ........................................................................................................ 52
8.2.3
Electrocardiograms........................................................................................... 52
8.2.4
Clinical Safety Laboratory Assessments............................................................ 53
8.2.5
Monitoring of Administration of Study Intervention.......................................... 55
8.3
Adverse Events and Serious Adverse Events..................................................... 55
8.3.1
Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information............................................................................................. 55
8.3.2
Follow-up of Adverse Events and Serious Adverse Events................................ 56
8.3.3
Causality Collection.......................................................................................... 56
8.3.4
Adverse Events of Special Interest.................................................................... 57
8.3.5
Adverse Events Based on Signs and Symptoms ................................................ 57
8.3.6
Adverse Events Based on Examinations and Tests ............................................ 57
8.3.7
Hy’s Law.......................................................................................................... 58
8.3.8
Reporting of Serious Adverse Events................................................................ 58
8.3.9
Pregnancy......................................................................................................... 59
8.3.9.1
Maternal Exposure............................................................................................ 59
8.3.9.2
Paternal Exposure............................................................................................. 59
8.3.10
Medication Error............................................................................................... 60
8.4
Overdose .......................................................................................................... 60
8.5
Human Biological Samples............................................................................... 61
8.5.1
Pharmacokinetics.............................................................................................. 61
8.5.1.1
Determination of Drug Concentration ............................................................... 61
8.5.1.2
Pharmacokinetic Parameters ............................................................................. 62
CCI
CCI


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8.5.2
Pharmacodynamics........................................................................................... 63
8.5.3
Immunogenicity Assessments ........................................................................... 63
8.6
Human Biological Sample Biomarkers ............................................................. 63
8.7
Optional Genomics Initiative Sample................................................................ 63
8.8
Medical Resource Utilisation and Health Economics ........................................ 63
9
STATISTICAL CONSIDERATIONS................................................................ 63
9.1
Statistical Hypotheses....................................................................................... 63
9.2
Sample Size Determination............................................................................... 63
9.3
Populations for Analyses................................................................................... 65
9.4
Statistical Analyses ........................................................................................... 65
9.4.1
General Considerations..................................................................................... 66
9.4.2
Efficacy ............................................................................................................ 66
9.4.3
Safety ............................................................................................................... 66
9.4.3.1
Primary Endpoint(s).......................................................................................... 67
9.4.3.2
Other Safety Endpoint(s) .................................................................................. 67
9.4.4
Pharmacokinetic Analyses ................................................................................ 67
9.4.5
Pharmacodynamic Analyses.............................................................................. 68
9.4.6
Immunogenicity Analyses................................................................................. 68
9.5
Interim Analyses............................................................................................... 68
9.6
Data Safety Monitoring Board .......................................................................... 68
10
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL
CONSIDERATIONS ........................................................................................ 69
11
REFERENCES................................................................................................. 91
LIST OF FIGURES
Figure 1
Study Design ........................................................................................... 19
Figure 2
Study Flow Chart..................................................................................... 19
LIST OF TABLES
Table 1
Schedule of Activities: Screening Period ................................................. 20
Table 2
Schedule of Activities: Intervention and Follow-up Periods ..................... 22
Table 3
Objectives and Endpoints......................................................................... 31
Table 4
Highly Effective Methods of Contraception............................................. 37
Table 5
Investigational Medicinal Products .......................................................... 42
Table 6
Required Vials of AZD7442 (AZD8895 and AZD1061).......................... 44


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Table 7
Summary of Medications and Treatments Permitted, Prohibited, and 
Restricted During the Study..................................................................... 47
Table 8
COVID-19 Qualifying Symptoms............................................................ 51
Table 9
Haematology, Serum Clinical Chemistry, Urinalysis, and Coagulation .... 54
Table 10
Pregnancy Testing (Females Only) .......................................................... 54
Table 11
Viral Serology Testing............................................................................. 55
Table 12
SARS-CoV-2 Testing .............................................................................. 55
Table 13
Populations for Analysis .......................................................................... 65
LIST OF APPENDICES
Appendix A
Regulatory, Ethical, and Study Oversight Considerations......................... 70
Appendix B
Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ........................................................................ 76
Appendix C
Handling of Human Biological Samples .................................................. 81
Appendix D
Actions Required in Cases of Increases in Liver Biochemistry and 
Evaluation of Hy’s Law........................................................................... 83
Appendix E
Abbreviations .......................................................................................... 89


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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title
A Phase II Double-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of 
AZD7442 in Chinese Adults
Short Title
A Phase II Double-blind, Placebo-controlled Study of AZD7442 in Chinese Adults
Rationale
 
AZD7442 is currently being evaluated for 
administration to prevent and treat coronavirus disease 2019 (COVID-19) in global late stage 
studies. This Phase II study will gather additional safety and tolerability data of AZD7442 in 
the Chinese population.
Objectives and Endpoints
Objectives
Endpoints
Primary
•
To evaluate the safety and tolerability of a 
single dose of 600 mg AZD7442 administered 
IV to Chinese participants (including those with 
stable medical conditions) ≥
 of age at 
6 months after administration
•
AEs, SAEs, AESIs, safety laboratory parameters 
(haematology, clinical chemistry, coagulation, 
and urinalysis); 12-lead ECG; vital signs (blood 
pressure, pulse rate, body temperature, and 
respiratory rate)
Secondary
•
To evaluate the safety and tolerability of a 
single dose of 600 mg AZD7442 administered 
IV to Chinese participants (including those with 
stable medical conditions) ≥
 of age at 
15 months after administration
•
AEs, SAEs, AESIs, safety laboratory parameters 
(haematology, clinical chemistry, coagulation, 
and urinalysis); 12-lead ECG; vital signs (blood 
pressure, pulse rate, body temperature, and 
respiratory rate)
•
To evaluate the serum PK of AZD8895 and 
AZD1061 after a single dose of 600 mg 
AZD7442 administered IV
Where possible, PK parameters will be assessed for 
individual mAbs (AZD8895 and AZD1061):
•
Cmax, AUC(0-180days)
•
Additional PK parameters that may be 
determined when appropriate include:
!
AUClast, AUCinf, t½λz, tlast, Vss, Vz, and 
CL
PPD
PPD
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Objectives
Endpoints
•
To evaluate the ADA responses to AZD7442 in 
serum
•
Presence of ADA to AZD8895 and AZD1061 in
serum
Blood samples will be collected and stored for 
analysis of ADAs. Unscheduled samples for ADA 
analysis may be collected in response to suspected 
immune-related AEs.
ADA, antidrug antibody; AE, adverse event; AESI, adverse event of special interest; AUC(0-180days), area 
under the concentration-time curve from time zero to 180 days; AUCinf, area under the concentration-time curve 
from time zero to infinity; AUClast, area under the concentration-time curve from time zero to time of last 
measurable concentration; CL, clearance; Cmax, maximum concentration; ECG, electrocardiogram; 
IV, intravenous; mAb, monoclonal antibody; PK, pharmacokinetics; SAE, serious adverse event; t½λz, terminal 
elimination half-life, estimated as (ln2)/∀z; tlast, time of last quantifiable concentration; Vss, volume of 
distribution at steady state; Vz, volume of distribution based on terminal phase.
For exploratory objectives and endpoints, see Section 3 of the protocol.
Overall Design
This is a Phase II, randomised, double-blind, placebo-controlled study to evaluate the safety, 
tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD7442 in Chinese 
adult participants ≥
 of age, including healthy participants as well as participants with 
stable medical conditions. The study will be conducted in clinical study centres in mainland 
China.
Approximately 272 participants, who fulfil the study eligibility criteria will be randomised in 
a 3:1 ratio to receive a single dose of study intervention administered by intravenous (IV) 
infusion, either 600 mg AZD7442 (204 participants) or placebo (68 participants). 
Randomisation will be stratified by 
 
 at screening. Considering the increased 
vaccination roll-out in China, non-vaccinated participants are expected to be no more than 
35% of the study population.
Participants will then be monitored for approximately 15 months after dosing (through 
Day 451) for safety, including the recording of adverse events (AEs), AEs of special interest, 
and serious AEs, and the collection of blood samples for PK, PD, and antidrug antibodies.
Disclosure Statement
This is a parallel-group safety and tolerability study with 2 arms that is participant- and 
investigator-blinded.
Number of Participants
Approximately 272 participants will be randomised 3:1 to study intervention with 600 mg 
AZD7442 (n = 204) or placebo (n = 68) administered IV. If the true AE rate is 1% at the 
primary time point (ie, Month 6), 162 participants in the AZD7442 group will provide a 
PPD
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probability of at least 80% to observe at least one AE case. A dropout rate of 20% is assumed.
The 1% assumption is driven by the international convention where 1% is used as the lower 
limit of common AEs (between infrequent and frequent AEs) (CIOMS 1999). The 
randomisation ratio of 3:1 limits the number of participants in the placebo group so that 
adequate information can be obtained to objectively assess the safety of AZD7442 in the 
Chinese population.
Note: “Enrolled” means a participant's, or their legally acceptable representative’s, agreement 
to participate in a clinical study following completion of the informed consent process. 
Potential participants who are screened for the purpose of determining eligibility for the study, 
but are not randomly assigned in the study, are considered “screen failures”, unless otherwise 
specified by the protocol.
Intervention Groups and Duration
The study is expected to be approximately 479 days in duration for each participant, 
consisting of a screening period of up to 28 days (Days -28 through -1), an intervention period 
of one day (Day 1 [randomisation and dosing]), and a safety follow-up period of 450 days 
(Days 2 through 451).
On Day 1, participants will receive a single dose of study intervention (AZD7442 or placebo) 
according to their randomised treatment assignment. The study intervention will be 
co-administered as a single IV infusion containing both mAbs (AZD8895 and 
AZD1061)/placebo.
Data Safety Monitoring Board
An independent Data Safety Monitoring Board (DSMB) will provide oversight, to ensure safe 
and ethical conduct of the study. The DSMB will have the responsibility of evaluating 
cumulative safety and other clinical trial data at regular intervals and making appropriate 
recommendations based on the available data.
Statistical Methods
Unless otherwise stated, the as-treated principle will be applied to study evaluations, which is 
participants who received study intervention other than the one assigned by randomisation 
will be analysed as belonging to the actual intervention received.
No statistical hypotheses will be evaluated based on formal statistical tests. Descriptive 
statistics will be presented for relevant data and parameters. See Section 9 of the protocol for 
further details.
The primary database lock (DBL) will occur after all treated participants have completed 
follow-up through Day 181 to conduct the primary analysis. No early stopping decision will 


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be made for futility or superiority at the primary analysis. A final DBL will occur when all 
participants have completed the study (ie, completed follow-up through Day 451) to conduct 
the final analysis. As safety evaluation is the primary objective and no multiplicity control is 
applied, ad-hoc interim analyses may be performed for additional evaluation of a potential 
signal in the safety profile.
1.2
Schema
The overall study design is presented in Figure 1. The study flow chart is presented in 
Figure 2.
Figure 1
Study Design
IV, intravenous; pt, participant; R, randomisation.
Figure 2
Study Flow Chart
a
Visit 1 may be conducted over one or more days during the screening period.
b
Participants must be tested for SARS-CoV-2 infection by qRT-PCR within 14 days prior to randomisation, 
and results must be negative before randomisation. Additionally, non-vaccinated participants with positive 
SARS-CoV-2 serology should not be randomised.
c
On-site visits during follow-up occur from Day 8 (Visit 3) through Day 361 (Visit 9). On Day 451, 
participants will be contacted by phone for safety follow-up.
IV, intravenous; qRT-PCR, quantitative reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe 
acute respiratory syndrome coronavirus 2.


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1.3
Schedule of Activities
The Schedule of Activities (SoA) for the study is presented in the following tables:
#
Screening period: Table 1
#
Intervention and follow-up periods: Table 2
Table 1
Schedule of Activities: Screening Period
Study period
Screening
Details in section 
of CSP
Visit
Visit 1
Procedure 
Day -28 to Day -1
Written informed consent/assignment of 
enrolment code
X
5.1, Appendix A 3
Medical history and demographics
X
5.1, 5.2
Full physical examination, height, weight, and 
BMI
X
5.1, 8.2.1
12-Lead ECG
X
5.1, 8.2.3
Vital signs a
X
5.1, 8.2.2
Serum chemistry
X
5.1, 5.2, 8.2.4
Haematology
X
5.1, 5.2, 8.2.4
Coagulation
X
5.1, 5.2, 8.2.4
FSH (suspected postmenopausal women 
< 50 years only)
X
5.1, 5.2, 8.2.4
Urinalysis
X
5.1, 5.2, 8.2.4
Pregnancy test (serum β-hCG); FOCBP only b
X
5.1, 5.2, 8.2.4, 
8.3.9, 8.3.9.1
HIV, hepatitis B, hepatitis C testing
X
5.2, 8.2.4
History of drug and alcohol abuse
X
5.2
Assessment of AEs/SAEs
X
5.2, 8.3
Concomitant therapies
X
5.2, 6.5
Confirm vaccination status (vaccinated or 
non-vaccinated) for COVID-19 and vaccination 
dates (if applicable)
X
5.2
SARS-CoV-2 serology and qRT-PCR c
X
5.1, 5.2, 8.2.4
Monitoring for COVID-19 symptoms and 
exposure history d
X
5.1, 8.1.1
Verify eligibility criteria
X
5.1, 5.2
a
The following variables will be collected after the participants have rested in the supine position for at least 
5 minutes: Systolic BP, diastolic BP, pulse rate, body temperature, and respiratory rate.
b
Pregnancy test must be negative at screening.


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c
Participants must be tested for SARS-CoV-2 infection by qRT-PCR within 14 days prior to randomisation, 
and results must be negative before randomisation. Additionally, non-vaccinated participants with positive 
SARS-CoV-2 serology should not be randomised.
d
A negative SARS-CoV-2 qRT-PCR retest result is required if participant has symptoms of infection or if 
participant has any known/suspected exposure after the initial test.
AE, adverse event; β-hCG, beta human chorionic gonadotropin; BMI, body mass index; BP, blood pressure; 
COVID-19, corona virus disease 2019; CSP, clinical study protocol; ECG, electrocardiogram; FOCBP, females 
of childbearing potential; FSH, follicle stimulating hormone; HIV, human immunodeficiency virus; qRT-PCR, 
quantitative reverse transcriptase polymerase chain reaction; SAE, serious adverse event.


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Table 2
Schedule of Activities: Intervention and Follow-up Periods
Study period
Intervention
Follow-up
Details 
in 
section 
of CSP
Study visit
V2
V3
V4
V5
V6
TPV a
V7
TPV a
V8
TPV a
V9/EDV
TPV a
Study day
D1
pre-dose
D1
post-dose
D8
D31
D61
D91
D121
D151
D181
D211
D241
D271
D301
D331
D361
D451
Procedure / visit 
window
-1d
-2d
± 5d
± 5d
± 10d
± 5d
± 10d
± 10d
± 10d
± 10d
± 10d
Medical history
X b
5.1, 5.2
Brief physical 
examination
X b
8.2.1
Full physical 
examination
X
X
X
X
8.2.1
Weight
X
X
8.2.1
12-lead ECG c
X
X
X
8.2.3
Vital signs
X d
X d
X e
X e
X e
X e
X e
X e
X e
8.2.2
Serum chemistry
X
X
X
X
X
8.2.4
Haematology
X
X
X
X
X
8.2.4
Coagulation
X
X
X
X
X
8.2.4
Urinalysis
X
X
X
X
X
8.2.4
Pregnancy test 
(urine hCG); 
FOCBP only
X f
X
X
X
X
X
X
8.2.4, 
8.3.9.1
PK serum sample
X g
X h
X i
X i
X i
X i
X i
X i
X i
8.5.1
ADA serum sample
X g
X
X
X
X
8.5.3
Neutralising 
antibody serum 
sample j
X g
X
X
X
X
X
X
X
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Table 2
Schedule of Activities: Intervention and Follow-up Periods
Study period
Intervention
Follow-up
Details 
in 
section 
of CSP
Study visit
V2
V3
V4
V5
V6
TPV a
V7
TPV a
V8
TPV a
V9/EDV
TPV a
Study day
D1
pre-dose
D1
post-dose
D8
D31
D61
D91
D121
D151
D181
D211
D241
D271
D301
D331
D361
D451
Procedure / visit 
window
-1d
-2d
± 5d
± 5d
± 10d
± 5d
± 10d
± 10d
± 10d
± 10d
± 10d
Serum sample for 
SARS-CoV-2 
serology central 
testing j
X g
X
X
8.1.2
Assessment of 
AEs/SAEs
X (ongoing observation and questioning)
X
8.3
Concomitant 
therapies
X (ongoing observation and questioning)
X
6.5
Monitoring for 
COVID-19 
symptoms and 
exposure history
X k
X (ongoing observation and questioning) l
8.1.1
SARS-CoV-2 
qRT-PCR k, l
If clinically indicated
8.1.1, 
8.2.4
Verify eligibility 
criteria
X
5.1, 5.2
Randomisation k
X
4.1, 6.3
Study intervention 
administration
X
6.1.1, 
6.2.2
a
Telephone contact for safety monitoring.
b
Update screening medical history and physical examination (any new findings since screening).
c
ECGs will be obtained after at least 5 minutes supine rest.


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d
On Day 1, vital signs (systolic BP, diastolic BP, pulse rate, body temperature, and respiratory rate) will be monitored before and after administration of 
study intervention. Time points will include pre-dose (up to 120 minutes prior to start of infusion), completion of infusion (0-~ 5 minutes), 30 (± 5) minutes, 
60 (± 5) minutes, 90 (± 5) minutes, and 120 (± 5) minutes post completion of infusion.
e
Any abnormal vital signs must be repeated after the participant has been at rest for at least 5 minutes.
f
Pregnancy test must be negative prior to randomisation.
g
Pre-dose sample (up to 90 minutes prior to start of infusion).
h
PK serum sample should be collected when the infusion is complete (end of infusion, ± 3 minutes). The actual end time of infusion completion (duration of 
infusion) should be recorded.
i
PK serum samples will not be collected once a participant is unblinded and found to be on placebo arm.
j
Serum sample for neutralising antibody and serum sample for SARs-CoV-2 serology will only be analysed if the analysis method is established and 
appropriate approval has been obtained.
k
Participants must be tested for SARS-CoV-2 infection by qRT-PCR within 14 days prior to randomisation, and results must be negative before 
randomisation. A negative SARS-CoV-2 qRT-PCR and serology retest result is required if participant has symptoms of infection or if participant has any 
known/suspected exposure after the initial test.
l
After Day 1, if participant has symptoms of infection or if participant has any known/suspected exposure, SARS-CoV-2 qRT-PCR should be performed at 
the discretion of the investigator.
AE, adverse event; ADA, antidrug antibodies; BP, blood pressure; COVID-19, coronavirus disease 2019; CSP, clinical study protocol; D/d, day; 
ECG, electrocardiogram; EDV, early discontinuation visit; FOCBP, females of childbearing potential; hCG, human chorionic gonadotropin; 
PK, pharmacokinetic(s); qRT-PCR, quantitative reverse transcriptase polymerase chain reaction; SAE, serious adverse event; SARS-CoV-2, severe acute 
respiratory syndrome coronavirus 2; TPV, telephone visit; V, visit.


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1.3.1
Order of Assessments
It is important that PK sampling occurs as closely as possible to the scheduled time. To 
achieve this, other assessments scheduled at the same time will be initiated prior to/following 
the PK time point. The sequence at a particular time point is:
1
12-lead safety ECGs
2
Vital signs (systolic and diastolic blood pressure, pulse rate, body temperature, and 
respiratory rate)
3
PK and safety blood samples (will be collected at the specified time point)
4
Other procedures


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2
INTRODUCTION
AZD7442 is a combination of 2 recombinant human IgG1 kappa mAbs, AZD8895 and 
AZD1061, directed against the RBD of the spike protein of SARS-CoV-2. AZD7442 is being 
developed for the prophylaxis and treatment of COVID-19.
2.1
Study Rationale
AZD7442 is currently being evaluated for administration to prevent and treat COVID-19 in 
global late-stage studies. This Phase II study will gather additional safety and tolerability data 
of AZD7442 in the Chinese population.
2.2
Background
SARS-CoV-2 is a newly emerged CoV responsible for the current COVID-19 global 
pandemic. The SARS-CoV-2 spike protein contains the virus’s RBD, which enables the virus 
to bind to receptors on human cells. Unlike the majority of CoVs that cause mild disease in 
humans and animals, SARS-CoV-2 can replicate in the lower respiratory tract to cause acute 
respiratory distress syndrome and fatal pneumonia. This is also a characteristic of the 
genetically-similar SARS-CoV and the more distantly related MERS-CoV, both of which were 
responsible for prior outbreaks in 2002 to 2003 and 2012, respectively (Gorbalenya et al 
2020). With a basic R0 value estimated between 2.43 to 3.10, SARS-CoV-2 is highly 
transmissible from person to person, which has contributed to its rapid dissemination 
worldwide (D’Arienzo and Coniglio 2020). As of 15 August 2021, there have been 
approximately 206 million confirmed cases of COVID-19, including approximately 
4.4 million deaths, reported to the World Health Organisation (WHO 2021).
Several variants have been identified, such as B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 
(Delta), and P.1 (Gamma), which are classified as variants of concern (WHO 2021, US CDC 
2021). These variants contain multiple spike protein mutations and mutations in other 
genomic regions. While it is known and expected that viruses constantly change through 
mutation leading to the emergence of new variants, preliminary analysis in the UK suggests 
that variant B.1.1.7 is significantly more transmissible than previously circulating variants, 
with an estimated potential to increase the R0 by 0.4 or greater with an estimated increased 
transmissibility of up to 70% (WHO 2021, ECDC 2020). Variant B.1.1.7 has been detected in 
190 countries including China (WHO 2021).
To date, the COVID-19 pandemic is under control in China with approximately 767 cases 
between 09 to15 August 2021, which includes imported cases and clusters of new cases in 
several cities (WHO 2021). With the emergence of new variants, there are risks to the new 
imported cases spreading due to their high transmissibility. Strict preventative measures to 
control local transmission and transmission from imported cases are in place to prevent 
spreading. However, the strict preventative measures require constant vigilance and expend 


