Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSISSYNOPSIS
Study Title: A Phase 2/3, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled
Study to Evaluate the Safety And Efficacy of 2 Regimens of Orally AdministeredPF-07321332/Ritonavir in Preventing Symptomatic SARS-CoV-2 Infection in Adult
Household Contacts of an Individual with Symptomatic COVID-19
Study Number: C4671006
Regulatory Agency or Public Disclosure Identifier Number:
EudraCT Number: 2021-002894-24
ClinicalTrials.gov identification (ID): NCT05047601
Study Phase: 2/3
Name of Study Intervention: PF-07321332 (nirmatrelvir)
Name of Sponsor/Company: Pfizer Inc.
Clinical Study Report (CSR) Version and Report Date: Final CSR Last Participant Last
Visit (LPLV) (Amendment to 27 May 2022) Version 2.0; 07 March 2023
Number of Study Center(s) and Investigator(s):A list of study centers and investigators involved in this study is provided inAppendix 16.1.4.1.
Publications:
Not Applicable.
Study Period:
Study Initiation Date (First Participant First Visit): 09 September 2021
Study Completion (LPLV Date): 12 April 2022
This study was neither discontinued nor interrupted.
Rationale:
The purpose of this study is to evaluate the efficacy and safety of nirmatrelvir/ritonavir as
postexposure prophylaxis for adult household contacts of an individual with symptomaticcoronavirus disease 2019 (COVID-19).
PFIZER CONFIDENTIAL
Page 1

Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Objectives, Endpoints, and Statistical Methods:
Table S1. Study Objectives, Endpoints, and Estimands
Type

Objectives

Endpoints

Estimands

Primary:
Efficacy•

Of the participants who have a
To compare thenegative RT-PCR result at
efficacy of 5-day andbaseline:
10-day regimens of• Proportion of participants
nirmatrelvir/ritonavir
who develop a
versus placebo insymptomatic, RT-PCR or
preventing
RAT-confirmed
symptomatic reverse
SARS-CoV-2 infection
transcription
through Day 14.
polymerase chain
reaction (RT-PCR) or
rapid antigen test
(RAT)-confirmed
severe acute respiratory
syndrome coronavirus
2 (SARS-CoV-2)
infection in adultparticipants who have anegative RT-PCR result
at baseline and who arehousehold contacts ofan individual withsymptomatic
COVID-19.

•

The risk reduction between
5-day and 10-day regimens of
nirmatrelvir/ritonavir versus
placebo in the proportion ofindividuals who develop
symptomatic RT-PCR or
RAT-confirmed SARS-CoV-2
infection through Day 14 inadults who have a negative
RT-PCR result at baseline andare household contacts of anindividual with symptomatic
COVID-19. This will be
estimated without regard toadherence to randomized
treatment.

Safety•To describe the safety
and tolerability of
5-day and 10-day
regimens of
nirmatrelvir/ritonavir
relative to placebo in
adult participants who
have a negative or
positive RT-PCR result
at baseline and who arehousehold contacts ofan individual withsymptomatic
COVID-19.

• Incidence of treatment
emergent adverse events(TEAEs)• Incidence of serious adverse
events (SAEs) and adverse
events (AEs) leading todiscontinuation.

•

Not applicable.

Efficacy•

To compare theefficacy of 5-day and
10-day regimens of
nirmatrelvir/ritonavir
versus placebo in
preventing
symptomatic
RT-PCR or
RAT-confirmed
SARS-CoV-2 infection

Of the participants who have anegative RT-PCR result atbaseline and who are atincreased risk of severe
COVID-19 illness:• Proportion of participants
with symptomatic,
RT-PCR or
RAT-confirmed SARS-•The risk reduction between
5-day and 10-day regimens of
nirmatrelvir/ritonavir versus
placebo in the proportion ofindividuals who develop
symptomatic RT-PCR or
RAT-confirmed SARS-CoV-2
infection through Day 14 