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significant resources throughout China. The China border is currently open to allow 
international travel with restrictions (eg, China residency or work permits), and it is 
anticipated that, eventually, such restrictions will be lifted. Thus, efficacious and safe options 
for prophylaxis and treatment of COVID-19 are needed to mitigate the risks of uncontrolled 
spreading and future outbreaks due to international travel.
To bring this COVID-19 pandemic to an end, vaccines are developed and provided for people 
worldwide. Overall, more than 1.5 billion vaccines have been administered in China by July 
2021 (NHC 2021).
Effective interventions to treat and prevent COVID-19 remain few in number and clinical 
experience is limited. Current clinical management is primarily limited to supportive care. 
Under these clinical circumstances, there is a high need for drugs that can be used from before 
or during the SARS-CoV-2 infection to prevent severe illness. High-risk populations 
(pre-exposure prevention) and people who may have been in close contact with those 
confirmed to have SARS-CoV-2 infection may benefit from prophylactics due to the rapid 
onset of preventive effect by eradicating the viral load earlier than accomplished by the innate 
and acquired immune responses.
AZD7442 is a combination of 2 mAbs (AZD8895 and AZD1061), with distinct binding sites, 
directed 
. The use 
of 2 mAbs provides redundancy in protection in case of virus mutation and escape.
Preliminary data have been generated demonstrating that AZD7442 neutralises SARS-CoV-2 
variants of concern (Alpha, B.1.1.7; Beta, B.1.351; Gamma, P.1; and Delta, B.1.617.2), 
variants of interest (Eta, B.1.525; Iota, B.1.526; Kappa, B.1.617.1; and Lambda, C.37), and 
several WHO variant alerts for further monitoring (Epsilon, B.1.427 / B.1.429; Zeta, P.2; R.1; 
and B.1.1.519) in live virus and/or pseudovirus neutralisation assays. AZD8895 and AZD1061 
mAbs have been engineered with triple amino acid substitutions (YTE) in the Fc region to 
prolong the half-life, which is expected to provide protection from COVID-19 for a duration 
of at least 5 months. An additional triple amino acid substitution (TM) in the Fc region was 
engineered for both AZD8895 and AZD1061 to reduce Fc-mediated effector function, which 
is expected to reduce theoretical risk of antibody-dependent enhancement of disease.
A detailed description of the chemistry, pharmacology, efficacy, and safety of AZD7442 is 
provided in the Investigator’s Brochure.
2.3
Benefit/Risk Assessment
More detailed information about the known and expected benefits and potential risks of 
AZD7442 may be found in the Investigator’s Brochure.
CCI


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2.3.1
Risk Assessment
There are no identified risks associated with AZD7442. No observations are considered to 
represent expected adverse reactions that would form part of an emerging safety profile.
As of the data cut-off date of 27 November 2020 (Investigator’s Brochure edition 4.0), a total 
of 60 healthy adult participants from the UK had been randomised into 5 cohorts and received 
a single dose of AZD7442 (10 participants per cohort) or placebo (2 participants per cohort) in 
the FTIH Phase I dose-escalation study (D8850C00001): 300 mg IM (mAbs administered as 
separate injections), 300 mg IV, 1000 mg IV, and 3000 mg IV (mAbs administered as separate 
infusions), and 3000 mg IV (mAbs co-administered in a single infusion).
#
There were no deaths, SAEs, or discontinuations of the study intervention due to AEs in 
any participant.
#
All AEs reported were mild in intensity, with the exception of the following events of 
moderate intensity: urinary tract infection (1 participant; 300 mg IM); headache and 
malaise (1 participant each; 300 mg IV), dysmenorrhea, headache, and toothache 
(1 participant each; 1000 mg IV), headache, back pain, and arthralgia (1 participant each; 
3000 mg IV).
#
There were no haematology, clinical chemistry, or vital signs findings of concern in any 
participant.
#
No safety signals in this healthy adult population were observed. These results 
demonstrated an acceptable safety profile for AZD7442, including no observed 
infusion-related reactions (IV cohorts), injection site reactions (IM cohort), or 
hypersensitivity reactions, and support the use of AZD7442 in further clinical studies.
AZD7442 is a combination of 2 human mAbs, with distinct binding sites, directed against 
RBD of the SARS-CoV-2 S protein for neutralisation of the virus. Neither mAb has any 
human target. There are no potential risks based on the mechanism of action.
Potential risks are associated with the administration of any Ig, including polyclonal Ig 
preparations and mAbs.
The important potential risks associated with the administration of Ig, include, but are not 
limited to, anaphylaxis and other serious hypersensitivity reactions including immune 
complex disease.
Other potential risks include, but are not limited to, injection site reactions, infusion-related 
reactions, and ADE disease.
Antibody-dependent enhancement of disease is a theoretical risk. Two different syndromes 


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exist:
#
ADE, which involves increased binding efficiency of virus-antibody complexes to Fc 
receptor bearing cells and which triggers virus entry. The mAbs in AZD7442 have been 
designed with a modification to prevent binding to cellular Fc receptors, so the risk of 
ADE occurring via this mechanism should range from very low to none.
#
Vaccine-associated enhanced respiratory disease, which is a distinct clinical syndrome 
that occurred in young children in the 1960s when whole inactivated virus vaccines for 
measles and RSV were tested.
Immunising with limiting doses of RSV antigen, especially with conformationally incorrect 
antigens, can result in 2 major types of immunological phenomena:
#
A relatively high ratio of antibody that binds, but does not neutralise, the virus could 
potentially result in immunogenic cell death and complement activation (leading to 
inflammation and airway obstruction)
#
Immunisation with whole inactivated virus vaccines can result in allergic inflammation 
characterised by, eg, increased mucus production, airway hyperresponsiveness, and 
attenuated cytolytic T cell activity (T helper 2 cell immune response). This mechanism, 
induced by vaccines, should not be provoked by mAbs.
2.3.2 Benefit Assessment
Recipients of AZD7442 do not have any guaranteed benefit; however, AZD7442 may be 
efficacious and offer participants protection from COVID-19.
In the STORM CHASER trial in adults who had been potentially exposed to a SARS-CoV-2 
positive individual, AZD7442 reduced the risk of developing symptomatic COVID-19 by 33% 
(95% CI: -26, 65) compared to placebo, which was not statistically significant. In a pre-
planned analysis of SARS-CoV-2 PCR positive (detectable virus) and PCR negative (no 
detectable virus) participants, AZD7442 reduced the risk of developing symptomatic COVID-
19 by 73% (95% CI: 27, 90) compared with placebo, in participants who were PCR negative 
at time of dosing (AstraZeneca 2021a).
In the PROVENT pre-exposure prophylaxis trial in adults who have increased risk for 
inadequate response to active immunisation (predicted poor responders to vaccines or 
intolerant of vaccine) or having increased risk for SARS-CoV-2 infection, AZD7442 reduced 
the risk of developing symptomatic COVID-19 by 77% (95% CI: 46, 90), compared to 
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2.3.3 Overall Benefit: Risk Conclusion
Taking into account the measures taken to minimise risk to participants in this study, the 
potential risks identified in association with AZD7442 are justified by the anticipated benefits 
that may be afforded to participants at risk of COVID-19.


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3
OBJECTIVES AND ENDPOINTS
The objectives and endpoints for the study are presented in Table 3.
Table 3
Objectives and Endpoints
Objectives
Endpoints
Primary
•
To evaluate the safety and tolerability of a 
single dose of 600 mg AZD7442 administered 
IV to Chinese participants (including those with 
stable medical conditions) ≥
 of age at 
6 months after administration
•
AEs, SAEs, AESIs, safety laboratory parameters 
(haematology, clinical chemistry, coagulation, 
and urinalysis); 12-lead ECG; vital signs (blood 
pressure, pulse rate, body temperature, and 
respiratory rate)
Secondary
•
To evaluate the safety and tolerability of a 
single dose of 600 mg AZD7442 administered 
IV to Chinese participants (including those with 
stable medical conditions) ≥
 of age at 
15 months after administration
•
AEs, SAEs, AESIs, safety laboratory parameters 
(haematology, clinical chemistry, coagulation, 
and urinalysis); 12-lead ECG; vital signs (blood 
pressure, pulse rate, body temperature, and 
respiratory rate)
•
To evaluate the serum PK of AZD8895 and 
AZD1061 after a single dose of 600 mg 
AZD7442 administered IV
Where possible, PK parameters will be assessed for 
individual mAbs (AZD8895 and AZD1061):
•
Cmax, AUC(0-180days)
•
Additional PK parameters that may be 
determined when appropriate include:
!
AUClast, AUCinf, t½λz, tlast, Vss, Vz, and 
CL
•
To evaluate the ADA responses to AZD7442 in 
serum
•
Presence of ADA to AZD8895 and AZD1061 in 
serum
Blood samples will be collected and stored for 
analysis of ADAs. Unscheduled samples for ADA 
analysis may be collected in response to suspected 
immune-related AEs.
Exploratory a
•
 
•
 
•
 
 
•
 
•
 
 
 
•
 
 
•
 
a
Results may be reported separately from the clinical study report.
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ADA, antidrug antibody; AE, adverse event; AESI, adverse event of special interest; AUC(0-180days), area 
under the concentration-time curve from time zero to 180 days; AUCinf, area under the concentration-time curve 
from time zero to infinity; AUClast, area under the concentration-time curve from time zero to time of last 
measurable concentration; CL, clearance; COVID-19, coronavirus disease 2019; Cmax, maximum concentration; 
ECG, electrocardiogram; IV, intravenous; mAb, monoclonal antibody; PK, pharmacokinetics; 
qRT-PCR, quantitative reverse transcriptase polymerase chain reaction; SAE, serious adverse event; 
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; t½λz, terminal elimination half-life, estimated as 
(ln2)/∀z; tlast, time of last quantifiable concentration; Vss, volume of distribution at steady state; Vz, volume of 
distribution based on terminal phase.
4
STUDY DESIGN
4.1
Overall Design
This is a Phase II, randomised, double-blind, placebo-controlled study to evaluate the safety, 
tolerability, PK, and PD of AZD7442 in Chinese adult participants ≥
 of age, 
including healthy participants as well as participants with stable medical conditions. The study 
will be conducted in clinical study centres in mainland China.
The study is expected to be approximately 479 days in duration for each participant, 
consisting of a screening period of up to 28 days (Days -28 through -1), an intervention period 
of one day (Day 1 [randomisation and dosing]), and a safety follow-up period of 450 days 
(Days 2 through 451). The overall study design is presented in Figure 1. The study flow chart 
is presented in Figure 2.
Approximately 272 participants who fulfil the study eligibility criteria (Sections 5.1 and 5.2) 
will be randomised in a 3:1 ratio to receive a single dose of study intervention administered 
IV, either 600 mg AZD7442 (204 participants) or placebo (68 participants). Randomisation 
will be stratified by
 
at screening. Considering the increased vaccination roll-out in 
China, non-vaccinated participants are expected to be no more than 35% of the study 
population.
The study intervention will be co-administered as a single IV infusion containing both mAbs 
(AZD8895 and AZD1061)/placebo (see Sections 6.1.1 and 6.2 for additional details). 
Participants will then be monitored for approximately 15 months after dosing (through 
Day 451) for safety, including the recording of AEs, AESIs, and SAEs, and the collection of 
blood samples for PK, PD, and ADAs.
There will be 2 DBLs during the study (see Section 9 for additional details):
#
The primary DBL will occur after all treated participants have completed follow-up 
through Day 181 for the primary analysis.
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#
The final DBL will occur after all treated participants have completed the study, ie, have 
completed follow-up through Day 451 for the final analysis.
As no multiplicity control is applied, ad-hoc interim analyses may be performed, if warranted, 
for additional evaluation of a potential signal in the safety profile.
As the study will very likely take place during the COVID-19 pandemic, measures will be put 
in place to ensure minimal SARS-CoV-2 exposure for site staff as well as study participants. 
Exclusion and withdrawal criteria are in place to ensure site staff and study participant safety, 
and participants will be monitored for COVID-19 symptoms during the study and tested for 
SARS-CoV-2 if warranted based on the investigator’s judgment. SARS-CoV-2 positive results 
during the study will be reported as AEs and measures will be applied at the discretion of the 
investigator to minimise further SARS-CoV-2 exposure as much as possible. SARS-CoV-2 
infection (based on qRT-PCR and serology) will also be assessed as exploratory endpoints 
(Section 8.1).
4.2
Scientific Rationale for Study Design
This is a Phase II, randomised, double-blind, placebo-controlled study. Randomisation and 
blinding will minimise potential bias.
The potential target population for the development of AZD7442 is the general population and 
specifically healthcare workers, or individuals at increased risk of COVID-19 or those who 
are expected to have a severe outcome and need immediate protection. In this Phase II study, 
Chinese participants from mainland China ≥
 of age who are healthy or who have 
stable medical conditions (eg, those who could potentially have an impaired response to a 
vaccine such as participants with immunosuppression) will be included. As older participants 
are considered to be at increased risk for inadequate response to active immunisation on the 
basis of age (immunosenescence), randomisation will be stratified by 
 
. Furthermore, considering the increased COVID-19 vaccination roll-out in China, 
vaccinated participants will be eligible for the study and are expected to comprise a majority 
of participants (non-vaccinated participants are expected to be no more than 35% of the study 
population). According to China Guideline for Clinical Evaluation of COVID-19 Vaccines 
(Draft), 6 months protection should be provided (NMPA 2020). Therefore, for eligibility in the 
study, a minimum interval of 6 months between receipt of the COVID-19 vaccine and dosing 
with AZD7442 is considered adequate to minimise potential complication/interference in 
PK/PD and safety evaluation of AZD7442. 
 
 at screening to ensure 3:1 balanced representation of the 
2 treatment arms in each of the strata. This Phase II study will provide additional safety and 
tolerability data as well as PK and PD data in the Chinese population.
The primary study endpoints are standard endpoints for safety assessment, including AEs, 
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SAEs, and safety clinical laboratory measurements. The secondary study endpoints are those 
required to characterise the PK and ADAs through 360 days after administration (Day 1 
through Day 361). The 15-month follow-up period will allow for follow-up of dosed 
participants through approximately 5 half-lives, which is expected to provide sufficient safety 
follow-up. Collection of blood samples for ADA through Day 361 will also maximise the 
probability of detecting ADA to AZD7442. The PK endpoints will describe the disposition of 
AZD7442 in participants after IV administration. Antidrug antibody responses will be 
measured to ensure that they are at acceptable levels and do not affect safety or PK. T
 
 
 however, based on the limited sample size and 
current COVID-19 status in China, no trend in occurrence of infection is expected to be 
observed.
4.3
Justification for Dose
This study will be conducted with a 600 mg IV dose of AZD7442. This is the highest dose that 
is to be evaluated in the planned Phase I study (D8850C00007) in healthy Chinese 
participants. As the primary objective of the Phase II study is to evaluate the safety of 
AZD7442, the 600 mg IV dose will have the highest exposure. Additionally, based on the 
linear PK assumption, 600 mg IV is expected to have a higher exposure and can provide 
efficacy that is not less than 300 mg IV or 600 mg IM in the treatment of SARS-CoV-2 
infection.
The dose regimens 300 mg IM and 300, 1000, and 3000 mg IV have been evaluated in the 
ongoing FTIH study (D8850C00001). Tolerability has been confirmed for the dose range from 
300 mg IM to 3000 mg IV. The NOAELs of 600 mg/kg IV or 150 mg/kg IM single dose were 
well tolerated in the cynomolgus monkey toxicity study. The safety margin (monkey/human) 
between 300 mg IM dose in the FTIH study and NOAEL 150 mg/kg IM is 33-fold and 62-fold 
for AUC(0-60days) and Cmax, respectively. When comparing between the clinical 300 mg IV 
dose in the FTIH study and the NOAEL of 600 mg/kg IV dose, a much larger exposure safety 
margin (monkey/human) was obtained, that being 67-fold and 150-fold for AUC(0-60days) 
and Cmax, respectively. For the clinical dose of 1000 mg IV, the safety margin 
(monkey/human) is 22-fold and 49-fold for AUC(0-60days) and Cmax, respectively. For the 
highest 3000 mg IV dose tested in the FTIH study, the safety margin (monkey/human) is 7.5-
fold and 16-fold for AUC(0-60days) and Cmax, respectively. The FTIH study revealed that 
Cmax and partial AUC increased linearly in the dose range between 300 mg to 3000 mg IV 
and the bioavailability of 300 mg IM of AZD7442 (based on the 271-day AUC) was 68.54% 
and 65.79% for AZD8895 and AZD1061, respectively. Based on this information, the 600 mg 
IV dose in humans is expected to be safe since a sufficient exposure margin has covered this 
dose.
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Human efficacious doses were projected based on in vitro functional potency data that account 
for potential synergistic effect of the two-mAb combination. The AZD7442 dose levels of 
300 mg IM, 300 mg IV, 1000 mg IV and 3000 mg IV that are tested in the FTIH study ensure 
exposure in serum and in the ELF of the lungs to be above the IC80 of 40 ng/mL for a duration 
of at least 5 months post-dose.
To further support the selection of the study doses, a viral dynamic model was developed, 
which allows understanding of the PD effects of AZD7442 on the replication of SARS-CoV-2 
and the resulting immune response (Gonçalves et al 2020, Goyal et al 2020, Kim KS et al 
2020, Kim SE et al 2020, Liu et al 2020). The viral dynamic model indicates that virus entry 
inhibition greater than approximately 80% is sufficient to prevent infection. Assuming a 
partition ratio of 1% for lung ELF-to-serum and an IC80 of 40 ng/mL, a 300 mg IM dose 
would provide prophylactic coverage for 6 to 9 months, and this dose and higher doses would 
also be effective to treat active SARS-CoV-2 infection with a significant reduction in peak 
viral load and complete suppression of the viral load earlier than accomplished by the innate 
and acquired immune response only. 
Considering the demonstrated safety in the FTIH study and the predicted efficacy, the dose 
level of 600 mg IV AZD7442 is expected to show good safety and efficacy profiles in the 
Chinese population and have the potential to be applied in clinics.
4.4
End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study including the last scheduled procedure shown in the SoA (Section 1.3).
The end of the study is defined as the date of the last scheduled procedure shown in the SoA 
(Section 1.3) for the last participant in the study.
5
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known 
as protocol waivers or exemptions, is not permitted.
5.1
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1
Chinese adults ≥
 of age, at the time of signing the informed consent.
Informed Consent
2
Capable of giving signed informed consent as described in Appendix A, which includes 
compliance with the requirements and restrictions listed in the ICF and in this protocol.
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Type of Participant and Disease Characteristics
3
Healthy participants or participants with stable medical conditions.
(a) Participants who are healthy by medical history, physical examination, and baseline 
safety laboratory tests, as judged by the investigator.
OR
(b) Participants with stable disease/condition, as judged by the investigator, who may 
benefit from passive immunisation with antibodies. “Stable” is defined below as:
o
No hospitalisation or emergency visit for worsening of disease/condition within 
the 12 months prior to enrolment.
o
No acute change in the participant’s condition at the time of study enrolment, 
and, as judged by the investigator, no exacerbation in disease/condition and no 
significant change in therapy expected during at least the first 6 months of the 
study.
o
Participation in the clinical study not expected to pose a significant risk to the 
participant, as judged by the investigator.
o
Diseases/conditions include elderly (≥
 of age), obese (BMI ≥
kg/m2), 
chronic obstructive pulmonary disease, congestive heart failure (NYHA 
classification ≤class II), chronic kidney disease, chronic liver disease, 
immunocompromised state requiring maintenance use of corticosteroids and/or 
other immunosuppressive medicines, intolerant of vaccines, or another disease as 
judged by the investigator.
4
Negative results of SARS-CoV-2 qRT-PCR test within 14 days prior to randomisation. 
NOTE: A negative SARS-CoV-2 qRT-PCR retest result is required if participant has 
symptoms of infection or has any known/suspected exposure after the initial test.
5
Able to complete the follow-up period through Day 451 as required by the CSP.
Reproduction
Contraceptive use by men or women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.
6
Contraceptive use by men or women:
(a) Male participants: To avoid transfer of fluids to a sexual partner, all male participants 
must use a condom from Day 1 and agree to continue through 365 days following 
administration of the study intervention.
(b) Female participants: Female participants of childbearing potential must use one 
highly effective form of birth control. Women of childbearing potential who are 
sexually active with a non-sterilised male partner must agree to use one highly 
effective method of birth control, as defined below, from Day 1 and agree to continue 
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through 365 days following administration of the study intervention. Cessation of 
contraception after this point should be discussed with a responsible physician. 
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal 
(coitus interruptus), spermicides only, and lactational amenorrhea method are not 
acceptable methods of contraception. Female condom and male condom should not 
be used together. All women of childbearing potential must have a negative serum 
pregnancy test result at Visit 1 and throughout the study as indicated per the SoA 
(Section 1.3).
o
Women not of childbearing potential are defined as women who are either 
permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy), or who are postmenopausal. Women will be considered 
postmenopausal if they have been amenorrhoeic for 12 months prior to the 
planned date of randomisation without an alternative medical cause. The 
following age-specific requirements apply:
∃
Women <
 of age would be considered postmenopausal if they have 
been amenorrhoeic for 12 months or more following cessation of exogenous 
hormonal treatment and follicle stimulating hormone levels in the 
postmenopausal range.
∃
Women ≥
 of age would be considered postmenopausal if they have 
been amenorrhoeic for 12 months or more following cessation of all 
exogenous hormonal treatment.
o
A highly effective method of contraception is defined as one that can achieve a 
failure rate of less than 1% per year when used consistently and correctly. 
Examples of highly effective birth control methods are listed in Table 4.
Table 4
Highly Effective Methods of Contraception
Barrier method
Hormonal method
•
Intrauterine device
•
Intrauterine hormone-releasing system a
•
Bilateral tubal occlusion
•
Vasectomised partner b
•
Sexual abstinence c
•
Combined (estrogen- and progestogen-
containing hormonal contraception) associated 
with inhibition of ovulation
!
Oral (combined pill)
!
Intravaginal
!
Injectable
!
Transdermal (patch)
•
Progestogen-only hormonal contraception 
associated with inhibition of ovulation
!
Oral
!
Injectable
!
Implantable
a
This is also considered a hormonal method.
b
Provided that partner is the sole sexual partner of the woman of childbearing potential study participant and 
that the vasectomised partner has received medical assessment of the surgical success.
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c
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of the study and if it is the preferred and usual lifestyle of the 
participant.
5.2
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1
Known history of allergy or reaction to any component of the study intervention 
formulation.
2
Previous hypersensitivity, infusion-related reactions, or severe adverse reaction following 
administration of an mAb.
3
Significant infection or other acute illness, including fever > 100 °F (> 37.8 °C) on the 
day prior to or day of randomisation. Participants excluded for transient acute illness may 
be dosed if illness resolves within the 28-day screening period. Otherwise, the participant 
will be reported as a screen failure. Upon obtaining an informed consent again, the 
participant may be rescreened just once (Section 5.4).
4
History of infection with severe acute respiratory syndrome (SARS) or Middle East 
respiratory syndrome (MERS).
5
History of laboratory-confirmed SARS-CoV-2 infection. NOTE: Participants with any 
positive SARS-CoV-2 qRT-PCR result based on available data at screening will be 
excluded. Non-vaccinated participants with any positive SARS-CoV-2 serology result 
based on available data at screening will be excluded.
6
Any clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, 
dyspnoea, sore throat, fatigue, or confirmed infection by appropriate laboratory test 
within the last 4 weeks prior to screening or randomisation.
7
History of malignancy.
(a) Participants who have had basal cell carcinoma, localized squamous cell carcinoma 
of the skin, or in situ carcinoma of the cervix are eligible provided that the participant 
is in remission and curative therapy was completed at least 12 months prior to 
enrolment.
(b) Participants who have had other malignancies are eligible provided that the 
participant is in remission and curative therapy was completed at least 5 years prior 
to enrolment.
8
History of clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or 
platelet disorder), or prior history of significant bleeding or bruising following IM 
injections or venepuncture.
9
Current active liver disease.
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or hepatitis C antibody), or other stable chronic liver disease are acceptable if the 
participant otherwise meets eligibility criteria. Stable chronic liver disease should 
generally be defined by the absence of ascites, encephalopathy, coagulopathy, 
hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis.
10 History of HIV or positive HIV at screening.
11 History of alcohol or drug abuse within the past 2 years that, according to the investigator, 
might affect assessments of safety or ability of the participant to comply with all study 
requirements.
12 Any other significant disease, disorder, or finding that may significantly increase the risk 
to the participant because of participation in the study, affect the ability of the participant 
to participate in the study, or impair interpretation of the study data.
Significant Laboratory Abnormalities
13 Any of the following laboratory abnormalities at screening:
(a) AST or ALT > 2.0 × ULN, ALP > 1.5 × ULN, or TBL > 1.5 × ULN (unless due to 
Gilbert’s syndrome)
(b) Serum creatinine > 176 μmol/L (2 mg/dL)
(c) Haemoglobin < 10 g/dL (100 g/L)
(d) Platelet count < 100 × 103/μL (100 × 109/L)
(e) White blood cell count < 3.5 × 103/μL (3.5 × 109/L) or neutrophil count 
< 1.5 × 103/μL (1.5×109/L)
(f) Any other laboratory value in the screening panel that, in the opinion of the 
investigator, is clinically significant or might confound analysis of study results
Prior/Concomitant Therapy
14 Any newly initiated drug therapy within 7 days or 5 drug half-lives (whichever is longer) 
prior to screening.
15 Receipt of Ig or blood products within 6 months prior to screening.
16 Any prior receipt of an investigational or licensed mAb/biologic indicated for the 
prevention of SARS-CoV-2 or COVID-19 or scheduled to receive any investigational or 
licensed mAb/biologic indicated for the prevention of SARS-CoV-2 or COVID-19.
17 Receipt of any COVID-19 vaccine within 6 months prior to randomisation or scheduled 
to receive any COVID-19 vaccine.
Prior/Concurrent Clinical Study Experience
18 Receipt of any investigational product within 90 days or 5 antibody half-lives (whichever 
is longer) prior to Day 1, or expected receipt of investigational product during the 
follow-up period, or concurrent participation in another interventional study.


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Other Exclusions
19 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca 
staff and/or staff at the study site).
20 Judgment by the investigator that the participant should not participate in the study if the 
participant is unlikely to comply with study procedures, restrictions, and requirements.
21 For women only - currently pregnant (confirmed with positive pregnancy test) or 
breastfeeding.
5.3
Lifestyle Considerations
#
Restrictions relating to concomitant medications are described in Section 6.5.
#
Participants must abstain from donating blood or plasma from the time of informed 
consent and for 5 half-lives after dose of study intervention; ie, 15 months.
5.3.1
Meals and Dietary Restrictions
#
There are no meal and dietary restrictions.
5.3.2
Caffeine, Alcohol, and Tobacco
#
There are no caffeine, alcohol, and tobacco restrictions.
5.3.3
Activity
#
Participants should rest comfortably during the IV infusion and for 1 hour after the end of 
the infusion.
#
Participants should abstain from strenuous activity for 72 hours prior to dosing and 
24 hours after dosing.
5.3.4
Reproduction/Contraception Requirements
Male Participants:
#
To avoid transfer of fluids to a sexual partner, all male participants must use a condom 
starting from Day 1 and through 365 days following administration of the study 
intervention (Section 5.1).
#
Male participants should refrain from fathering a child during the study and for 365 days 
following the administration of study intervention. Contraception for female partners of 
childbearing may be considered, but is not required for this protocol.
#
Male participants should not donate sperm from Day 1 and through 365 days following 
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Female Participants:
#
Female participants must follow the contraception requirements outlined in Section 5.1.
#
Female participants must abstain from breastfeeding during the study.
#
Female participants should not donate ova from Day 1 and through 365 days following 
administration of the study intervention.
5.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet 
the Consolidated Standards of Reporting Trials publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen failure 
details, eligibility criteria, and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened if the eligibility criterion that resulted in screen failure has changed in a manner 
that meets eligibility. Only a single rescreening is allowed in the study. Rescreened 
participants should be assigned the same participant number as for the initial screening 
(Appendix A 3).
6
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), or 
placebo intended to be administered to a study participant according to the study protocol.


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6.1
Study Intervention(s) Administered
6.1.1
Investigational Products
The study intervention (AZD7442 and placebo) is described in Table 5.
Table 5
Investigational Medicinal Products
Intervention name
AZD7442 (AZD8895 + AZD1061)
Placebo
Type
Biological
Drug
Dose formulation
AZD7442 is comprised of the 2 mAbs, 
and will be supplied as separate vials of 
AZD8895 and AZD1061 as sterile, 
clear to opalescent, colourless to yellow 
solutions. The solutions contain 
100 mg/mL of active ingredient 
(AZD8895 or AZD1061) in 20 mM 
L-histidine /L-histidine hydrochloride,
240 mM sucrose, and 0.04% (w/v) 
polysorbate 80, at pH 6.0. The 
label-claim volume is 1.5 mL and each 
vial contains 150 mg (nominal) of 
active ingredient.
Sterile solution of 0.9% (w/v) sodium 
chloride for injection
Unit dose strength(s)
150 mg (nominal) AZD8895 or 
AZD1061 per vial
Not applicable
Dosage level(s)
AZD7442 doses (combined doses of 
AZD8895 and AZD1061) to be 
administered:
600 mg IV co-administration (300 mg 
AZD8895 and 300 mg AZD1061)
Dosing to match AZD7442 (AZD8895 
and AZD1061)
Route of administration
IV infusion
IV infusion
Use
Experimental
Placebo
Sourcing
Provided centrally by the sponsor
Provided locally by the study site or by 
the sponsor
Packaging and labelling
Each vial will be labelled in accordance 
with GMP Annex 13 and per regulatory 
requirement in China.
0.9% (w/v) sodium chloride for 
injection sourced by the study site or by 
the sponsor.
GMP, Good Manufacturing Practice; w/v, weight per volume; IV, intravenous; mAb, monoclonal antibody.
6.2
Preparation/Handling/Storage/Accountability
6.2.1
Storage and Accountability
1
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention.


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2
Only participants randomised in the study may receive study intervention and only 
authorised site staff may supply or administer study intervention. All study intervention 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labelled storage conditions with access limited to 
the investigator and authorised site staff.
3
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).
4
Further guidance and information for the final disposition of unused study interventions 
are provided in the Investigational Medicinal Product Manual or other equivalent 
documents.
6.2.2
Preparation and Administration
All products must be stored at 2 °C to 8 °C and used within the assigned expiry date on the 
label.
The dose of AZD7442 for administration must be prepared using aseptic technique. The total 
time from needle puncture of the vial to the start of administration must not exceed:
#
24 hours at 2 °C to 8 °C
#
4 hours at room temperature
If the final product is stored at both refrigerated and room temperatures, the total time must 
not exceed 24 hours; otherwise, a new dose must be prepared using new vials.
The study intervention does not contain preservatives and any unused portion must be 
discarded.
Use a single 50 to 100 mL 0.9% (w/v) sodium chloride IV bag for both AZD8895 and 
AZD1061 infusion and placebo infusion. Use a soft IV bag made of polyolefin (PO), 
polyvinylchloride (PVC), or polyethylene (PE).
Steps 1, 2, and 3 will be performed by an unblinded qualified professional:
Step 1:
Retrieval of AZD7442 vials or placebo
(a) For AZD7442, remove the required number of vials (AZD8895 and AZD1061) for 
administration, as shown below in Table 6.


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Table 6
Required Vials of AZD7442 (AZD8895 and AZD1061)
Dose level
Number of 
required 
AZD8895 vials
Volume of 
AZD8895
Number of 
required 
AZD1061 vials
Volume of 
AZD1061
600 mg AZD7442 
(300 mg AZD8895 
and 300 mg 
AZD1061)
2
3 mL
2
3 mL
(b) For placebo, remove the 0.9% (w/v) sodium chloride solution from storage.
Step 2:
Accurately withdraw the required volume for the infusion and add to the IV bag as required 
(see below):
(a) AZD7442: Remove 3 mL of AZD8895 from 2 AZD8895 vials and transfer to an IV 
bag. Then, remove 3 mL of AZD1061 from 2 AZD1061 vials and transfer to the 
same IV bag. Mix the bag by gently inverting to ensure homogeneity of the dose in 
the bag.
(b) Placebo: Remove 6 mL of 0.9% (w/v) sodium chloride and transfer to an IV bag.
Step 3:
Use a coloured shading bag or attach labels and cover to the IV bags in order to ensure 
blinding.
A blinded qualified professional must perform Steps 4 and 5:
Step 4:
Administer the entire contents of the IV bag using IV administration sets containing low 
protein binding 0.2-μm or 0.22-μm filters made of polyethersulfone (PES). The target infusion 
time is 30 minutes and the target infusion rate is 20 mg/minute, which translates to IV pump 
programmable rates of approximately:
#
100 mL/hr for a 50 mL IV bag
#
200 mL/hr for a 100 mL IV bag
Step 5:
Flush the IV line according to local practices to ensure the full dose is administered. Infusion 
time does not include the final flush time. Flush the catheter with 0.9% (w/v) sodium chloride 


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at the end of the infusion.
6.3
Measures to Minimise Bias: Randomisation and Blinding
All participants who fulfil eligibility criteria will be centrally assigned to randomised study 
intervention using an IRT/RTSM. Before the study is initiated, the log-in information and 
directions for the IRT/RTSM will be provided to each site. Refer to the IRT/RTSM user 
manual that will be provided to each centre.
Randomisation will be stratified by 
 
 at screening. Considering the increased 
vaccination roll-out in China, non-vaccinated participants are expected to be no more than 
35% of the study population.
If a participant withdraws from the study, then his/her enrolment/randomisation code cannot 
be reused. Withdrawn participants will not be replaced.
Investigators and participants will remain blinded to each assigned study intervention 
throughout the course of the study. To maintain blinding, the IRT/RTSM will provide to the 
unblinded pharmacists the kit identification number to be allocated to the participant at the 
dispensing visit.
Unblinded site personnel will endeavor to ensure that there are no differences in time taken to 
dispense following randomisation. Unblinded site personnel also will be instructed to avoid 
discussing the colour, or packaging of the study intervention with investigators and the 
participant (or legally authorised representative).
Code break services provided by IRT/RTSM will be available to the investigator and Patient
Safety department at AstraZeneca for individual blind breaking.
The randomisation code should not be broken except in medical emergencies when the 
appropriate management of the participant requires knowledge of the treatment randomisation. 
The investigator documents and reports the action to AstraZeneca, without revealing the study 
intervention given to the participant to the AstraZeneca staff.
AstraZeneca retains the right to break the code for SAEs that are unexpected and are 
suspected to be causally related to a study intervention and that potentially require expedited 
reporting to regulatory authorities. Randomisation codes will not be broken for the planned 
analyses of data until all decisions on the evaluability of the data from each individual 
participant have been made and documented.
The IRT/RTSM will be programmed with blind-breaking instructions. In case of an 
emergency, in which the knowledge of the specific blinded study intervention will affect the 
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immediate management of the participant’s condition (eg, antidote available), the investigator 
has the sole responsibility for determining if unblinding of a participant’s intervention 
assignment is warranted. Participant safety must always be the first consideration in making 
such a determination. If a participant’s intervention assignment is unblinded, the sponsor must 
be notified within 24 hours after breaking the blind.
6.4
Study Intervention Compliance
Participants will be dosed at the site and will receive study intervention directly from the 
investigator or designee, under medical supervision. The date, and time if applicable, of the 
dose administered in the clinic will be recorded in the source documents and recorded in the 
eCRF. The dose of study intervention and study participant identification will be confirmed at 
the time of dosing by a member of the study site staff other than the person administering the 
study intervention.
6.5
Concomitant Therapy
Any medication or vaccine (including OTC or prescription medicines, vitamins, and/or herbal 
supplements) that the participant is receiving at the time of enrolment or receives during the 
study must be recorded along with:
#
Reason for use
#
Dates of administration including start and end dates
#
Dosage information including dose and frequency
The study physician should be contacted if there are any questions regarding concomitant or 
prior therapy.
Participants may take concomitant medications prescribed by their primary care provider for 
management of chronic medical conditions and/or for health maintenance. Primary care 
providers or, where appropriate investigators, should prescribe appropriate concomitant 
medications or treatments deemed necessary to provide full supportive care and comfort 
during the study.
Permitted, restricted, and prohibited medications are summarised in Table 7.


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Table 7
Summary of Medications and Treatments Permitted, Prohibited, and 
Restricted During the Study
Use category
Type of medication/treatment
Timeline/instructions
Permitted
Contraceptives or a single use of 
acetaminophen, aspirin, antihistamine, or 
combination OTC product that contains 
acetaminophen with an antihistamine, or 
OTC nonsteroidal anti-inflammatory agent
At a dose equal to or lower than that 
recommended on the package (at the 
discretion of the investigator)
Vitamins and other nutritional supplements
Not newly introduced, ie, have been taken 
for at least 30 days prior to screening
Prohibited
Not applicable
Not applicable
Restricted
COVID-19 vaccines
See Section 6.5.1 for details
Any other drug therapy
Newly initiated drugs within 7 days or 
5 half-lives (whichever is longer) prior to 
screening is not allowed until the 
completion of the study, unless, in the 
opinion of the investigator, the medication 
will not interfere with the study. Note: 
participants with stable chronic conditions 
may continue taking their maintenance 
medications provided they have taken them 
for at least 30 days prior to screening and at 
a stable dose for at least 7 days or 
5 half-lives (whichever is longer).
COVID-19, coronavirus disease 2019; OTC, over-the-counter.
6.5.1
COVID-19 Vaccines
#
When a participant becomes eligible for the nationally deployed COVID-19 vaccine and 
it is locally available, they will be able to be unblinded on request, after a fully informed, 
objective discussion based on all available up-to-date information, and remain in the 
study.
%
Unblinded participants who received placebo should be advised that no 
study-associated contraindication to receiving a vaccine exists.
%
Unblinded participants who received AZD7442 should be advised that the 600 mg 
dose may provide 6 to 9 months of protection, but that this has not yet been 
demonstrated. In these participants, there would be little or no urgency for receiving a 
vaccine. In addition, in the presence of adequate neutralising antibody titres, an 
appropriate and effective response to the vaccine could be impaired. Such 
participants should be advised to consider waiting an appropriate length of time (as 
suggested above for the dose) before receiving an anti-SARS-CoV-2 vaccine. For 
AZD7442, the number of months identified above for the dose represents the 
approximate number of elimination half-lives of the mAbs, after which the potential 


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for the mAbs to protect against COVID-19 should be reduced, and after which their 
potential interference with a vaccine may be reduced.
#
For participants who have received study intervention (blinded) and develop symptomatic 
COVID-19 at some point in the study:
%
There is no reason to believe that administration of a vaccine during acute COVID-19 
will ameliorate the illness.
%
In almost all placebo recipients, and in most mAb recipients, an infection-induced 
immune response will occur, and this response should be protective. At this time, 
there is no reason to believe that the protection afforded by natural infection is less 
frequent or less robust than the protection provided by a vaccine, so the benefit of 
vaccination may be limited.
%
The risk of receiving a vaccine after resolution of the illness should be low.
6.6
Dose Modification
The study intervention will be administered as described in Sections 6.1.1 and 6.2.2. Dose 
modification is not permitted. Re-administration of a dose is not permitted.
6.7
Intervention After the End of the Study
There is no intervention after the end of the study (see definition in Section 4.4).
7
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
At any time, participants are free to discontinue study intervention or withdraw from the 
study, without prejudice to further treatment.
7.1
Discontinuation of Study Intervention
Each participant randomised in this study will receive a single dose of study intervention on 
Day 1 as detailed in Sections 6.1.1 and 6.2.2.
If the infusion of study intervention is interrupted and not resumed (ie, it is discontinued), the 
participant should remain in the study to be evaluated for the full study period (up to and 
including Day 451, 450 days after study intervention dosing) with all laboratory and clinical 
evaluations collected as defined in this CSP, unless the participant withdraws consent to 
participate in the study. Note that discontinuation from study intervention is NOT the same 
thing as a withdrawal from the study. See the SoA (Section 1.3) for data to be collected at the 
time of discontinuation of study intervention and follow-up and for any further evaluations 
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7.2
Participant Withdrawal from the Study
#
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioural, 
compliance, or administrative reasons. This is expected to be uncommon.
#
A participant who considers withdrawing from the study must be informed by the
investigator about modified follow-up options (eg, telephone contact, a contact with a 
relative or treating physician, or information from medical records).
#
At the time of withdrawal from the study, if possible, an early study intervention 
discontinuation visit should be conducted, as shown in the SoA (Section 1.3). See the 
SoA for data to be collected at the time of study withdrawal and follow-up and for any 
further evaluations that need to be completed.
%
The participant will discontinue the study intervention and be withdrawn from the 
study at that time.
#
If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
#
If a participant withdraws from the study, it should be confirmed if he/she still agrees for 
existing samples to be used in line with the original consent. If he/she requests withdrawal 
of consent for use of samples, destruction of any samples taken and not tested should be 
carried out in line with what was stated in the informed consent and local regulation. The 
investigator must document the decision on use of existing samples in the site study 
records and inform the Global Study Team.
7.3
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
#
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study.
#
Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record.


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#
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix A.
8
STUDY ASSESSMENTS AND PROCEDURES
#
Study procedures and their timing are summarised in the SoA (Section 1.3). Protocol
waivers or exemptions are not allowed.
%
Unscheduled Visits: An unscheduled visit may occur in-between scheduled visits, eg, 
to follow up on potential safety events.
#
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention.
#
Adherence to the study design requirements, including those specified in the SoA
(Section 1.3), is essential and required for study conduct.
#
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
#
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICF may be utilised for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA (Section 1.3).
8.1
Efficacy Assessments
8.1.1
will be performed as specified in 
the SoA (Section 1.3). Additionally, a participant should be instructed to contact the study site 
 
. 
 should be performed at the 
discretion of the investigator. 
 
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Table 8
COVID-19 Qualifying Symptoms
Participant must present with at least one of the following symptoms:
Duration
Symptom
No minimum duration
Fever
Shortness of breath
Difficulty breathing
Must be present for ≥2 days
Chills
Cough
Fatigue
Muscle aches
Body aches
Headache
New loss of taste
New loss of smell
Sore throat
Congestion
Runny nose
Nausea
Vomiting
Diarrhoea
Adapted from US CDC 2021.
COVID-19, coronavirus disease 2019; US CDC, United States Centers for Disease Control and Prevention.
8.1.2
Serum samples will be collected to assess 
 from 
all participants at time points specified in the SoA (Section 1.3) and will be analysed provided 
the analysis method is established and appropriate approval has been obtained. 
 
 in participants receiving AZD7442 versus 
placebo will be
 
 operated by an authorised laboratory.
8.2
Safety Assessments
Planned time points for all safety assessments are provided in the SoA (Section 1.3).
8.2.1
Physical Examinations
Physical examination will be performed at time points specified in the SoA (Section 1.3). For 
AE reporting regarding physical examination, see Section 8.3.6.
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#
A complete physical examination will include assessments of the following: height and 
BMI (screening only); weight; general appearance; respiratory, cardiovascular, abdomen, 
skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, 
muscular-skeletal (including spine and extremities), and neurological systems.
#
A brief physical examination will include, at a minimum, assessments of the general 
appearance, skin, lungs, cardiovascular system, and abdomen (liver and spleen). 
Symptom-directed physical examination should be performed to assess symptoms 
reported by participant.
8.2.2
Vital Signs
Vital signs will be performed at time points specified in the SoA (Section 1.3).
The following variables will be collected after the participant has rested in the supine position 
for at least 5 minutes:
#
Systolic blood pressure (mm Hg)
#
Diastolic blood pressure (mm Hg)
#
Pulse rate (beats per minute)
#
Body temperature
#
Respiratory rate (breaths per minute)
8.2.3
Electrocardiograms
An ECG will be performed at time points specified in the SoA (Section 1.3). A 12-lead ECG 
will be obtained after at least 5 minutes supine rest.
Results for PR interval, QRS duration, QT interval, QTcF interval, RR interval, and heart rate 
will be recorded in eCRF. In addition, the investigators will judge the overall interpretations as 
normal, abnormal together with their reasons, and this evaluation will be reported in eCRF. If 
abnormal, it will be further documented as to whether or not the abnormality is clinically 
significant by the investigators. For all abnormalities (regardless of clinical significance) the 
specific type and nature of the abnormality will be documented in eCRF. Clinically significant 
findings should also be documented on the AE page of the CRF if applicable. 
The investigators may add extra 12-lead resting ECG assessments if there are any abnormal 
findings or if the investigators consider them to be required for any other safety reason. These 
assessments should be entered as unscheduled assessments.
ECG results will be stored at the site with their photocopy dated and signed/sealed by the 
investigators.


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8.2.4
Clinical Safety Laboratory Assessments
Blood and urine samples for determination of clinical chemistry, haematology, urinalysis, 
coagulation, pregnancy testing, viral serology, and SARS-CoV-2 testing will be taken at the 
visits indicated in the SoA (Section 1.3).
Additional safety samples may be collected, if clinically indicated, at the discretion of the 
investigator. The date and time of collection and results (values, units, and reference ranges) 
will be recorded on the appropriate eCRF.
Blood and urine samples for determination of clinical chemistry, haematology, urinalysis, 
coagulation, viral serology, pregnancy testing (serum beta-hCG at screening), and 
reproductive status (serum for FSH at screening) will be performed at a central laboratory. 
Instructions for the collection and handling of the samples will be provided in the 
study-specific Laboratory Manual. If supplies or test kits are not available, the testing may be 
performed at a local laboratory. Urine samples for pregnancy testing (urine hCG) and samples 
for SARS-CoV-2 serology (at screening) and SARS-CoV-2 qRT-PCR will be performed at a 
local laboratory at or near the investigational site. Samples tested locally will be collected and 
handled per routine practice and laboratory methods at the site.
The following laboratory variables will be measured:
#
Haematology, serum clinical chemistry, urinalysis, and coagulation: Table 9
#
Pregnancy testing: Table 10
#
Viral serology: Table 11
#
SARS-CoV-2 testing: Table 12


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Table 9
Haematology, Serum Clinical Chemistry, Urinalysis, and Coagulation
Haematology
White blood cell (WBC) count
Neutrophils absolute count 
Red blood cell (RBC) count
Lymphocytes absolute count 
Haemoglobin (Hb)
Monocytes absolute count 
Haematocrit (HCT)
Eosinophils absolute count 
Mean corpuscular volume (MCV)
Basophils absolute count 
Mean corpuscular haemoglobin (MCH)
Platelets
Mean corpuscular haemoglobin concentration 
(MCHC)
Reticulocytes absolute count 
Serum clinical chemistry
Sodium
C-reactive protein (CRP)
Potassium
Alkaline phosphatase (ALP)
Urea/blood urea nitrogen (BUN)
Alanine aminotransferase (ALT)
Creatinine
Aspartate aminotransferase (AST)
Albumin
Gamma glutamyl transpeptidase (GGT)
Calcium
Total bilirubin
Phosphate
Conjugated bilirubin
Glucose
Creatine kinase
Urinalysis
Glucose
Protein
Blood
Microscopy (if positive for protein or blood): RBC, 
WBC, Casts (cellular, granular, hyaline)
Coagulation
International normalised ratio (INR)
Prothrombin time
Activated partial thrombin time (aPTT)
Note: If a participant shows an AST or ALT ≥3 × upper limit normal (ULN) together with total bilirubin 
≥2 × ULN, refer to Appendix D - Actions required in cases of increases in liver biochemistry and evaluation of 
Hy’s Law, for further instructions.
Table 10
Pregnancy Testing (Females Only)
Pregnancy Test (FOCBP only):
•
Serum β-hCG (screening; central laboratory)
•
Urine hCG (pre- and post-dose; local 
laboratory)
Reproductive status test (suspected postmenopausal 
women < 
 only):
•
FSH (using serum at screening; central 
laboratory)
β-hCG, beta human chorionic gonadotropin; FOCBP, females of childbearing potential; FSH, follicle-stimulating 
hormone; hCG, human chorionic gonadotropin.
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Table 11
Viral Serology Testing
Hepatitis B surface antigen
HIV
Hepatitis C virus antibody
HIV, human immunodeficiency virus.
Table 12
SARS-CoV-2 Testing
SARS-CoV-2 qRT-PCR; local laboratory
SARS-CoV-2 serology; local laboratory (screening) a
a
SARS-CoV-2 serology test at screening will be analysed in a local laboratory. Subsequent SARS-CoV-2 
serology tests after screening will be analysed in a central laboratory (see Section 8.1.2).
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; qRT-PCR, quantitative reverse transcriptase 
polymerase chain reaction.
8.2.5
Monitoring of Administration of Study Intervention
Participants will be monitored during and after administration of study intervention. Vital 
signs will be measured before and after administration of study intervention according to time 
points specified in the SoA (Section 1.3).
As with any biologic product, hypersensitivity reactions (including anaphylaxis) and 
infusion-related reactions are possible. Therefore, appropriate drugs and medical equipment to 
treat these reactions must be immediately available, and study personnel must be trained to 
recognise and treat anaphylaxis.
Any AEs should be reported as described in Section 8.3.
8.3
Adverse Events and Serious Adverse Events
The principal investigator is responsible for ensuring that all staff involved in the study are 
familiar with the content of this section.
The definitions of an AE or SAE can be found in Appendix B.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorised representative).
The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE.
8.3.1
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information
Non-serious AEs and SAEs will be recorded from the time of signature of the ICF through the 
last participant contact.
If the investigator becomes aware of an SAE with a suspected causal relationship to the study 


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intervention that occurs after the end of the clinical study in a participant treated by him or 
her, the investigator shall, without undue delay, report the SAE to the sponsor.
8.3.2
Follow-up of Adverse Events and Serious Adverse Events
Any AEs that are unresolved at the participant’s last AE assessment in the study are followed 
up by the investigator for as long as medically indicated, but without further recording in the 
eCRF. AstraZeneca retains the right to request additional information for any participant with 
ongoing AE(s)/SAE(s) at the end of the study, if judged necessary.
Adverse Event Variables
The following variables will be collected for each AE:
#
AE (verbatim)
#
The date and time when the AE started and stopped
#
Maximum intensity
#
Whether the AE is serious or not
#
Investigator causality rating against the study intervention (yes or no)
#
Action taken with regard to study intervention
#
AE caused participant’s withdrawal from study (yes or no)
#
Outcome
In addition, the following variables will be collected for SAEs:
#
Date AE met criteria for SAE
#
Date investigator became aware of SAE
#
AE is serious due to
#
Date of hospitalisation
#
Date of discharge
#
Probable cause of death
#
Date of death
#
Autopsy performed
#
Causality assessment in relation to study procedure(s)
#
Causality assessment to other medication
8.3.3 Causality Collection
The investigator should assess causal relationship between study intervention and each AE, 


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and answer ‘yes’ or ‘no’ to the question ‘Do you consider that there is a reasonable possibility 
that the event may have been caused by the study intervention?’
For SAEs, causal relationship should also be assessed for other medication and study 
procedures. Note that for SAEs that could be associated with any study procedure the causal 
relationship is implied as ‘yes’.
A guide to the interpretation of the causality question is found in Appendix B.
8.3.4 Adverse Events of Special Interest
Adverse events of special interest are events of scientific and medical interest, specific to the 
further understanding of the study intervention safety profile, and require close monitoring 
and rapid communication by the investigators to the sponsor. An AESI can be serious or non-
serious. All AESIs will be recorded in the eCRF. Serious AESIs will be recorded and reported 
as per Section 8.3.8. See also the AZD7442 Investigator’s Brochure for additional information 
on AESIs.
The AESIs for AZD7442 include:
#
Anaphylaxis and other serious hypersensitivity reactions, including immune complex 
disease
#
Infusion-related reactions
8.3.5 Adverse Events Based on Signs and Symptoms
All AEs spontaneously reported by the participant or care provider or reported in response to 
the open question from the study site staff: ‘Have you had any health problems since the 
previous visit/you were last asked?’, or revealed by observation will be collected and recorded 
in the eCRF. When collecting AEs, the recording of diagnoses is preferred (when possible) to 
recording a list of signs and symptoms. However, if a diagnosis is known and there are other 
signs or symptoms that are not generally part of the diagnosis, the diagnosis and each sign or 
symptom will be recorded separately.
8.3.6 Adverse Events Based on Examinations and Tests
The results from the CSP-mandated laboratory tests and vital signs will be summarised in the 
CSR.
Abnormal results of examination and tests at screening (eg, haematology, clinical chemistry, 
urinalysis, ECG, physical examination, vital signs, etc.) are regarded as existing conditions 
before ICF and will not be recorded as AE. Relevant clinically significant abnormality of 
examination and tests during screening can be recorded as medical history according to 
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Deterioration as compared to baseline in protocol-mandated laboratory values and vital signs 
should therefore only be reported as AEs if they fulfil any of the SAE criteria, are the reason 
for discontinuation of treatment with the investigational product or are considered to be 
clinically relevant as judged by the investigator (which may include but is not limited to 
consideration as to whether treatment or non-planned visits were required or other action was 
taken with the study intervention, eg, dose adjustment or drug interruption).
If deterioration in a laboratory value/vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated laboratory result/vital sign 
will be considered as additional information. Wherever possible, the reporting investigator 
uses the clinical, rather than the laboratory term (eg, anaemia versus low haemoglobin value). 
In the absence of clinical signs or symptoms, clinically relevant deteriorations in non-
mandated parameters should be reported as AE(s).
Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the screening assessment may be reported as an AE.
8.3.7 Hy’s Law
Cases where a participant shows elevations in liver biochemistry may require further 
evaluation and occurrences of AST or ALT ≥3 × ULN together with TBL ≥2 × ULN may 
need to be reported as SAEs. Please refer to Appendix D for further instruction on cases of 
increases in liver biochemistry and evaluation of Hy’s Law.
8.3.8
Reporting of Serious Adverse Events
All SAEs must be reported, whether or not considered causally related to the investigational 
product, or to the study procedure(s). All SAEs will be recorded in the eCRF.
If any SAE occurs in the course of the study, investigators or other site personnel will inform 
the appropriate AstraZeneca representatives within 1 day, ie, immediately but no later than 
24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative will work with the investigator to ensure that all 
the necessary information is provided to the AstraZeneca Patient Safety data entry site within 
1 calendar day of initial receipt for fatal and life-threatening events and within 5 calendar
days of initial receipt for all other SAEs.
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up will be undertaken immediately. Investigators or other site personnel will inform 
AstraZeneca representatives of any follow-up information on a previously reported SAE 
within 1 calendar day, ie, immediately but no later than 24 hours of when he or she becomes 
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Once the investigators or other site personnel indicate an AE is serious in the EDC system, an 
automated email alert is sent to the designated AstraZeneca representative.
If the EDC system is not available, then the investigator or other study site staff reports an 
SAE to the appropriate AstraZeneca representative by telephone.
The AstraZeneca representative will advise the investigator/study site staff how to proceed.
The reference document for definition of expectedness/listedness is the Investigator’s 
Brochure for the AstraZeneca drug.
8.3.9
Pregnancy
All pregnancies and outcomes of pregnancy should be reported to AstraZeneca except if the 
pregnancy is discovered before the study participant has received any study intervention.
8.3.9.1
Maternal Exposure
The study intervention should not be given to pregnant women.
Pregnancy itself is not regarded as an AE unless there is a suspicion that the study intervention 
may have interfered with the effectiveness of a contraceptive medication. Congenital 
anomalies/birth defects and spontaneous miscarriages should be reported and handled as 
SAEs. Elective abortions without complications should not be handled as AEs. The outcome 
of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal 
birth or congenital anomaly) should be followed up and documented even if the participant 
was discontinued from the study.
If any pregnancy occurs in the course of the study, then the investigator or other site personnel 
informs the appropriate AstraZeneca representatives within 1 day, ie, immediately but no 
later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site within 1 or 
5 calendar days for SAEs (see Section 8.3.8) and within 30 days for all other pregnancies.
The same timelines apply when outcome information is available.
The PREGREP module in the eCRF is used to report the pregnancy and the paper-based 
PREGOUT module is used to report the outcome of the pregnancy.
8.3.9.2
Paternal Exposure 
Male participants should refrain from fathering a child during the study and for 365 days 
following the administration of study intervention.


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In case of pregnancy of the partner of a male participant, the partner’s pregnancy should be 
reported on the pregnancy form (consent from the partner must be obtained before the 
pregnancy form is completed) following the same timeframe and routing as described for any 
participant’s pregnancy. Pregnancy of the participant’s partner is not considered to be an AE. 
The pregnancy will also be followed up, and the outcome of the pregnancy (spontaneous 
miscarriage, elective termination, ectopic pregnancy, normal birth or congenital anomaly) 
should, if possible, be obtained and documented.
8.3.10
Medication Error
If a medication error occurs in the course of the study, then the investigator or other site 
personnel informs the appropriate AstraZeneca representatives within 1 day, ie, immediately 
but no later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is completed within 1 (initial fatal/life-threatening or follow-up fatal/life-
threatening) or 5 (other serious initial and follow-up) calendar days if there is an SAE 
associated with the medication error (see Section 8.3.8) and within 30 days for all other 
medication errors.
The definition of a medication error can be found in Appendix B 4.
8.4
Overdose
For this study, any dose of study intervention greater than the assigned dosage will be 
considered an overdose.
#
An overdose with associated AEs is recorded as the AE diagnosis/symptoms on the 
relevant AE modules in the eCRF and on the Overdose eCRF module.
#
An overdose without associated symptoms is only reported on the Overdose eCRF 
module.
If an overdose on an AstraZeneca study intervention occurs in the course of the study, the 
investigator or other site personnel inform appropriate AstraZeneca representatives 
immediately, but no later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site within 1 or 
5 calendar days for overdoses associated with an SAE (see Section 8.3.8) and within 30 days
for all other overdoses.


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8.5
Human Biological Samples
Instructions for the collection and handling of biological samples will be provided in the study 
specific laboratory manual. Samples should be stored in a secure storage space with adequate 
measures to protect confidentiality. For further details on handling of human biological 
samples, see Appendix C.
Samples will be stored to properly address potential questions from regulatory agencies or for 
a maximum of 2 years following the date of issue of the final CSR (whichever is earlier) in 
line with consent and local requirements, after which they will be destroyed.
#
The PK samples will be disposed of after the Bioanalytical Report finalisation or 
6 months after issuance of the draft Bioanalytical Report (whichever is earlier).
%
The PK samples may be disposed of or anonymised by pooling. Additional analyses 
may be conducted on the anonymised, pooled PK samples to further evaluate and 
validate the analytical method. Any results from such analyses may be reported 
separately from the CSR.
#
ADA sample aliquots and PD (as neutralising activity in serum) samples will be retained 
at AstraZeneca or its designee to properly address potential questions from regulatory 
agencies or for a maximum of 2 years following the date of issue of the final CSR 
(whichever is earlier) in line with consent and local requirements, after which they will be 
destroyed. Additional use includes further characterisation of any ADAs, confirmation 
and/or requalification of the assay, as well as additional assay development work based 
on regulatory requirement or feedback. The results from additional analysis may be 
reported separately from the CSR.
8.5.1
Pharmacokinetics
#
Blood samples will be collected for measurement of serum concentrations of AZD7442 
(AZD8895 and AZD1061) at time points specified in the SoA (Section 1.3).
#
Serum samples will be used to analyse the PK of AZD7442.
#
Samples will be collected, labelled, stored, and shipped as detailed in the Laboratory 
Manual.
8.5.1.1
Determination of Drug Concentration
Samples for determination of drug concentration in serum will be assayed by bioanalytical test 
sites operated by or on behalf of AstraZeneca, using an appropriately validated bioanalytical 
method. Full details of the analytical method used will be described in a separate bioanalytical 
report.
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investigative sites or blinded personnel until the study has been unblinded.
Incurred sample reproducibility analysis, if any, will be performed alongside the bioanalysis 
of the test samples. The results from the evaluation, if performed, will be reported in a 
separate Bioanalytical Report.
8.5.1.2
Pharmacokinetic Parameters
Where possible, the PK parameters will be estimated for AZD7442 (each mAb: AZD8895 and 
AZD1061) based on serum concentrations.
Cmax
Maximum concentration
AUC(0-180days)
Area under the concentration-curve from time zero to 180 days
AUClast
Area under the concentration-curve from time zero to the time of last quantifiable 
concentration
AUCinf
Area under the concentration-time curve from time zero extrapolated to infinity 
t½λz
Terminal elimination half-life, estimated as (ln2)/∀z
tlast
Time of last quantifiable concentration
Vss
Volume of distribution at steady state
Vz
Volume of distribution based on terminal phase
CL
Clearance
The following parameters will be calculated for PK diagnostic purposes and will also be 
summarised.
λz lower
Lower (earlier) t used for λz determination
λz upper
Upper (later) t used for λz determination
λzN
Number of data points included in the log-linear regression analysis
λz span ratio
Time period over which λz was determined as ratio of t½λz
Rsq_adj
Statistical measure of fit for the regression used for λz determination adjusted for the 
number of used data points (n obs)
λz
Terminal elimination rate constant
AUCextr
Extrapolated area under the curve from tlast to infinity, expressed as percentage of 
AUCinf
Additional serum PK parameters may be determined where appropriate.
The bioanalytical analysis of the serum concentration for AZD7442 mAbs (AZD8895 and 
AZD1061) will be performed at bioanalytical test sites operated by or on behalf of 
AstraZeneca, using an appropriately validated bioanalytical method.
The PK data analysis will, where data allow, be carried out using actual time after dose 


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determined from the PK sampling and dosing times recorded in the database. If actual times 
are missing, nominal times may be used.
8.5.2
Pharmacodynamics
#
Blood samples for the determination of PD as 
 
 will be collected at time points specified in the SoA (Section 1.3) 
and will be analysed provided the analysis method is established and appropriate approval 
has been obtained.
#
Samples will be collected, labelled, stored, and shipped as detailed in the Laboratory 
Manual.
For storage, re-use, and destruction of PD samples, see Section 8.5 and Appendix C.
8.5.3
Immunogenicity Assessments
Blood samples for determination of ADA in serum will be collected as specified in the SoA 
(Section 1.3) and will be assayed by bioanalytical test sites operated by or on behalf of 
AstraZeneca, using an appropriately validated bioanalytical method. Full details of the 
methods used will be described in a separate report.
ADA samples may also be further tested for characterisation of the ADA response.
Samples will be collected, labelled, stored, and shipped as detailed in the Laboratory Manual.
8.6
Human Biological Sample Biomarkers
Not applicable.
8.7
Optional Genomics Initiative Sample
Not applicable.
8.8
Medical Resource Utilisation and Health Economics
Not applicable.
9
STATISTICAL CONSIDERATIONS
9.1
Statistical Hypotheses
No statistical hypotheses will be evaluated based on formal statistical tests. Descriptive 
statistics will be presented for relevant data and parameters.
9.2
Sample Size Determination
Approximately 272 participants will be randomised 3:1 to study intervention with 600 mg 
CCI


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AZD7442 (n = 204) or placebo (n = 68) administered IV. If the true AE rate is 1% at the 
primary time point (ie, Month 6), 162 participants in the AZD7442 group will provide a 
probability of at least 80% to observe at least one AE case. A dropout rate of 20% is assumed.
The 1% assumption is driven by the international convention where 1% is used as the lower 
limit of common AEs (between infrequent and frequent AEs) (CIOMS 1999). The 
randomisation ratio of 3:1 limits the number of participants in the placebo group so that 
adequate information can be obtained to objectively assess the safety of AZD7442 in the 
Chinese population.
Note: “Enrolled” means a participant’s, or their representative’s agreement to participate in a 
clinical study following completion of the informed consent process. Potential participants 
who are screened for the purpose of determining eligibility for the study, but are not randomly 
assigned in the study, are considered “screen failures”, unless otherwise specified by the 
protocol.


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9.3
Populations for Analyses
The populations for analysis are defined in Table 13.
Table 13
Populations for Analysis
Population/analysis set
Description
All participants
All participants who signed the ICF.
Randomised
All participants who were randomised in the study.
Full
All randomised participants who received any amount of AZD7442 or 
placebo, irrespective of their protocol adherence and continued participation 
in the study.
Participants will be analysed according to their randomised treatment, 
irrespective of whether or not they have prematurely discontinued, 
according to the intent-to-treat principle. Participants who withdraw consent 
to participate in the study will be included up to the date of their study 
termination.
Safety
All participants who received any amount of AZD7442 or placebo.
Erroneously treated participants (eg, those randomised to intervention A but 
actually given intervention B) will be analysed according to the intervention 
they actually receive.
PK
All participants in the safety analysis set who received AZD7442 and had at 
least one quantifiable serum PK observation post-dose, with no important 
protocol deviations thought to impact the analysis of the PK data.
ADA
All participants who received any amount of AZD7442 or placebo and had a 
non-missing baseline ADA result and at least one non-missing post-baseline 
ADA result.
PD
All participants in the safety analysis set who received AZD7442 or placebo 
and had at least one quantifiable titre observation post-dose, with no 
important protocol deviations thought to impact the analysis of the PD data.
ADA, antidrug antibody; ICF, informed consent form; PD, pharmacodynamics; PK, pharmacokinetic; 
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Participant disposition will be reported using the all participants analysis set. 
Pharmacokinetics will be assessed using the PK analysis set. Pharmacodynamics will be 
assessed using the PD analysis set. 
 
 Immunogenicity will be assessed using the ADA analysis set. All remaining 
evaluations including safety analysis will use the safety analysis set, unless otherwise stated.
9.4
Statistical Analyses
The primary DBL will occur after all treated participants have completed follow-up through 
Day 181 to conduct the primary analysis. All available data at the time of DBL will be 
included in the primary analysis. No early stopping decision will be made for futility or 
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superiority at the primary analysis.
All participants in the study will be assessed for safety and tolerability, PK, and PD for 
approximately 15 months following the dose of study intervention (through Day 451). A final 
DBL will occur when all participants have completed the study.
The SAP will be finalised within 90 days of the First Subject In or the first DSMB meeting, 
whichever comes first, and prior to the primary DBL and it will include a more technical and 
detailed description of the statistical analyses described in this section. This section is a 
summary of the planned statistical analyses of the most important endpoints.
9.4.1
General Considerations
The study will initially be double-blind until the primary analysis (ie, blind for participants, 
investigators/site staff, and sponsor/designated clinical research organisation). To maintain the 
integrity of the study to allow rigorous evaluation of study objectives through the end of the 
study, investigators and participants will remain blinded to the intervention assignment until 
the end of the study. The sponsor may be unblinded after the primary DBL as needed to 
perform the analysis and planning.
Unless otherwise stated, the as-treated principle will be applied to study evaluations, which is 
participants who received study intervention other than the one assigned by randomisation 
will be analysed as belonging to the actual intervention received.
Categorical variables will be summarised using frequency and percentages, where the 
denominator for calculation is the underlying analysis set population, unless otherwise stated.
Continuous variables will be summarised with descriptive statistics of number of available 
observations, mean, standard deviation, median, minimum, maximum, and quartiles as 
appropriate.
9.4.2
Efficacy
The efficacy objective and endpoints are considered exploratory, and no hypothesis testing 
will be evaluated. Efficacy data will be presented based on the full analysis set. The results 
may be reported separately from the CSR. Details will be described in the SAP.
9.4.3
Safety
Safety data will be summarised by intervention group on the safety analysis set, unless 
otherwise specified. In general, the baseline value for summaries is the last non-missing value 
prior to administration of the first dose of study intervention. Details will be described in the 
SAP.


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9.4.3.1
Primary Endpoint(s)
The safety of AZD7442 will primarily be assessed by AEs.
Adverse events will be presented for each intervention group by system organ class and/or 
preferred term covering the number and percentage of participants reporting at least one event 
and number of events where appropriate.
An overview of AEs will be presented for each intervention group showing the number and 
percentage of participants with any AE, any SAE, any SAE with outcome of death, and other 
AE categories as appropriate.
Summaries may be provided for AEs, SAEs, SAEs with outcome of death, AESIs, and other 
AE categories as appropriate. Additional summaries will be provided taking into consideration 
the relationship as assessed by the investigator as well as maximum intensity. The AE severity 
will be graded according to Appendix B and coded using the most recent version of the 
Medical Dictionary for Regulatory Activities.
An AE listing for the safety analysis set will cover details for each individual AE. Full details 
of AE analyses will be provided in the SAP.
9.4.3.2
Other Safety Endpoint(s)
Other safety endpoints include:
#
Laboratory parameters (haematology, clinical chemistry, coagulation, and urinalysis)
#
Vital signs (blood pressure, pulse rate, body temperature, and respiratory rate)
#
12-lead safety ECG
#
Physical examination
Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the baseline assessment will be reported as an AE.
All parameters from laboratory, ECG, and vital signs will be summarised by intervention 
group with descriptive statistics based on data type (continuous, categorical, etc).
For each scheduled post-baseline visit, descriptive statistics parameters will be presented for 
observed values and change from baseline as appropriate. Shift tables presenting number and 
percentage of participants in the respective category may be provided.
Full details of safety endpoint analysis will be provided in the SAP.
9.4.4
Pharmacokinetic Analyses
The AZD7442 mAbs (AZD8895 and AZD1061) concentrations measured from serum at each 


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time point will be summarised based on the PK analysis set, using the appropriate descriptive 
statistics. Individual and mean of serum concentrations over time will be plotted, on both 
linear and semi-logarithmic scale.
The PK parameters will be derived using noncompartmental methods and will be summarised 
based on the PK analysis set, using the appropriate descriptive statistics.
Potential correlation between PK exposure and safety response may be explored. Population 
PK analysis may be performed and reported in a separate report.
9.4.5
Pharmacodynamic Analyses
All available data of serum neutralising responses against SARS-CoV-2 will be listed and 
presented in tabular and graphical form as appropriate. The serum neutralising responses 
against SARS-CoV-2 will be summarised by intervention group using geometric mean titre 
and geometric mean fold rise from baseline, based on the PD analysis set.
Results of the evaluation of the functional inhibition of SARS-CoV-2 by AZD7442 
concentrations in serum may be reported separately from the CSR.
9.4.6
Immunogenicity Analyses
A summary of the number and percentage of participants who developed detectable ADA to 
AZD7442 (ADA results to AZD8895 and AZD1061 will be reported separately) by ADA 
categories will be presented by intervention group based on the ADA evaluable analysis set. 
The ADA titre will be presented for samples confirmed positive for the presence of ADA to 
AZD7442. Samples confirmed positive for ADA may be further tested, including possible 
assessments of neutralising antibodies.
The potential effects of immunogenicity on PK or safety of AZD7442 may be evaluated, if 
appropriate.
9.5
Interim Analyses
As no multiplicity control is applied, ad-hoc interim analyses may be performed, if warranted, 
for additional evaluation of a potential signal in the safety profile.
9.6
Data Safety Monitoring Board
An independent DSMB will provide oversight, to ensure safe and ethical conduct of the study. 
The DSMB will have the responsibility of evaluating cumulative safety and other clinical trial 
data at regular intervals and making appropriate recommendations based on the available data. 
During the study, the benefit/risk assessment will be continuously monitored by the DSMB to 
ensure that the balance remains favourable. If required, the DSMB will recommend 
temporarily stopping or termination of the study. There is no formal efficacy review by the 


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DSMB with the potential for early stopping due to efficacy planned for this study.
For details on the DSMB, refer to Appendix A 5.
10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS


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Appendix A
Regulatory, Ethical, and Study Oversight Considerations
A 1
Regulatory and Ethical Considerations
#
This study will be conducted in accordance with the protocol and with the following:
%
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organisations of Medical 
Sciences (CIOMS) International Ethical Guidelines.
%
Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines.
%
Applicable laws and regulations.
#
The protocol, protocol amendments, informed consent form (ICF), Investigator’s 
Brochure, and other relevant documents (eg, advertisements) must be submitted to an 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) by the 
investigator and reviewed and approved by the IRB/IEC before the study is initiated.
#
Any amendments to the protocol will require IRB/IEC and applicable Regulatory 
Authority approval before implementation of changes made to the study design, except 
for changes necessary to eliminate an immediate hazard to study participants.
#
AstraZeneca will be responsible for obtaining the required authorisations to conduct the 
study from the concerned Regulatory Authority. This responsibility may be delegated to a 
contract research organisation (CRO) but the accountability remains with AstraZeneca.
#
The investigator will be responsible for providing oversight of the conduct of the study at 
the site and adherence to requirements of 21 Code of Federal Regulations (CFR), ICH 
guidelines, the IRB/IEC, European Regulation 536/2014 for clinical studies (if 
applicable), European Medical Device Regulation 2017/745 for clinical device research 
(if applicable), and all other applicable local regulations.
Regulatory Reporting Requirements for Serious Adverse Events
#
Prompt notification by the investigator to the sponsor of a serious adverse event (SAE) is 
essential so that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study intervention under clinical investigation are met.
#
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRBs/IECs, and investigators.
#
For all studies except those utilising medical devices, investigator safety reports must be 
prepared for suspected unexpected serious adverse reactions (SUSAR) according to local 
regulatory requirements and sponsor policy and forwarded to investigators as necessary.


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%
European Medical Device Regulation 2017/745 for clinical device research (if 
applicable), and all other applicable local regulations.
#
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate according to local requirements.
A 2
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for one year after completion of the study.
A 3
Informed Consent Process
#
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorised representative and answer all questions regarding 
the study.
#
Participants must be informed that their participation is voluntary and they are free to 
refuse to participate and may withdraw their consent at any time and for any reason 
during the study. Participants or their legally authorised representative will be required to 
sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/IEC or study centre.
#
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorised person obtaining the informed consent must also sign the ICF.
#
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study.
#
A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorised representative.
Participants who are rescreened are required to sign a new ICF.
A 4
Data Protection
#
Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will contain the identifier only; participant 


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names or any information which would make the participant identifiable will not be 
transferred.
#
The participant must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection law. The level of disclosure and use 
of their data must also be explained to the participant in the informed consent.
#
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorised personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities.
A 5
Committees Structure
An independent Data Safety Monitoring Board (DSMB) will monitor and protect the safety of 
the participants throughout the study. The DSMB members will be selected for their expertise. 
The voting members of the DSMB will be comprised of external individuals, including the 
DSMB chair. Summaries of unblinded data will be reviewed by the DSMB during the study 
on a regular basis. To minimise the potential introduction of bias, DSMB members will not 
have direct contact with the study site personnel or participants. The data for review will be 
outlined in the DSMB Charter and will be agreed in advance by the DSMB members.
The DSMB will review safety data on a regular basis as set out in the DSMB Charter, 
including, but not limited to, reviewing the safety data from all participants during the study.
The DSMB can recommend modifications of the protocol to enhance participant safety and to 
recommend early termination of the study if there is strong evidence that AZD7442 or 
continuation of the study poses a safety concern to participants.
As no efficacy endpoints will be evaluated as study objectives, the primary/interim analysis 
will be conducted by AstraZeneca Clinical Study Team or delegates and the primary/interim 
results will be reviewed by the DSMB.
A 6
Dissemination of Clinical Study Data
A description of this clinical study will be available on 
http://astrazenecagrouptrials.pharmacm.com and http://www.clinicaltrials.gov as will the 
summary of the study results when they are available. The clinical study and/or summary of 
study results may also be available on other websites according to the regulations of the 
countries in which the study is conducted.
A 7
Data Quality Assurance
#
All participant data relating to the study will be recorded on an electronic case report form 
(eCRF) unless transmitted to the sponsor or designee electronically (eg, laboratory data). 


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The investigator is responsible for verifying that data entries are accurate and correct by 
electronically signing the eCRF.
#
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.
#
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.
#
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site monitoring) 
are provided in the Monitoring Plan and Protocol Deviations Plan.
#
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.
#
The sponsor assumes accountability for actions delegated to other individuals (eg, CROs).
#
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorised site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements.
#
Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator for 15 years after study completion unless local 
regulations or institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the sponsor. No 
records may be transferred to another location or party without written notification to the 
sponsor.
A 8
Source Documents
#
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site.
#
Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available.
#
Definition of what constitutes source data can be found in the Source Data Agreement 
and Clinical Study Agreement.


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A 9
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the first site open and will be the study start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:
#
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines.
#
Inadequate recruitment of participants by the investigator.
#
Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Participants from terminated sites will have the opportunity to be transferred to another site to 
continue the study.
A 10
Publication Policy
#
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor 
before submission. This allows the sponsor to protect proprietary information and to 
provide comments.
#
The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicentre studies only in their entirety and not as individual site data. In 
this case, a coordinating investigator will be designated by mutual agreement.


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#
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.


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Appendix B
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
B 1
Definition of Adverse Events
An adverse event (AE) is the development of any untoward medical occurrence in a patient or 
clinical study participant administered a medicinal product and which does not necessarily 
have a causal relationship with this treatment. An AE can therefore be any unfavourable and 
unintended sign (eg, an abnormal laboratory finding), symptom (for example nausea, chest 
pain), or disease temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product.
The term AE is used to include both serious and non-serious AEs and can include a 
deterioration of a pre-existing medical occurrence. An AE may occur at any time, including 
run-in or washout periods, even if no study intervention has been administered.
B 2
Definition of Serious Adverse Events
A serious adverse event (SAE) is an AE occurring during any study phase (ie, run-in, 
treatment, washout, follow-up), that fulfils one or more of the following criteria:
#
Results in death
#
Is immediately life-threatening
#
Requires in-patient hospitalisation or prolongation of existing hospitalisation
#
Results in persistent or significant disability or incapacity
#
Is a congenital anomaly or birth defect
#
Is an important medical event that may jeopardise the participant or may require medical 
treatment to prevent one of the outcomes listed above
Adverse events for malignant tumours reported during a study should generally be assessed 
as serious AEs. If no other seriousness criteria apply, the ‘Important Medical Event’ criterion 
should be used. In certain situations, however, medical judgment on an individual event basis 
should be applied to clarify that the malignant tumour event should be assessed and reported 
as a non-serious AE. For example, if the tumour is included as medical history and 
progression occurs during the study, but the progression does not change treatment and/or 
prognosis of the malignant tumour, the AE may not fulfil the attributes for being assessed as 
serious, although reporting of the progression of the malignant tumour as an AE is valid and 
should occur. Also, some types of malignant tumours, which do not spread remotely after a 
routine treatment that does not require hospitalisation, may be assessed as non-serious; 
examples in adults include Stage 1 basal cell carcinoma and Stage 1A1 cervical cancer 
removed via cone biopsy.


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Life-threatening
‘Life-threatening’ means that the participant was at immediate risk of death from the AE as it 
occurred or it is suspected that use or continued use of the product would result in the 
participant’s death. ‘Life-threatening’ does not mean that had an AE occurred in a more severe 
form it might have caused death (eg, hepatitis that resolved without hepatic failure).
Hospitalisation
Outpatient treatment in an emergency room is not in itself an SAE, although the reasons for it 
may be (eg, bronchospasm, laryngeal oedema). Hospital admissions and/or surgical operations 
planned before or during a study are not considered AEs if the illness or disease existed before 
the participant was enrolled in the study, provided that it did not deteriorate in an unexpected 
way during the study.
Important Medical Event or Medical Treatment
Medical and scientific judgment should be exercised in deciding whether a case is serious in 
situations where important medical events may not be immediately life-threatening or result in 
death, hospitalisation, disability or incapacity but may jeopardise the participant or may 
require medical treatment to prevent one or more outcomes listed in the definition of serious. 
These should usually be considered as serious.
Simply stopping the suspect drug does not mean that it is an important medical event; medical 
judgment must be used.
#
Angioedema not severe enough to require intubation but requiring intravenous 
hydrocortisone treatment
#
Hepatotoxicity caused by paracetamol (acetaminophen) overdose requiring treatment with 
N-acetylcysteine
#
Intensive treatment in an emergency room or at home for allergic bronchospasm
#
Blood dyscrasias (eg, neutropenia or anaemia requiring blood transfusion, etc.) or 
convulsions that do not result in hospitalisation
#
Development of drug dependency or drug abuse
Intensity Rating Scale:
#
Mild (awareness of sign or symptom, but easily tolerated)
#
Moderate (discomfort sufficient to cause interference with normal activities)
#
Severe (incapacitating, with inability to perform normal activities)
It is important to distinguish between serious and severe AEs. Severity is a measure of 


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intensity whereas seriousness is defined by the criteria in Appendix B 2. An AE of severe 
intensity need not necessarily be considered serious. For example, nausea that persists for 
several hours may be considered severe nausea, but not an SAE unless it meets the criteria 
shown in Appendix B 2. On the other hand, a stroke that results in only a limited degree of 
disability may be considered a mild stroke but would be an SAE when it satisfies the criteria 
shown in Appendix B 2.
B 3
A Guide to Interpreting the Causality Question
When making an assessment of causality consider the following factors when deciding if there 
is a ‘reasonable possibility’ that an AE may have been caused by the drug.
#
Time Course. Exposure to suspect drug. Has the participant actually received the suspect 
drug? Did the AE occur in a reasonable temporal relationship to the administration of the 
suspect drug?
#
Consistency with known drug profile. Was the AE consistent with the previous 
knowledge of the suspect drug (pharmacology and toxicology) or drugs of the same 
pharmacological class? Or could the AE be anticipated from its pharmacological 
properties?
#
De-challenge experience. Did the AE resolve or improve on stopping or reducing the dose 
of the suspect drug?
#
No alternative cause. The AE cannot be reasonably explained by another aetiology such 
as the underlying disease, other drugs, other host or environmental factors.
#
Re-challenge experience. Did the AE reoccur if the suspected drug was reintroduced after 
having been stopped? AstraZeneca would not normally recommend or support a 
re-challenge.
#
Laboratory tests. A specific laboratory investigation (if performed) has confirmed the 
relationship.
In difficult cases, other factors could be considered such as:
#
Is this a recognised feature of overdose of the drug?
#
Is there a known mechanism?
Causality of ‘related’ is made if following a review of the relevant data, there is evidence for a 
‘reasonable possibility’ of a causal relationship for the individual case. The expression 
‘reasonable possibility’ of a causal relationship is meant to convey, in general, that there are 
facts (evidence) or arguments to suggest a causal relationship.
The causality assessment is performed based on the available data including enough 


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information to make an informed judgment. With no available facts or arguments to suggest a 
causal relationship, the event(s) will be assessed as ‘not related’.
Causal relationship in cases where the disease under study has deteriorated due to lack of 
effect should be classified as no reasonable possibility.
B 4
Medication Error
For the purposes of this clinical study a medication error is an unintended failure or mistake in 
the treatment process for an AstraZeneca study intervention that either causes harm to the 
participant or has the potential to cause harm to the participant.
A medication error is not lack of efficacy of the drug, but rather a human or process related 
failure while the drug is in control of the study site staff or participant.
Medication error includes situations where an error.
#
Occurred
#
Was identified and intercepted before the participant received the drug
#
Did not occur, but circumstances were recognised that could have led to an error
Examples of events to be reported in clinical studies as medication errors:
#
Drug name confusion
#
Dispensing error, eg, medication prepared incorrectly, even if it was not actually given to 
the participant
#
Drug not administered as indicated, eg, wrong route or wrong site of administration
#
Drug not taken as indicated, eg, tablet dissolved in water when it should be taken as a 
solid tablet
#
Drug not stored as instructed, eg, kept in the refrigerator when it should be at room 
temperature 
#
Wrong participant received the medication (excluding Interactive Response Technology 
[IRT]/Randomisation and Trial Supply Management [RTSM] errors)
#
Wrong drug administered to participant (excluding IRT/RTSM errors)
Examples of events that do not require reporting as medication errors in clinical studies:
#
Errors related to or resulting from IRT/RTSM - including those which lead to one of the 
above listed events that would otherwise have been a medication error
#
Participant accidentally missed drug dose(s), eg, forgot to take medication


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#
Accidental overdose (will be captured as an overdose)
#
Participant failed to return unused medication or empty packaging
#
Errors related to background and rescue medication, or standard of care medication in 
open label studies, even if an AstraZeneca product 
Medication errors are not regarded as AEs but AEs may occur as a consequence of the 
medication error.


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Appendix C
Handling of Human Biological Samples
C 1
Chain of Custody
A full chain of custody is maintained for all samples throughout their lifecycle.
The investigator keeps full traceability of collected biological samples from the participants 
while in storage at the centre until shipment or disposal (where appropriate) and records 
relevant processing information related to the samples whilst at site.
The sample receiver keeps full traceability of the samples while in storage and during use until 
used or disposed of or until further shipment and keeps record of receipt of arrival and onward 
shipment or disposal.
AstraZeneca or delegated representatives will keep oversight of the entire lifecycle through 
internal procedures, monitoring of study sites, auditing or process checks, and contractual 
requirements of external laboratory providers.
Samples retained for further use will be stored in the AstraZeneca-assigned biobanks or other 
sample archive facilities and will be tracked by the appropriate AstraZeneca Team during for 
the remainder of the sample lifecycle.
C 2
Withdrawal of Informed Consent for Donated Biological Samples 
AstraZeneca ensures that biological samples are destroyed at the end of a specified period as 
described in the informed consent.
If a participant withdraws consent to the use of donated biological samples, the samples will 
be disposed of/destroyed/repatriated, and the action documented. If samples are already 
analysed, AstraZeneca is not obliged to destroy the results of this research.
Following withdrawal of consent for biological samples, further study participation should be 
considered in relation to the withdrawal processes outlined in the informed consent.
The investigator:
#
Ensures participant’s withdrawal of informed consent to the use of donated samples is 
highlighted immediately to AstraZeneca or delegate.
#
Ensures that relevant human biological samples from that participant, if stored at the 
study site, are immediately identified, disposed of as appropriate, and the action 
documented.
#
Ensures that the participant and AstraZeneca are informed about the sample disposal.
AstraZeneca ensures the organisation(s) holding the samples is/are informed about the 


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withdrawn consent immediately and that samples are disposed of or repatriated as appropriate, 
and the action is documented and study site is notified.
C 3
International Airline Transportation Association 6.2 Guidance 
Document
LABELLING AND SHIPMENT OF BIOHAZARD SAMPLES
International Airline Transportation Association (IATA) 
(https://www.iata.org/whatwedo/cargo/dgr/Pages/download.aspx) classifies infectious 
substances into 3 categories: Category A, Category B or Exempt
Category A Infectious Substances are infectious substances in a form that, when exposure to 
them occurs, are capable of causing permanent disability or life-threatening or fatal disease in 
otherwise healthy humans or animals. 
Category A Pathogens are, eg, Ebola, Lassa fever virus. Infectious substances meeting these 
criteria which cause disease in humans or both in humans and animals must be assigned to 
UN 2814. Infectious substances which cause disease only in animals must be assigned to 
UN 2900.
Category B Infectious Substances are infectious substances that do not meet the criteria for 
inclusion in Category A. Category B pathogens are, eg, Hepatitis A, C, D, and E viruses. They 
are assigned the following UN number and proper shipping name:
#
UN 3373 – Biological Substance, Category B
#
Are to be packed in accordance with UN 3373 and IATA 650
Exempt - Substances which do not contain infectious substances or substances which are 
unlikely to cause disease in humans or animals are not subject to these Regulations unless they 
meet the criteria for inclusion in another class.
#
Clinical study samples will fall into Category B or exempt under IATA regulations.
#
Clinical study samples will routinely be packed and transported at ambient temperature in 
IATA 650 compliant packaging 
(https://www.iata.org/whatwedo/cargo/dgr/Documents/DGR-60-EN-PI650.pdf).
#
Biological samples transported in dry ice require additional dangerous goods specification 
for the dry-ice content.


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Appendix D
Actions Required in Cases of Increases in Liver Biochemistry 
and Evaluation of Hy’s Law
D 1
Introduction
This Appendix describes the process to be followed in order to identify and appropriately 
report Potential Hy’s Law (PHL) cases and Hy’s Law (HL) cases. It is not intended to be a 
comprehensive guide to the management of elevated liver biochemistries.
During the course of the study the investigator will remain vigilant for increases in liver 
biochemistry. The investigator is responsible for determining whether a participant meets 
potential PHL criteria at any point during the study.
All sources of laboratory data are appropriate for the determination of PHL and HL events; 
this includes samples taken at scheduled study visits and other visits including central and all 
local laboratory evaluations even if collected outside of the study visits; for example, PHL 
criteria could be met by an elevated alanine aminotransferase (ALT) from a central laboratory 
and/or elevated total bilirubin (TBL) from a local laboratory.
The investigator will also review adverse event (AE) data (for example, for AEs that may 
indicate elevations in liver biochemistry) for possible PHL events.
The investigator participates, together with AstraZeneca clinical project representatives, in 
review and assessment of cases meeting PHL criteria to agree whether Hy’s Law (HL) criteria 
are met. Hy’s Law criteria are met if there is no alternative explanation for the elevations in 
liver biochemistry other than drug induced liver injury (DILI) caused by the investigational 
medicinal product (IMP).
The investigator is responsible for recording data pertaining to PHL/HL cases and for 
reporting serious adverse events (SAEs) and AEs according to the outcome of the review and 
assessment in line with standard safety reporting processes.
D 2
Definitions
Potential Hy’s Law
Aspartate aminotransferase (AST) or ALT ≥3 × upper limit of normal (ULN) together with
TBL ≥2× ULN at any point during the study following the start of study medication
irrespective of an increase in alkaline phosphatase (ALP).
Hy’s Law
AST or ALT ≥3× ULN together with TBL ≥2× ULN, where no other reason, other than the 
IMP, can be found to explain the combination of increases, eg, elevated ALP indicating 
cholestasis, viral hepatitis, another drug.


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For PHL and HL the elevation in transaminases must precede or be coincident with (ie, on the 
same day) the elevation in TBL, but there is no specified timeframe within which the 
elevations in transaminases and TBL must occur.
D 3
Identification of Potential Hy’s Law Cases
In order to identify cases of PHL it is important to perform a comprehensive review of 
laboratory data for any participant who meets any of the following identification criteria in 
isolation or in combination:
#
ALT ≥3 × ULN
#
AST ≥3 × ULN
#
TBL ≥2 × ULN
When a participant meets any of the PHL identification criteria, in isolation or in combination, 
the central laboratory will immediately send an alert to the investigator (also sent to 
AstraZeneca representative). 
The investigator will also remain vigilant for any local laboratory reports where the PHL 
identification criteria are met; where this is the case the investigator will:
#
Notify the AstraZeneca representative.
#
Request a repeat of the test (new blood draw) by the central laboratory without delay.
#
Complete the appropriate unscheduled laboratory electronic case report form (eCRF) 
module(s) with the original local laboratory test result.
When the identification criteria are met from central or local laboratory results, the 
investigator will without delay:
#
Determine whether the participant meets PHL criteria (see Section D 2 for definition) by 
reviewing laboratory reports from all previous visits (including both central and local 
laboratory results).
D 4
Follow-up
D 4.1
Potential Hy’s Law Criteria Not Met
If the participant does not meet PHL criteria the investigator will:
#
Inform the AstraZeneca representative that the participant has not met PHL criteria.


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#
Perform follow-up on subsequent laboratory results according to the guidance provided in 
the clinical study protocol (CSP).
D 4.2
Potential Hy’s Law Criteria Met
If the participant does meet PHL criteria the investigator will:
#
Notify the AstraZeneca representative who will then inform the central study team.
#
Within one day of PHL criteria being met, the investigator will report the case as an SAE 
of PHL; serious criteria ‘important medical event’ and causality assessment ‘yes/related’ 
according to CSP process for SAE reporting.
#
For participants that met PHL criteria prior to starting IMP, the investigator is not 
required to submit a PHL SAE unless there is a significant change# in the participant’s 
condition.
#
The study physician contacts the investigator, to provide guidance, discuss and agree an 
approach for the study participants’ follow-up (including any further laboratory testing) 
and the continuous review of data.
#
Subsequent to this contact the investigator will:
%
Monitor the participant until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as long as medically 
indicated. Complete follow-up SAE Form as required.
%
Investigate the aetiology of the event and perform diagnostic investigations as 
discussed with the study physician. This includes deciding which tests available in 
the Hy’s law lab kit should be used.
%
Complete the 3 liver eCRF modules as information becomes available.
#A ‘significant’ change in the participant’s condition refers to a clinically relevant change in 
any of the individual liver biochemistry parameters (ALT, AST, or TBL) in isolation or in 
combination, or a clinically relevant change in associated symptoms. The determination of 
whether there has been a significant change will be at the discretion of the investigator, this 
may be in consultation with the study physician if there is any uncertainty.
D 5
Review and Assessment of Potential Hy’s Law Cases
The instructions in this section should be followed for all cases where PHL criteria are met.
As soon as possible after the biochemistry abnormality was initially detected, the study 
physician contacts the investigator in order to review available data and agree on whether 
there is an alternative explanation for meeting PHL criteria other than DILI caused by the 
IMP, to ensure timely analysis and reporting to health authorities within 15 calendar days from 


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date PHL criteria was met. The AstraZeneca global clinical lead or equivalent and global 
safety physician will also be involved in this review together with other subject matter experts 
as appropriate. 
According to the outcome of the review and assessment, the investigator will follow the 
instructions below.
Where there is an agreed alternative explanation for the ALT or AST and TBL elevations, a 
determination of whether the alternative explanation is an AE will be made and subsequently 
whether the AE meets the criteria for an SAE:
#
If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate eCRF.
#
If the alternative explanation is an AE/SAE: update the previously submitted PHL SAE 
and AE eCRFs accordingly with the new information (reassessing event term; causality 
and seriousness criteria) following the AstraZeneca standard processes.
If it is agreed that there is no explanation that would explain the ALT or AST and TBL 
elevations other than the IMP:
#
Send updated SAE (report term ‘Hy’s Law’) according to AstraZeneca standard 
processes.
%
The ‘Medically Important’ serious criterion should be used if no other serious criteria 
apply
%
As there is no alternative explanation for the HL case, a causality assessment of 
‘related’ should be assigned.
If there is an unavoidable delay of over 15 calendar days in obtaining the information 
necessary to assess whether or not the case meets the criteria for HL, then it is assumed that 
there is no alternative explanation until such time as an informed decision can be made:
#
Provides any further update to the previously submitted SAE of Potential Hy’s Law, 
(report term now ‘Hy’s Law case’) ensuring causality assessment is related to IMP and 
seriousness criteria is medically important, according to CSP process for SAE reporting.
#
Continue follow-up and review according to agreed plan. Once the necessary 
supplementary information is obtained, repeat the review and assessment to determine 
whether HL criteria are still met. Update the previously submitted PHL SAE report 
following CSP process for SAE reporting, according to the outcome of the review and 
amending the reported term if an alternative explanation for the liver biochemistry 
elevations is determined.


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D 6
Laboratory Tests
The list below represents the standard, comprehensive list of follow-up tests which are 
recommended, but not mandatory, when using a central laboratory. The list may be modified 
based on clinical judgment. Any test results need to be recorded.
Hy’s Law Lab Kit for Central Laboratories
Additional standard chemistry and coagulation tests
GGT
LDH
Prothrombin time
INR
Viral hepatitis
IgM anti-HAV
HBsAg
IgM and IgG anti-HBc
HBV DNA a
IgG anti-HCV
HCV RNA b
IgM anti-HEV
HEV RNA
Other viral infections
IgM and IgG anti-CMV
IgM and IgG anti-HSV
IgM and IgG anti-EBV
Autoimmune hepatitis
Antinuclear antibody
Anti-liver/kidney microsomal antibody
Anti-smooth muscle antibody
Metabolic diseases
alpha-1-antitrypsin
Ceruloplasmin
Iron
Ferritin
Transferrin
Transferrin saturation
a
HBV DNA is only recommended when IgG anti-HBc is positive
b
HCV RNA is only recommended when IgG anti-HCV is positive or inconclusive 
CMV, cytomegalovirus; EBV, Epstein-Barr virus; GGT, gamma-glutamyl transferase; HAV, hepatitis A virus; 
HBc, hepatitis B core antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C 
virus; HEV, hepatitis E virus; HSV, herpes simplex virus; IgG, immunoglobulin G; IgM, immunoglobulin M; 
INR, international normalized ratio; LDH, lactate dehydrogenase.


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D 7
References
Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Case 
definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 
2011;89(6):806-15.
FDA. Guidance for Industry (issued July 2009). Drug-induced liver injury: Premarketing 
clinical evaluation. Available from: https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/drug-induced-liver-injury-premarketing-clinical-evaluation.


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Appendix E
Abbreviations
Abbreviation
or special term
Explanation
ADA
antidrug antibody
ADE
antibody-dependent enhancement
AE
adverse event
AESI
adverse event of special interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC(0-60days)
area under the concentration-time curve from time 0 to 60 days
BMI
body mass index
CDC
Centers for Disease Control and Prevention
CI
confidence interval
Cmax
maximum concentration
CoV
coronavirus
COVID-19
coronavirus disease 2019
CSP
clinical study protocol
CSR
clinical study report
DBL
database lock
DSMB
Data Safety Monitoring Board
ECG
electrocardiogram
EDC
electronic data capture
eCRF
electronic case report form
ELF
endothelial lining fluid
Fc
fragment crystallisable
FTIH
first time in human
HIV
human immunodeficiency virus
IC80
80% maximal inhibitory concentration
ICF
informed consent form
Ig
immunoglobulin
IM
intramuscular(ly)
IRT
interactive response technology
IV
intravenous(ly)
LLN
lower limit normal
mAb
monoclonal antibody


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Abbreviation
or special term
Explanation
MERS
Middle East Respiratory Syndrome
NHC
National Health Commission
NMPA
National Medical Products Administration
NOAEL
no observed adverse effect level
OTC
over-the-counter
PC
polycarbonate
PD
pharmacodynamics(s)
PE
polyethylene
PES
polyethersulfone
PK
pharmacokinetic(s)
PO
polyolefin
PP
polypropylene
PREGOUT
pregnancy outcome
PREGREP
pregnancy report
PVC
polyvinylchloride
qRT-PCR
quantitative reverse transcriptase polymerase chain reaction
QTcF
corrected QT interval by Fredericia
R0
reproduction number
RBD
receptor binding domain
RSV
respiratory syncytial virus
RTSM
Randomisation and Trial Supply Management
SAE
serious adverse event 
SAP
statistical analysis plan
SARS
severe acute respiratory syndrome
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SoA
Schedule of Activities
TBL
total bilirubin
TM
immunoglobulin constant heavy chain substitutions to modify effector function 
(L234F/L235E/P331S)
ULN
upper limit of normal
UK
United Kingdom
US
United States
w/v
weight per volume
YTE
immunoglobulin constant heavy chain substitutions to modify the half-life of the 
antibody (M252Y/S254T/T256E)


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11
REFERENCES
AstraZeneca 2021a
AstraZeneca. Update on AZD7442 STORM CHASER trial in post-exposure prevention of 
symptomatic COVID-19. Press release 15 June 2021. Available from: 
https://www.astrazeneca.com/media-centre/press-releases/2021/update-on-azd7442-storm-
chaser-trial.html. Accessed 26 August 2021.
AstraZeneca 2021b
AstraZeneca. AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in 
preventing COVID-19. Press release 20 August 2021. Available from:
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/azd7442-
prophylaxis-trial-met-primary-endpoint.html. Accessed 26 August 2021.
CIOMS 1999
Council for International Organizations of Medical Sciences (CIOMS). “5. How? – Good 
Safety Information Practising”. Guidelines For Preparing Core Clinical-Safety Information on 
Drugs Second Edition: Report of CIOMS Working Group III and V. Geneva, Switzerland: 
CIOMS, 1999, p. 36.
D’Arienzo and Coniglio 2020
D’Arienzo M, Coniglio A. Assessment of the SARS-CoV-2 basic reproduction number, R0, 
based on the early phase of COVID-19 outbreak in Italy. Biosaf Health. 2020;2(2):57-9.
ECDC 2020
European Centre for Disease Prevention and Control. Threat assessment brief: rapid increase 
of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United 
Kingdom. Available from: https://www.ecdc.europa.eu/en/publications-data/threat-
assessment-brief-rapid-increase-sars-cov-2-variant-united-kingdom. Accessed 14 February 
2021.
Furer et al 2020
Furer V, Rondaan C, Heijstek MW, Agmon-Levin N, van Assen S, Bijl M et al. 2019 Update 
of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory 
rheumatic diseases. Ann Rheum Dis. 2020;79(1):39-52.
Gonçalves et al 2020
Gonçalves A, Bertrand J, Ke R, Comets E, de Lamballerie X, Malvy D, et al. Timing of 
antiviral treatment initiation is critical to reduce SARS-CoV-2 viral load. CPT 
Pharmacometrics Syst Pharmacol. 2020;9(9):509-14.
Gorbalenya et al 2020
Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA, et al; 


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Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The 
species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and 
naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-44.
Goyal et al 2020
Goyal A, Cardozo-Ojeda EF, Schiffer JT. Potency and timing of antiviral therapy as 
determinants of duration of SARS CoV-2 shedding and intensity of inflammatory response. 
Science Advances. 2020;6(47):eabc7112.
Kim KS et al 2020
Kim KS, Ejima K, Ito Y, Iwanami S, Ohashi H, Koizumi Y, et al. Modelling SARS-Cov-2 
dynamics: implications for therapy. medRxiv 2020.03.23.20040493; 
doi:10.1101/2020.03.23.20040493.
Kim SE et al 2020
Kim SE, Jeong HS, Yu Y, Shin SU, Kim S, Oh TH, et al. Viral kinetics of Sars-Cov-2 in 
asymptomatic carriers and presymptomatic patients. Int J Infect Dis. 2020;95:441-3.
Liu et al 2020
Liu Y, Yan LM, Wan L, Xiang TX, Le A, Liu JM, et al. Viral dynamics in mild and severe 
cases of COVID-19. Lancet Infect Dis. 2020;20(6):656-7.
NHC 2021
China COVID-19 vaccinations data. Available from http://www.nhc.gov.cn. Accessed 26 July 
2021.
NMPA 2020
China Guideline for Clinical Evaluation of COVID-19 Vaccines (Draft). Available from: 
https://www.nmpa.gov.cn/yaopin/ypggtg/20200814230916157.html. Accessed 26 August 
2021.
Poland et al 2018
Poland GA, Ovsyannikova IG, Kennedy RB. Personalized vaccinology: a review. Vaccine. 
2018;36(36):5350-7.
US CDC 2021
Centers for Disease Control and Prevention. New variants of the virus that causes COVID-19. 
Available from: https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant.html. 
Accessed 18 August 2021.
Wagner and Weinberger 2020
Wagner A, Weinberger B. Vaccines to prevent infectious diseases in the older population: 
immunological challenges and future perspectives. Front Immunol. 2020;11717. WHO. WHO 
Coronavirus Disease (COVID-19) Dashboard. 2020.


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WHO 2021
WHO Coronavirus disease (COVID-19) Situation Report. Available from: 
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed 
18 August 2021.
Zimmermann and Curtis 2019
Zimmermann P, Curtis N. Factors that influence the immune response to vaccination. Clin 
Microbiol Rev. 2019;32(2).


SIGNATURE PAGE
This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic signature
Document Name: d8850c00008-csp-v2
Document Title:
D8850C00008 Clinical Study Protocol version 2
Document ID:
Version Label:
2.0 CURRENT LATEST APPROVED
Server Date
(dd-MMM-yyyy HH:mm ‘UTC’Z)
Signed by
Meaning of Signature
02-Sep-2021 17:01 UTC
Content Approval
01-Sep-2021 16:00 UTC
Content Approval
02-Sep-2021 02:11 UTC
Content Approval
02-Sep-2021 14:52 UTC
Content Approval
Notes: (1) Document details as stored in ANGEL, an AstraZeneca document management system.
PPD
PPD
PPD
PPD
PPD

SAP_001.pdf: 
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STATISTICAL ANALYSIS PLAN
Study Code
D8850C00008
Edition Number
2.0
Date
16-Sep-2022
A Phase II Double-blind, Placebo-controlled Study to Evaluate 
the Safety and Tolerability of AZD7442 in Chinese Adults


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TABLE OF CONTENTS
TITLE PAGE................................................................................................................1
TABLE OF CONTENTS..............................................................................................2
LIST OF ABBREVIATIONS .......................................................................................4
AMENDMENT HISTORY...........................................................................................6
1
INTRODUCTION......................................................................................7
2
CHANGES TO PROTOCOL PLANNED ANALYSES..............................7
3
DATA ANALYSIS CONSIDERATIONS ..................................................7
3.1
Timing of Analyses.....................................................................................7
3.2
Analysis Populations...................................................................................7
3.3
General Considerations...............................................................................8
3.3.1
General Study Level Definitions ...............................................................10
3.3.1.1
Study Period .............................................................................................10
3.3.1.2
Reference Start Date and Study Day .........................................................10
3.3.1.3
Baseline Definition and Change from Baseline .........................................10
3.3.2
Visit Window ...........................................................................................11
3.3.3
Handling of Unscheduled Visits................................................................14
3.3.4
Multiplicity/Multiple Comparisons ...........................................................14
3.3.5
Handling of Protocol Deviations in Study Analysis...................................14
3.3.6
Handling of Missing data..........................................................................15
3.3.6.1
Imputation of Missing Date about Prior/Concomitant Medications ...........15
3.3.6.2
Imputation of  Missing Information related to AE.....................................15
3.3.6.3
Imputation for PK, PD and ADA Endpoints..............................................15
4
STATISTICAL ANALYSIS.....................................................................15
4.1
Study Population.......................................................................................15
4.1.1
Subject Disposition and Completion Status...............................................15
4.1.2
Analysis Sets ............................................................................................16
4.1.3
Protocol Deviations...................................................................................16
4.1.4
Demographics...........................................................................................16
4.1.4.1
Definitions and Derivations ......................................................................16
4.1.5
Baseline Characteristics............................................................................17
4.1.6
Disease Characteristics .............................................................................17
4.1.7
Medical/Surgical History and Concomitant Disease..................................17
4.1.8
Prior and Concomitant Medications ..........................................................17
4.1.9
Study Drug Compliance............................................................................18
4.2
Safety and Tolerability..............................................................................18
4.2.1
Exposure...................................................................................................18
4.2.2
Adverse Events.........................................................................................19
4.2.2.1
Definitions................................................................................................19
4.2.2.2
Analysis and Presentation .........................................................................19
4.2.3
Clinical Laboratory...................................................................................20


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4.2.4
Vital Signs................................................................................................21
4.2.5
Electrocardiogram.....................................................................................22
4.2.6
Other Safety Assessments.........................................................................23
4.3
Pharmacokinetics......................................................................................23
4.3.1
Serum Concentration ................................................................................23
4.3.1.1
Handling Rule for BLQ Serum Concentrations .........................................23
4.3.1.2
Presentation of PK Concentration .............................................................24
4.3.2
PK Parameters ..........................................................................................25
4.3.2.1
Derivation of PK Parameters.....................................................................25
4.3.2.2
Presentation of PK Parameters..................................................................26
4.4
Immunogenicity........................................................................................26
4.4.1
ADA Definitions.......................................................................................27
4.4.2
Handling Rule for Negative or Borderline ADA data................................29
4.4.3
ADA Analysis and Presentation................................................................29
4.5
Pharmacodynamics...................................................................................30
4.5.1
Serum Neutralising Responses Against SARS-CoV-2...............................30
4.5.1.1
Handling Rule for Unquantifiable Neutralizing Titer.................................30
4.5.1.2
Analysis and Presentation .........................................................................30
4.6
Other Exploratory Analyses......................................................................31
4.6.1
SARS-CoV-2 qRT-PCR Test....................................................................31
4.6.2
SARS-CoV-2 Serology Test .....................................................................31
5
INTERIM ANALYSIS .............................................................................32
6
REFERENCES.........................................................................................32
7
APPENDIX ..............................................................................................32
APPENDIX 1. Date Conventions for Prior/Concomitant Medications.........................32
LIST OF TABLES
Table 1 Analysis windows for SARS-CoV-2 serology testing by visit.........................11
Table 2 Analysis windows for serum PK concentration by visit ..................................12
Table 3 Analysis windows for serum ADA assessment by visit...................................12
Table 4 Analysis windows for serum SARS-CoV-2 nAbs assessment by visit.............12
Table 5 Analysis windows for vital signs ....................................................................13
Table 6 Analysis windows for ECG ............................................................................13
Table 7 Analysis windows for clinical laboratory by visit ...........................................14
Table 8 Vital sign reference ranges .............................................................................21
Table 9 Key PK Parameters ........................................................................................25
Table 10 PK Diagnostic Parameters ............................................................................25


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LIST OF ABBREVIATIONS
Abbreviation or 
Specialized 
Term
Definition
ADA
Anti-drug antibodies
AE
Adverse event
AESI
adverse event of special interest
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BLQ
Below the lower limit of quantification
BMI
Body mass index
CI
Confidence interval
CRF
Case report form
CSP
Clinical study protocol
CSR
Clinical study report
CV
Coefficient of variation
DSMB
Data Safety Monitoring Board
ECG
Electrocardiogram
gSD
Geometric standard deviation
IC80
80% maximal inhibitory concentration
ICF
Informed consent form
IP
Investigational Product
IPD
Important protocol deviation
IV
Intravenous
LLOQ
Lower limit of quantification
LOD
Limit of detection
mAb
Monoclonal antibody
MedDRA
Medical dictionary for regulatory activities
NC
Not calculated
NR
Not reportable
NS
No sample
NQ
Not quantifiable
PD
Pharmacodynamic
PK
Pharmacokinetics
PT
Preferred term
qRT-PCR
Quantitative reverse transcriptase polymerase chain reaction


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SAE
Serious adverse event
SAP
Statistical analysis plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SD
Standard deviation
SI
Standard international
SoA
Schedule of activities
SoC
System organ class
ULOQ
Upper limit of quantification


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AMENDMENT HISTORY
CATEGORY
Change refers to:
Date
Description of change
In line with CSP?
Rationale
N/A
1/17/2022
Initial approved SAP
N/A
N/A
Data presentation
8/26/2022
Section 3.3.2: clarified target 
time can be considered as 
reference if time is collected.
Yes
To provide additional clarification 
Data presentation
8/26/2022
Section 3.3.2: removed early 
discontinuation visit (EDV) 
from the analysis window as 
EDV will not be presented in 
summary tables
Yes
To provide additional clarification
Data presentation
8/26/2022
Section 4.2.2.2: added any IP 
related AESI to the AE 
overview; also added a 
summary table for most 
common adverse events.
Yes
Any IP related AESI and most 
common AE will assist safety 
evaluation by local team.
Data presentation
8/26/2022
Section 4.2.3: added that 
selected chemistry tests will 
also be presented in original 
units.
Yes
Original units for selected chemistry 
tests will assist safety review by 
local team.
Data presentation
8/26/2022
Section 4.2.3: provided 
reference ranges for lab tests 
International Normalized 
Ratio and Direct Bilirubin
Yes
Due to vendor system set-up, 
reference ranges for 2 lab tests 
could not be applied or transferred. 
Pre-specified reference ranges will 
be used in safety evaluation.
Data presentation
8/26/2022
Section 4.3.1.1: clarified 
how to present summary 
statistics when only one 
observation is ≥ LLOQ
Yes
To provide additional clarification


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1
INTRODUCTION
This is the statistical analysis plan (SAP) for study D8850C00008 and outlines the analyses 
to be generated for the clinical study report (CSR). The SAP describes the statistical 
analyses specified in the latest version of the clinical study protocol (CSP) in more detail. 
Any changes to what is specified in the CSP will be described. 
2
CHANGES TO PROTOCOL PLANNED ANALYSES
In addition to ADA analysis set, clarifications were provided to AZD1061 ADA evaluable 
analysis set, AZD8895 ADA evaluable analysis set, and AZD7442 ADA evaluable analysis 
set.
3
DATA ANALYSIS CONSIDERATIONS
3.1
Timing of Analyses
The primary DBL will occur after all treated participants have completed (or withdrawn
from) follow-up through Day 181 to conduct the primary analysis. All available data 
(before the data cut-off date) at the time of DBL will be included in the primary analysis. 
No early stopping decision will be made for futility or superiority at the primary analysis.
All participants in the study will be assessed for safety and tolerability, PK, and PD for 
approximately 15 months following the first dose of study intervention (through Day 451). 
A final DBL will occur when all participants have completed (or withdrawn from) the 
study.
As safety evaluation is the primary objective and no multiplicity control is applied, ad-hoc 
interim analyses may be performed for additional evaluation (e.g. potential safety signal).
3.2
Analysis Populations
All participants analysis set: All participants who signed the ICF.
Randomised analysis set: All participants who were randomised in the study.
Full analysis set: All randomised participants who received any amount of AZD7442 or 
placebo, irrespective of their protocol adherence and continued participation in the study.
Participants will be analysed according to their randomised treatment, irrespective of 
whether or not they have prematurely discontinued, according to the intent-to-treat 
principle. Participants who withdraw consent to participate in the study will be included up 
to the date of their study termination
Safety analysis set: All participants who received any amount of AZD7442 or placebo.


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Erroneously treated participants (eg, those randomised to intervention A but actually given 
intervention B) will be analysed according to the intervention they actually receive.
PK analysis set: All participants in the safety analysis set who received AZD7442 and had 
at least one quantifiable serum PK observation post-dose, with no important protocol 
deviations thought to impact the analysis of the PK data.
ADA analysis set: All participants in the safety analysis set who received any amount of 
AZD7442 or placebo and had a non-missing baseline ADA result and at least one 
non-missing post-baseline ADA result. More specifically, 
!
AZD1061 ADA evaluable analysis set consists of participants in the safety 
analysis set who have a non-missing baseline AZD1061 ADA result and at least one 
non-missing post-baseline AZD1061 ADA result.
!
AZD8895 ADA evaluable analysis set consists of participants in the safety 
analysis set who have a non-missing baseline AZD8895 ADA result and at least one 
non-missing post-baseline AZD8895 ADA result.
!
AZD7442 ADA evaluable analysis set consists of participants in the safety 
analysis set who are AZD8895 ADA evaluable and/or AZD1061 ADA evaluable.
PD analysis set: All participants in the safety analysis set who received AZD7442 or 
placebo and had at least one quantifiable titer observation post-dose, with no important 
protocol deviations thought to impact the analysis of the PD data.
Participant disposition will be reported using the all participants analysis set. 
Pharmacokinetics will be assessed using the PK analysis set. Pharmacodynamics will be 
assessed using the PD analysis set. Exploratory efficacy endpoints will be assessed using 
the full analysis set. Immunogenicity will be assessed using the respective ADA evaluable 
analysis set for AZD1061, AZD8895, and AZD7442. All remaining evaluations including 
safety analysis will use the safety analysis set, unless otherwise stated.
3.3
General Considerations
In general, the as-treated principle will be applied to study evaluations, which is 
participants who received study intervention other than the one assigned by randomisation 
will be analysed as belonging to the actual intervention received.
Unless otherwise noted, all data will be presented by intervention group (i.e. AZD7442 600 
mg IV and placebo) using descriptive statistics. Selected outputs may be repeated by 
stratification factors 
 and v
 as appropriate.
CCI
CCI


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The following general principles will be followed throughout the study:
!
Categorical variables will be summarised using frequency and percentages, where the 
denominator for calculation is the underlying analysis set population, unless otherwise 
stated. Percentages will be rounded to 1 decimal place. Rounding will be applied, 
except for percentages < 0.1 but > 0.0 which will be presented as ‘< 0.1’ and 
percentages < 100.0 but >99.9 which will be presented as ‘>99.9’. Percentage for 100 is 
presented as 100 with no decimal. Percentages for 0 will not be presented.
!
Continuous variables will be summarised with descriptive statistics including number 
of available observations (n), mean, standard deviation (SD), median, minimum, 
maximum, and quartiles as appropriate. The minimum and maximum will be reported 
to the same number of decimal places as the raw data recorded in the database, and the 
mean, median, lower quartile, upper quartile and SD will be reported to one more 
decimal place than the raw data recorded in the database, unless specified otherwise. In 
general, the maximum number of decimal places reported shall be 4 for any summary 
statistics.
!
PK concentration data will be summarised using descriptive statistics, including n, n of 
BLQ, geometric mean, geometric coefficient of variation CV%, arithmetic mean, SD, 
minimum, median, and maximum values. Geometric mean, geometric SD and 
geometric CV% are calculated based on the log-transformed data. Geometric mean is 
the back-transformed mean of the log-transformed values and geometric SD is the 
back-transformed SD of the log-transformed values.
gMean = exp(
	(
)  	(
)  …  	(
)
	
)
gSD = exp(SD(ln(y1),…,ln(yn)))
Geometric CV (%) = 100 ∗exp Varln(y), … , ln(y	) ! −1
  = 100 ∗exp #$ln(y), … , ln(y	) 
%! −1
   = 100 ∗&exp((ln('#$))%) −1
!
All PK parameters will be listed and summarised using the same descriptive statistics 
as for PK concentrations, with the exception that for tlast, only n, median, minimum 
and maximum will be reported.
!
In general, PK concentration will be listed to the same number of significant figures as 
received from the bioanalytical laboratory (usually but not always to 3 significant 
figures). In general, descriptive statistics for PK concentration are presented to 4 
significant figures with the exception of the min and max which are presented to 3 
significant figures, while n and n of BLQ will be presented as integers. Descriptive 


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statistics for PK parameters are generally presented to 4 significant figures.
Pharmacokinetic parameters will be derived using non-compartmental analysis methods 
with Phoenix® WinNonlin® version 8.1 or higher. All descriptive and inferential statistical 
computations will be performed using SAS® version 9.4, or higher.
3.3.1
General Study Level Definitions
3.3.1.1
Study Period
The study consists of 3 periods:
Screening period: Days -28 through -1 (up to 28 days), 
Intervention period: Day 1, randomisation and dosing,
Safety follow-up period: Days 2 through 451 (450 days). 
A participant is considered to have completed the study if he/she has completed all periods 
of the study including the last scheduled procedure shown in the SoA specified in CSP 
Section 1.3.
The end of the study is defined as the date of the last scheduled procedure shown in the 
SoA specified in CSP Section 1.3 for the last participant in the study.
3.3.1.2
Reference Start Date and Study Day
Study day will be calculated from the reference start date and will be used to show 
start/stop day of assessments and events. Reference start date is defined as the date of the 
first dose of study intervention i.e. Day 1.
Study day will be computed as follows:
!
Study Day = date of event – date of 1st dose of study intervention + 1, if the date of 
event is on or after the date of 1st dose of study intervention.
!
Study Day = date of event – date of 1st dose of study intervention, if the date of event is 
prior to the date of 1st dose of study intervention.
3.3.1.3
Baseline Definition and Change from Baseline
In general, the last available measurement prior to the first dose of study intervention will 
serve as the baseline. If there is no result collected prior to the first dose, then baseline 
value will be set to missing and will not be imputed, unless otherwise specified. In the case 
where the last non-missing measurement and the date and time of the dose of study 
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baseline, but adverse events commencing on the date and time of the dose of study 
intervention will be considered post-baseline.
Change from baseline = post-baseline value – baseline value
If either the post baseline value or the baseline value is missing, then the absolute change 
from baseline value will also be set to missing.
3.3.2
Visit Window
Visit windows will be used for all protocol-specified assessments to allow for by-visit 
analyses, since not all assessments are performed on the scheduled day. Unless specified 
otherwise, all safety, pharmacokinetic, pharmacodynamic and immunogenicity analyses 
will be based on the analysis visit windows. The actual assessment from scheduled and/or 
unscheduled day will be mapped to the planned study visit following the analysis visit 
windowing rules below:
!
If more than one assessment falls within a visit window, the closest non-missing 
assessment to the target day (or target time if assessment time available) will be 
used in the analysis.
!
If actual dates (or datetimes) of two non-missing assessments are equidistant from 
the target day (or target time if assessment time available), the later visit will be 
used in the analysis.
!
If actual dates (or datetimes) of two non-missing assessments are at the same date 
without time information, the assessment with worst result will be used for 
categorical variables and the mean will be used for continuous variables in the 
analysis.
The visit windows will be calculated by bisecting the scheduled visit days. The lower 
limit of each window will be the mean of the 2 adjacent planned study days, rounded up 
to the nearest integer. The upper limit of each window will be the mean of the 2 
adjacent planned study days, rounded down to the nearest integer.
Table 1 Analysis windows for SARS-CoV-2 serology testing by visit
Prorocol 
Visit
Target 
Day 
Analysis 
Visit
Analysis Window (Study Day)
Visit 2
1 (pre-dose)
Baseline
All assessments prior to the start of 
infusion.


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Visit 7
181
Day 181
All assessments after the start of first 
administration of investigational 
product to 270
Visit 9
361
Day 361
>=271
Table 2 Analysis windows for serum PK concentration by visit
Protocol 
Visit
Target Day
Analysis Visit
Analysis Window (Study Day)
Visit 2
1 (pre-dose)
Baseline
All assessments prior to the start 
of infusion
Visit 2
1 (post-dose)
Day 1, End of 
Infusion 
start of infusion to day 4
Visit 3
8
Day 8
5 to 19
Visit 4
31
Day 31
20 to 45
Visit 5
61
Day 61
46 to 75
Visit 6
91
Day 91
76 to 135
Visit 7
181
Day 181
136 to 225
Visit 8
271
Day 271
226 to 315
Visit 9
361
Day 361
>=316
Table 3 Analysis windows for serum ADA assessment by visit
Protocol 
Visit
Target 
Day
Analysis 
Visit
Analysis Window (Study Day)
Visit 2
1 (pre-dose)
Baseline
All assessments prior to the start of 
infusion. 
Visit 4
31
Day 31
Start of infusion to day 60
Visit 6
91
Day 91
61 to 135
Visit 7
181
Day 181
136 to 270
Visit 9
361
Day 361
>=271 
Table 4 Analysis windows for serum SARS-CoV-2 nAbs assessment by visit
Protocol 
Visit 
Target 
Day
Analysis 
Visit
Analysis Window (Study Day)
Visit 2
1 (pre-dose)
Baseline
All assessments prior to the start of 
infusion
Visit 3
8
Day 8
Start of infusion to 19


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Visit 4
31
Day 31
20 to 45
Visit 5
61
Day 61
46 to 75
Visit 6
91
Day 91
76 to 135
Visit 7
181
Day 181
136 to 225
Visit 8
271
Day 271
226 to 315
Visit 9
361
Day 361
>=316
Table 5 Analysis windows for vital signs
Protocol 
Visit
Target Day
Analysis Visit
Analysis Window (Study Day)
Visit 2
1 (pre-dose)
Baseline
All assessments prior to the start 
of infusion
Visit 2
1 (post-dose)
Day 1, end of 
infusion
Start of infusion to 15 mins after 
infusion completed
Visit 2
1 (post-dose)
Day 1, 30 mins post-
dose
16 mins to 45 mins after infusion 
completed
Visit 2
1 (post-dose)
Day 1, 60 mins post-
dose
46 mins to 75 mins after infusion 
completed
Visit 2
1 (post-dose)
Day 1, 90 mins post-
dose
76 mins to 105 mins after infusion 
completed
Visit 2
1 (post-dose)
Day 1, 120 mins 
post-dose
106 mins after infusion completed 
to day 4
Visit 3
8
Day 8
5 to 19
Visit 4
31
Day 31
20 to 45
Visit 5
61
Day 61
46 to 75
Visit 6
91
Day 91
76 to 135
Visit 7
181
Day 181
136 to 225
Visit 8
271
Day 271
226 to 315
Visit 9
361
Day 361
>=316
Table 6 Analysis windows for ECG 
Protocol 
Visit
Target 
Day
Analysis Visit
Analysis Window (Study Day)
Visit 1
Day -28 to 
Day -1
Baseline
All assessments prior to the start of 
infusion
Visit 4
31
Day 31
Start of infusion to day 105
Visit 7
181
Day 181
106 to 270


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Visit 9
361
Day 361
>=271
Table 7 Analysis windows for clinical laboratory by visit
Protocol 
Visit
Target 
Day
Analysis Visit
Analysis Window (Study Day)
Visit 2
1(pre-dose)
Baseline
All assessments prior to start of 
infusion
Visit 3
8
Day 8
Start of infusion to 19
Visit 4
31
Day 31
20 to 105
Visit 7
181
Day 181
106 to 270
Visit 9
361
Day 361
>=271
3.3.3
Handling of Unscheduled Visits 
Measurements collected from unscheduled visits or early study discontinuation visits may 
also be considered in the analysis visit window. In the case of a missing value at a 
scheduled visit, which is then followed by a non-missing value at an unscheduled 
assessment within the same visit window, the non-missing value at the unscheduled 
assessment will be used. Data collected at unscheduled assessments might be included in 
baseline definitions, and in any definitions of maximum value, minimum value where 
appropriate.
3.3.4
Multiplicity/Multiple Comparisons
No statistical hypotheses will be evaluated based on formal statistical tests. Consequently, 
no correction for multiplicity will be used.
3.3.5
Handling of Protocol Deviations in Study Analysis
An IPD, per ICH definition is “a subset of protocol deviations that may significantly impact 
the completeness, accuracy, and/or reliability of the study data or that may significantly 
affect a participant’s rights, safety, or wellbeing.”
The study specific IPDs are provided and classified in the AstraZeneca Protocol Deviation 
Plan. The IPDs include but are not limited to Inclusion/Exclusion Criteria Deviations, 
Investigational Product Deviations, Excluded Medications taken, and Deviations to study 
procedure. Refer to PD Plan document for all details of IPD. 
Additionally, all protocol deviations and issues related to COVID-19 (such as missed visit, 
procedure not performed at visit etc.) will be captured for reporting.


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3.3.6
Handling of Missing data
3.3.6.1
Imputation of Missing Date about Prior/Concomitant Medications
Partial or completely missing dates of prior and/or concomitant medications will be handled 
as described in APPENDIX 1.
3.3.6.2
Imputation of  Missing Information related to AE 
For purpose of the AE summaries, the following will apply:
• AEs with unknown intensity will be treated as “severe” for the tabulations.
• AEs with unknown relationship will be treated as “related” for the tabulations.
• AEs with unknown seriousness will be treated as “serious” for the tabulations.
• AE with a (complete or partial) missing onset date will be treated as post dose and will be 
presented in AE summaries, unless the stop date (or partial onset date) indicates otherwise.
There will be no imputation of AE data for the data listings and key subject information.
3.3.6.3
Imputation for PK, PD and ADA Endpoints
Serum PK concentration that are Not Quantifiable (NQ), Not Reportable (NR), or No 
Sample (NS) will be handled as described in Section 4.3.1.1.
ADA titer values below the minimum required dilution (MRD) will be handled as 
described in Section 4.4.2.
For neutralizing antibody against SARS-CoV-2, titer values below the lower limit of 
quantification (LLOQ) or above the upper limit of quantification (ULOQ) will be handled 
as described in Section 4.5.1.1.
4
STATISTICAL ANALYSIS
4.1
Study Population
This section will cover subject disposition, analysis sets, protocol deviations, demographics 
and baseline characteristics, prior and concomitant medication, and medical/surgical 
history. 
4.1.1
Subject Disposition and Completion Status
Number and percentage of participants in the following categories will be presented in a 
summary table for each intervention group (i.e. AZD7442 600 mg IV and placebo) and 
study total: participants enrolled, screen failures, participants randomized, participants not 
randomized (including reasons), participants who received any dose of study intervention, 


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participants who did not receive treatment (including reasons), participants with on-going 
study follow-up, participants who completed the study, participants discontinued from 
study (including reasons), participants who became unblinded (including reasons). 
Separate listings including all standardized disposition terms will be also provided for 
participants who were discontinued from the study as well as for participants who 
completed the study.
Randomization code and actual kit numbers used will also be listed. 
The number and percentage of participants with one or more disruption(s) due to COVID-
19 pandemic will be presented by intervention group (i.e. AZD7442 600 mg IV and 
placebo) and study total. A listing of all participants affected by the COVID-19 related 
study disruption will be produced. COVID-19 related study disruptions may include:
!
Visit related (if a study visit is impacted by global/country situation, then contact mode 
will be specified); 
!
Study intervention related;
!
Withdrawal from study (if primary reason for ending study is related to global/country 
situation). 
4.1.2
Analysis Sets
See section 3.2 for the definitions of analysis set.
The number of participants belonging to each analysis set will be presented in a summary 
table by intervention group (i.e. AZD7442 600 mg IV and placebo) and study total.
Listing of all participants excluded from any analysis set and reason for exclusion from 
respective analysis set will also be provided.
4.1.3
Protocol Deviations
The number and percentage of participants with at least one IPD, including COVID-19 
related IPD, will be summarised following categories specified in Protocol Deviation Plan, 
for each intervention group and study total based on the Safety Analysis Set. 
All COVID-19 related issues regardless of whether the issue is considered as a protocol 
deviation or not, will be listed separately.
4.1.4
Demographics
4.1.4.1
Definitions and Derivations
Demographics includes but is not limited to age, sex, race and ethnic group. 


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All demographic data will be summarized using descriptive statistics based on the Safety 
Analysis Set for each intervention group and study total. Age will be summarised as a 
continuous variable and also as a categorical variable (i.e. 
).
All demographic data will be listed based on the Safety Analysis Set.
4.1.5
Baseline Characteristics
Baseline characteristics includes but is not limited to height (cm), weight (kg), body mass 
index (BMI) (kg/m²), COVID-19 vaccination status (i.e. yes, no). 
BMI (kg/m²) will be calculated from the height (in meters) and weight (in kilograms) as 
follows: BMI = weight / (height^2). 
All baseline characteristics data will be summarized using descriptive statistics based on the 
Safety Analysis Set for each intervention group and study total. 
All baseline characteristics will be listed based on the Safety Analysis Set.
4.1.6
Disease Characteristics
Study population includes healthy participants as well as participants with stable medical 
conditions. For participants with stable medical conditions, their concomitant disease will 
be collected as an on-going condition in medical history. Details will be discussed in 
Section 4.1.7.
4.1.7
Medical/Surgical History and Concomitant Disease
Medical/Surgical history will be coded in Medical Dictionary for Regulatory Activities 
(MedDRA) version 24.0 or higher .
Medical history will be presented descriptively by System Organ Class (SOC) and 
Preferred Term (PT) for each intervention group and study total. Number and percentages 
of participants by each SOC/PT will be summarized based on the Safety Analysis Set.
Surgical history will be presented similarly in a separate table.
4.1.8
Prior and Concomitant Medications
The WHO-DD March 2021 B3 Global or higher is used to classify medications by WHO 
Anatomical Therapeutic Chemical (ATC) classification of ingredients.
Prior medications are defined as any medication that started and stopped prior to enrolment 
(exclusive). 
Concomitant medications are defined as:
CCI


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!
any medication that started on or after enrolment;
!
any medication that started before enrolment AND was ongoing at the time of 
enrolment or ended on the enrolment date
Medications with completely missing stop date are classified as concomitant. Handling 
method of partial/complete missing date about prior/concomitant medications is described 
in Section 3.3.6.1. Medications will be classified as either prior or concomitant (but not 
both) accordingly.
The number and percentage of participants receiving prior or concomitant medication,
including COVID-19 vaccine, will be presented by intervention group and study total using 
the Safety Analysis Set. 
All medications will also be listed.
4.1.9
Study Drug Compliance
Compliance will not be calculated as this is a single dose study. Dose administration details 
such as whether a participant completed study intervention per protocol will be presented as 
exposure, which is discussed in Section 4.2.1.
4.2
Safety and Tolerability
The study primary objective is to evaluate the safety and tolerability of a single dose of 
600 mg AZD7442 administered IV among Chinese participants (including those with stable 
medical conditions). Safety assessments, including AEs, SAEs, AESIs, safety laboratory 
parameters (haematology, clinical chemistry, coagulation, and urinalysis); 12-lead ECG; 
vital signs (blood pressure, pulse rate, body temperature, and respiratory rate) will be 
presented based on Safety Analysis Set.
4.2.1
Exposure
Exposure for the following categories will be summarised descriptively with the number 
and percentages of participants in Safety Analysis Set: number of participants received 
administration, administration per protocol (Yes/No), and if not per protocol, reasons and 
action taken.
Exposure details, such as administration date and time, will be listed based on Safety 
Analysis Set. 


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4.2.2
Adverse Events
4.2.2.1
Definitions
Definitions of an AE or SAE can be found in Appendix B of the study protocol. Adverse 
Events of Special Interest (AESIs) is defined in section 8.3.4 of the study protocol. 
The AESIs for AZD7442 include:
!
Anaphylaxis and other serious hypersensitivity reactions, including immune complex 
disease
!
Infusion-related reactions 
AEs and SAEs will be collected from the time of signing the informed consent form 
throughout the study up to and including the last visit. AEs and SAEs with an onset 
date/time >= date/time of dosing will be summarized by actual intervention group based on 
Safety Analysis Set. AEs will be coded with MedDRA version 24.0 or higher.
4.2.2.2
Analysis and Presentation
An overview of AEs will be presented by actual intervention group and study total based on 
Safety Analysis Set. It will summarize the number and percentage of participants reporting 
at least one event (i.e., multiple occurrences of an AE for a participant will only be counted 
once) and number of events where appropriate (i.e., accounting for multiple occurrences of 
the same event in a participant) for the following categories:
!
Any AE
!
Any SAE
!
Any SAE with outcome death 
!
Any AE leading to discontinuation of IP
!
Any AE leading to dose interruption 
!
Any AE leading to withdrawal from study
!
Any AESI
!
Any IP related AE
!
Any IP related SAE
!
Any IP related AESI
AE overview may be repeated by 
 and 
 as 
appropriate.
Adverse events, AEs with outcome of death, SAEs and AE leading to IP
discontinuation/interruption will be summarised by SOC, and PT assigned to the event by 
MedDRA.  For each PT, the number and percentage of patients reporting at least one 
CCI
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occurrence will be presented, i.e., for a patient multiple occurrences of an AE will only be 
counted once. 
A summary of all AEs will be presented by PT. Most common adverse events (frequency of 
>5% in any treatment group) as well as AESI will also be summarised by PT.  Summary of 
AEs will be broken down further by investigator’s causality assessment (related vs not 
related) and maximum intensity. If a patient reports multiple occurrences of the same AE 
within the same study period, the maximum intensity will be taken as the highest recorded 
maximum intensity (the order being mild, moderate, and severe).  
Details of all AEs and SAEs, including those reported during screening, will be listed based 
on the Safety Analysis Set.
4.2.3
Clinical Laboratory
Chemistry, haematology, coagulation, and urinalysis will be taken at scheduled visits 
indicated in the SoA (Section 1.3) of CSP. Safety laboratory assessments are defined in the 
CSP Table 12 in section 8.2.4.
Quantitative laboratory parameters reported as “< X”, i.e. below the lower limit of 
quantification or “> X”, i.e. above the upper limit of quantification, will be converted to X 
for the purpose of quantitative summaries, but will be presented as recorded, i.e. as “< X” 
or “> X” in the listings.
The following summaries will be provided by actual intervention group based on the Safety 
Analysis Set for each of chemistry, haematology, coagulation, and urinalysis laboratory 
parameter where appropriate:
!
Observed and change from baseline in Standard International (SI) units by visit (for 
quantitative parameters). Additionally, some chemistry assessments including alanine 
aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline 
phosphatase, and creatine kinase will also be presented in original units.
!
Number and percentage of participants in each laboratory parameter category by visit 
(for categorical parameters)
!
Shift tables from baseline to the maximum and/or minimum post-baseline observed 
value according to normal range criteria (e.g., low, normal, high)
In addition, the post-baseline maximum of ALT and AST by the post-baseline maximum of 
total bilirubin may be presented as appropriate. 
All clinical laboratory data will be listed.


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Note: During the study blinded data review before the clinical database lock , a data 
transfer issue was identified that the reference range for International Normalized Ratio and 
Direct Bilirubin were not applied in vendor database set-up. The following reference ranges 
will be pre-specified and used in safety evaluation:
!
International Normalized Ratio: 
─Patient not taking oral anticoagulant: 0.8 - 1.2
─Patient taking oral anticoagulant: 2.0 - 3.0
!
Direct Bilirubin: 0-0.4 mg/dL
4.2.4
Vital Signs
Vital signs assessments (body temperature, diastolic blood pressure (DBP), systolic blood 
pressure (SBP), pulse rate and respiratory rate) will be performed at the visits indicated in 
the SoA (Section 1.3) of CSP. 
Additionally, vital sign values will be classified as normal (between the lower and upper 
limits), low (below the lower limit), and high (above the upper limit) according to the 
reference ranges:
Table 8 Vital sign reference ranges 
Parameter
Standard Unit
Lower limit
Upper limit
Body temperature
°C
37.8
DBP
mmHg
60
90 
SBP
mmHg
90
140 
Pulse rate
beats/min
60
100
Respiratory rate
breath/min
12
20
The following summaries will be provided by actual intervention group based on the Safety 
Analysis Set where appropriate:
!
Observed values and change from baseline in vital sign parameters by visit;
!
Shift tables from baseline to the maximum and/or minimum post-baseline observed 
value according to reference range (e.g., low, normal, high)
All vital sign data will be listed, and vital sign status compared to the reference range (low, 
normal, high) will be indicated.


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4.2.5
Electrocardiogram
Twelve-lead electrocardiogram (ECG) will be performed at timepoints as specified in the 
SoA (Section 1.3) of CSP. The following ECG variables will be collected:
!
Heart rate (bpm)
!
PR interval (msec)
!
RR interval (msec)
!
QRS duration (msec)
!
QT interval (msec)
!
QTcF interval (msec)
!
Overall ECG interpretation (Investigator’s judgement)
∀
Normal
∀
Abnormal, not clinically significant
∀
Abnormal, clinical significant
Markedly abnormal quantitative ECG parameters will be identified in accordance with the 
following predefined markedly abnormal criteria:
!
Observed values for QTcF interval will be classified as:
∀
> 450 msec;
∀
> 480 msec;
∀
> 500 msec
!
Change from baseline for QTcF interval will be classified as:
∀
>30 msec increase from baseline
∀
>60 msec increase from baseline
It is to be noted that the previous categories are not mutually exclusive, but cumulative. For 
example, if a participant’s worst post-baseline QTcF post-baseline observed value is 490 
mmHg, then this participant will be reported once under QTcF > 450 msec and once under 
QTcF > 480 msec.
The following summaries will be provided by actual intervention group based on the Safety 
Analysis Set for ECG parameters where appropriate:
!
Observed and change from baseline by visit (for quantitative parameters);
!
A shift table of categorical ECG interpretation (from best to worst: normal, abnormal -
not clinically significant, abnormal - clinically significant) at baseline versus worst 
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!
Number and percentages of participants with at least one markedly abnormal post-
baseline observed.
Individual ECG results and abnormalities in ECG will be listed.
4.2.6
Other Safety Assessments
Other assessments such as Pregnancy Testing will be listed where appropriate.
4.3
Pharmacokinetics
One of the study secondary objectives is to evaluate pharmacokinetics of AZD8895,
AZD1061, and AZD7442 after a single dose of 600 mg AZD7442 IV. 
Serum samples will be collected for measurements of AZD8895 and AZD1061
concentrations as well as AZD7442 concentration (i.e. sum of AZD8895 and AZD1061) at 
time points specified in the SoA (Section 1.3) of CSP. 
PK analyses will be based on the PK Analysis Set, and may be repeated by 
 
 and 
 
as appropriate. Any PK data excluded from summary tables or mean plots 
will be flagged in participant listing.
4.3.1
Serum Concentration
Serum PK concentrations of each mAb (AZD8895 and AZD1061) and AZD7442 (i.e. sum 
of AZD8895 and AZD1061) will be listed and tabulated as appropriate.
4.3.1.1
Handling Rule for BLQ Serum Concentrations
Serum concentrations that are below the LLOQ (i.e. Not Quantifiable [NQ]), or reported as 
NR (Not Reportable) or NS (No Sample) will be handled as follows for the provision of 
descriptive statistics:
!
Any values reported as NR or NS will be excluded from the summary tables and 
corresponding figures.
!
At a time point where less than or equal to 50% of the concentration values are NQ, all 
NQ values will be set to the LLOQ, and all descriptive statistics will be calculated 
accordingly.
!
At a time point where more than 50% (but not all) of the values are NQ, the gmean, 
gSD, gCV%, arithmetic mean and SD will be set to NC (Not Calculated). The 
maximum value will be reported from the individual data, and the minimum and 
median will be set to NQ.
CCI
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!
If all concentrations are NQ at a time point, no descriptive statistics will be calculated 
for that time point. The gmean, arithmetic mean, minimum, median and maximum will 
be reported as NQ, and the gCV%, gSD and SD will be reported as NC.
!
The number of values below LLOQ will be reported for each time point together with 
the total number of collected values (n).
Three observations ≥ LLOQ are required as a minimum for a serum concentration or PK 
parameter (e.g. Cmax, Cmin, Clast) to be summarized. When only one or two observations 
≥ LLOQ , minimum and maximum will be presented , and will be presented as the only 
available value in case of one observation ≥ LLOQ, with the other summary statistics as 
NC.
For mean figures, concentrations that are NQ will be handled as described for the 
descriptive statistics. If this handling results in a geometric mean of “NQ”, then the value 
plotted at that time point will be set to missing for both linear and semi-logarithmic plots.
For individual figures, concentrations that are NQ will be regarded as missing, with the 
exception that NQ prior to the first quantifiable sample should all be set to 0 (linear scale).
4.3.1.2
Presentation of PK Concentration
The PK concentrations will be summarized in tabular and graphical forms, as appropriate, 
according to the latest version of the AstraZeneca standards.
Serum concentrations for each scheduled time point will be summarized for each mAb 
component and AZD7442 based on the PK Analyses Set using the following descriptive 
statistics: number of participants included in analysis (n), n below lower limit of 
quantification (LLOQ), arithmetic mean, SD, geometric mean, geometric CV%, median, 
minimum, and maximum. This summary may be repeated by 
 
and 
 as 
appropriate.
Serum concentrations above cut-offs (i.e. minimum protective concentration) may be 
considered to have functional inhibition. Functional inhibition data may be summarized as 
appropriate. 
A listing of concentration‑time data including PK scheduled timepoints, actual sample 
collection times, sample actual relative times, as well as derived sampling time deviations 
will be presented using the PK Analysis Set. 
Combined individual serum concentrations versus actual times grouped by mAb component
will be plotted on both linear and semi‑logarithmic scales using the PK Analysis Set. 
Geometric means of concentration data will be plotted over time on both linear and 
CCI
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semi‑logarithmic scales as appropriate. Additional geometric mean plots by age and 
vaccination status may be provided. Nominal sampling time points relative to dosing will 
be used for mean plots. Actual sampling time points relative to dosing will be used for 
individual plots.
4.3.2
PK Parameters 
Pharmacokinetic parameters will be derived using non-compartmental analysis methods, if 
data permit.
4.3.2.1
Derivation of PK Parameters 
Where possible, the following key PK parameters in Table 9 will be estimated for each 
individual mAb (AZD8895,  AZD1061) and AZD7442, if data permit.
Table 9 Key PK Parameters
Cmax
Maximum concentration
AUC(0-180days)
Area under the concentration-curve from time zero to 180 days post-dose
AUClast
Area under the concentration-curve from time zero to the time of last 
quantifiable concentration
AUCinf
Area under the concentration-time curve from time zero extrapolated to 
infinity 
t½λz
Terminal elimination half-life, estimated as (ln2)/ #z
tlast
Time of last quantifiable concentration
CL
Clearance 
Vz
Volume of distribution based on terminal phase 
Vss
Volume of distribution at steady state 
The following PK diagnostic parameters will also be calculated for for individual mAb 
(AZD8895,  AZD1061) and AZD7442, if data permit. 
Table 10 PK Diagnostic Parameters
λz lower
Lower (earlier) t used for λz determination
λz upper
Upper (later) t used for λz determination
λz, N
Number of data points included in the log-linear regression analysis
λz span ratio
Time period over which λz was determined as ratio of t½λz
Rsq_adj
Statistical measure of fit for the regression used for λz determination 
adjusted for the number of used data points (n obs)
λz
Terminal elimination rate constant
AUCextr
Extrapolated area under the curve from tlast to infinity, expressed as 
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PK analysis will, where data allow, be carried out using actual elapsed times determined 
from the PK sampling times and the dosing time recorded in the database. If actual elapsed 
times are missing, nominal times may be used. Nominal sampling times may be used for 
any agreed interim PK parameter calculations if required.
For day 1, concentrations below the lower limit of quantification (BLQ) from the time of 
pre-dose sampling up to the time of the first quantifiable concentration will be set to a value 
of 0. After this point, BLQ concentrations will be set to missing for all concentration 
profiles. If 2 or more consecutive BLQ concentrations are followed by quantifiable 
concentrations in the terminal portion of the concentration curve, the profile will be deemed 
to have terminated and therefore these quantifiable values will be set to missing for the 
calculation of the PK parameters unless there is a scientific rationale not to do so. If an 
entire concentration-time profile is BLQ, the profile is excluded from the PK analysis.
Area under the concentration curve will be calculated using trapezoidal methods when 
concentrations are increasing and logarithmic trapezoidal method when concentrations are 
decreasing.
Three concentrations higher than the lower limit of quantification are required as a 
minimum for the AUC parameter to be summarised, with at least one of these 
concentrations following Cmax.
4.3.2.2
Presentation of PK Parameters 
Where possible, all PK parameters (except tlast) in Table 9 will be summarised for each 
mAb component and AZD7442 based on the PK Analysis Set using the following 
descriptive statistics: n, geometric mean, geometric CV%, arithmetic mean, SD, median, 
minimum, and maximum. For tlast, only n, median, minimum, and maximum will be
presented. This summary may be repeated by 
 and 
 as 
appropriate.
All PK parameters, including PK diagnostic parameters, will be listed if data permit.  
4.4
Immunogenicity 
Blood samples for determination of anti-drug antibodies (ADA) in serum will be assessed 
at day 1 (pre-dose), visit 4, visit 6, visit 7, visit 9 as shown in the SoA (Section 1.3) of CSP.
Baseline is defined as the last available ADA assessment prior to the first study 
intervention. Post-baseline includes all ADA assessments after study intervention during 
the study period. 
CCI
CCI


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ADA results to AZD8895, AZD1061 and AZD7442 will be reported separately using the 
respective ADA Evaluable Analysis Set as defined in Section 3.2. In the evaluation of ADA 
results to AZD7442, if a component mAb (i.e. AZD8895 or AZD1061) is not ADA 
evaluable, all results from the component would be treated as missing.
4.4.1
ADA Definitions
ADA result from each sample will be reported as either positive or negative. If the sample 
is positive, the ADA titer will be reported as well. ADA-positive samples may also be 
further tested for characterization of the ADA response. 
ADA detection at sample level: 
!
For each mAb component AZD1061 and AZD8895, a sample is considered to be ADA 
positive if the titer is greater than or equal to the respective minimum required dilution 
(MRD) of the assay. 
!
For a sample at a particular visit, AZD7442 is positive for that visit if either AZD1061 
and/or AZD8895 is positive.
!
A sample is considered to be ADA negative if the titer is < MRD of the assay. 
ADA status at participant level: 
ADA positive:
!
A participant is considered ADA-positive to a mAb component AZD1061 or AZD8895 
if having a positive ADA result to the respective mAb at any visit, including baseline 
and all post-baseline measurements. 
!
A participant is considered ADA-positive to AZD7442 if having a positive ADA result 
to AZD8895 and/or AZD1061 at any visit, including baseline and all post-baseline 
measurements. 
!
A participant is considered ADA negative to a mAb component AZD1061 or 
AZD8895 if having negative ADA results to the respective mAb at all visits, including 
baseline and all post-baseline measurements.
!
A participant is considered ADA negative to AZD7442 if having negative ADA results 
to both AZD8895 and AZD1061 at all visits, including baseline and all post-baseline 
measurements.
The proportion of ADA-positive participants in a population is known as ADA prevalence.
Treatment-induced ADA positive:
!
For each mAb component AZD1061 and AZD8895, a participant is treatment-induced 
ADA positive if ADA negative at baseline and ADA positive at ≥ 1 post-baseline 
assessments with ADA titer ≥ 2 folds of the respective MRD.


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!
For AZD7442, A participant is treatment-induced ADA positive if either AZD8895 
and/or AZD1061 is treatment-induced ADA positive.
Treatment-boosted ADA positive:
!
For each mAb component AZD1061 and AZD8895, a participant is treatment-boosted 
ADA positive if ADA positive at baseline and the baseline titer is boosted by ≥ 4 folds 
at ≥1 post-baseline timepoint.
!
For AZD7442, a participant is treatment-boosted ADA positive if either AZD8895 
and/or AZD1061 is treatment-boosted ADA positive. 
Treatment-emergent ADA positive:
!
For each mAb component AZD1061 and AZD8895, a participant is treatment-emergent 
ADA positive if the component is either treatment-induced positive or treatment-
boosted positive.
!
For AZD7442, a participant is treatment-emergent ADA positive if either AZD8895 
and/or AZD1061 is treatment-emergent ADA positive.
The proportion of treatment-emergent ADA-positive participants in a population is known 
as ADA incidence.
Non-treatment-emergent ADA positive:
• For each mAb component AZD1061 and AZD8895, a participant is non-treatment-
emergent ADA positive if the participant is ADA-positive for the respective mAb but not 
fulfilling the criteria for being treatment-emergent ADA positive.
• For AZD7442, a participant is non-treatment-emergent ADA positive if at least one 
component is positive, and
─If one component is positive, the positive component is non-treatment-emergent 
ADA positive.
─If both components are positive, both components are non-treatment-emergent ADA 
positive.
Persistently ADA positive:
!
For each mAb component AZD1061 and AZD8895, a participant is persistently ADA 
positive if the participant is treatment-emergent ADA positive, and having at least 2 
ADA post-baseline positive with titer ≥ 2 folds of the respective MRD (with ≥ 16 weeks 


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between first and last positive) or positive with ADA titer ≥ 2 folds of MRD at last post-
baseline assessment. 
!
For AZD7442, a participant is persistently ADA positive if either AZD8895 and/or 
AZD1061 is persistently ADA positive.
Transiently ADA positive:
!
For each mAb component AZD1061 and AZD8895, a participant is transiently ADA 
positive, if the participant is treatment-emergent ADA positive, and having at least one 
post-baseline ADA positive assessment with titer ≥ 2 folds of the respective MRD, and 
not fulfilling the conditions of persistently positive.
!
For AZD7442, a participant is transiently ADA positive if AZD7442 is treatment-
emergent ADA positive and not fulfilling the conditions of persistently positive.
4.4.2
Handling Rule for Negative or Borderline ADA data 
The analysis of serum ADA data will use the following imputation method: ADA titer 
values below the MRD are negative results, hence they are not imputed and are excluded 
from calculation of summary statistics. Titer values of borderline positive ADA samples 
reported as ≤ MRD are imputed as MRD in the calculation of summary statistics on ADA 
titer.
4.4.3
ADA Analysis and Presentation
For AZD1061, AZD8895 and AZD7442, respectively, number and percentage of 
participants in each of the following ADA categories in different treatment groups will be 
summarized descriptively based on the respective ADA Evaluable Analysis Sets: 
!
Participants who are ADA positive at any time during the study, including baseline 
and/or post-baseline.
!
Participants who are ADA positive at baseline only. 
!
Participants who are ADA positive at baseline and at least one post-baseline 
assessment. 
!
Participants who are treatment-emergent ADA positive, reported overall and separately 
as treatment-induced and treatment-boosted participants. 
!
Participants who are non-treatment-emergent ADA positive.
!
Participants who are persistently ADA positive. 
!
Participants who are transiently ADA positive. 
Summary of ADA responses during the study with number and percentage of participants 
in each category will be provided in different treatment groups. Summary statistics of 
maximum ADA titers in each category, displaying min, Q1, median, Q3 and max, will be 
provided by intervention group and study total based on respective ADA evaluable 
analysis set for AZD1061, AZD8895, and AZD7442. 


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For ADA summaries at a single time point (e.g., baseline ADA or by visit) the 
corresponding titer summary of either AZD8895 or AZD1061 will be based on the reported 
titer of the positive sample for that particular visit. For AZD7442, the titer will be the titer 
result of the positive component (i.e. either AZD1061 or AZD8895); if a participant has 
titer results to both AZD1061 and AZD8895, the higher titer result will be used. For 
proportions summarized across visits (e.g., ADA positive at any time) the corresponding 
titer summaries will be based on the maximum titer of all positive samples for each 
participant.
All ADA data will be listed for all participants in the safety analysis set regardless of ADA-
evaluable status.
Individual plots of serum PK concentrations over time by ADA category (i.e. ADA 
negative, treatment-emergent ADA positive, non-treatment-emergent ADA positive) may 
be provided. Additional analysis to evaluate the potential impact of immunogenicity on 
pharmacokinetics and/or safety may be assessed when appropriate.   
4.5
Pharmacodynamics
One of the study exploratory objectives is to evaluate the neutralising responses against 
SARS-CoV-2 in serum. Serum samples will be collected for neutralising responses at time 
points specified in the SoA (Section 1.3) of CSP.
4.5.1
Serum Neutralising Responses Against SARS-CoV-2 
4.5.1.1
Handling Rule for Unquantifiable Neutralizing Titer
The analysis of neutralizing antibody titers and fold rises will use the following imputation 
method: a titer value measured below the LLOQ will be imputed to a value that is half of 
the LLOQ in summaries and analyses but will be listed as reported in the raw data. Titer 
values measured as above the upper limit of quantification (ULOQ) will be imputed at the 
ULOQ value. 
4.5.1.2
Analysis and Presentation 
If data permit, neutralizing antibody titers and fold rises will be summarized by 
interventional group at each scheduled visit based on PD Analysis Set. This analysis may 
be repeated by stratification factors age and vaccination status against COVID-19 at 
screening as appropriate. All neutralizing antibody data will be listed.
Descriptive statistics for neutralizing antibody titers and fold rises may include number of 
participants in the analysis, geometric mean, geometric standard deviation (GSD), 95% CI, 
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The geometric mean titer will be calculated as the anti-logarithm of Σ(log2 transformed 
titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, 
where n is the number of participants with titer information. The GSD for titer values will 
be calculated as the anti-logarithm transformation of the standard deviation of the log 
transformed titer. The 95% CI will be calculated as the anti-logarithm transformation of the 
upper and lower limits for a two-sided CI for the mean of the log-transformed titers.
The titer fold rise is calculated as the ratio of the post-dose titer level to the pre-dose titer 
level. The geometric mean fold rise will be calculated as anti-logarithm of Σ (log2 
transformed (post-dose titer/ pre-dose titer)/n). The GSD and 95% CIs for fold rises will be 
calculated similarly to those for titer values.
Results of the neutralizing response against SARS-CoV-2 may be reported separately from 
the CSR.
4.6
Other Exploratory Analyses
One of study exploratory analyses is to evaluate the efficacy of a single dose of AZD7442 
compared to placebo, administered IV, for the prevention of SARS-CoV-2 infection.  
Exploratory efficacy analyses will be based on Full Analysis Set.
4.6.1
SARS-CoV-2 qRT-PCR Test 
Monitoring of COVID-19 symptoms will be performed as per the schedule of events (refer 
to CSP Section 1.3). A SARS-CoV-2 qRT-PCR test could be performed at the discretion of 
the investigator if the participant met the qualifying symptoms (refer to CSP Table 11).
The incidence ofCOVID-19 will be the proportion of participants with a positive SARS-
CoV-2 qRT-PCR test result occurring after IP dosing. If data permit, the incidence of 
COVID-19 will be summarized by intervention group and study total using appropriate 
descriptive statistics.
Available SARS-CoV-2 qRT-PCR data and participants with qualifying symptoms may be 
listed.
4.6.2
SARS-CoV-2 Serology Test 
Serum samples will be collected (if feasible) as per the schedule of events (refer to CSP 
Section 1.3) for SARS-CoV-2 serology test to monitor participants for infection. To be 
considered positive in the endpoint analysis, the positive result should be tested from a 
validated assay performed at the central laboratory. 


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A participant is considered to have a post-treatment response if serology result is negative 
at baseline and positive at ≥ 1 post-baseline. All available serology data prior to COVID-19 
vaccination (if applicable) during the study will be included in analysis.
If data permit, the proportion of participants with a post-treatment response will be 
summarized by intervention group and study total.
Available serology results may be listed as appropriate.
5
INTERIM ANALYSIS
Please refer to section 3.1 for analyses timing. In general, scope of analyses will be similar 
in all planned analyses or ad-hoc interim analyses (if applicable). If data permit, additional 
analysis may be considered as appropriate. No early stopping decision will be made for 
futility or superiority at the primary or ad-hoc interim analyses (if applicable).
6
REFERENCES
Not applicable
7
APPENDIX
APPENDIX 1. Date Conventions for Prior/Concomitant Medications
START DATE 
STOP DATE 
ACTION
Known
Known or 
ongoing
If medication stop date < enrolment date, assign as 
prior;
If medication start date < enrolment date and 
medication stop date ≥ enrolment date , assign as 
concomitant;
If enrolment date ≤ medication start date, assign as 
concomitant.
Partial
If known components of medication stop date show 
that medication stopped before enrolment date, 
assign as prior;
If medication start date < enrolment date and (known 
components of medication stop date show that 


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medication stopped on or after enrolment date), 
assign as concomitant;
If enrolment date ≤ medication start date, assign as 
concomitant.
Missing, not 
ongoing
If medication stop date is missing, then it can never 
be assigned as prior only;
If medication start date < enrolment date, assign as 
concomitant;
If enrolment date ≤ medication start date, assign as 
concomitant.
Partial
Known or 
ongoing
If medication stop date < enrolment date, assign as 
prior;
If (known components of medication start date show 
that medication started before enrolment date) and 
(medication stop date ≥ enrolment date), assign as 
concomitant;
If known components of medication start date show 
that medication started on or after enrolment date, 
assign as concomitant.
Partial
If known components of medication stop date show 
that medication stopped before enrolment date, 
assign as prior;
If (known components of medication start date show 
that medication started before enrolment date) and 
(known components of medication stop date show 
that medication stopped on or after enrolment date), 
assign as concomitant;
If known components of medication start date show 
that medication started on or after enrolment date, 
assign as concomitant.


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Missing, not 
ongoing
Cannot be assigned as prior only;
If known components of medication start date show 
that medication started before enrolment date, assign 
as concomitant;
If known components of medication start date show 
that medication started on or after enrolment date, 
assign as concomitant.
Missing
Known or 
ongoing
If medication stop date < enrolment date, assign as 
prior;
If medication stop date >= enrolment date, assign as 
concomitant.
Partial
If known components of medication stop date show 
that medication stopped before enrolment date, 
assign as prior;
If known components of medication stop date show 
that medication stopped on or after enrolment date, 
assign as concomitant.
Missing, not 
ongoing
Assign as concomitant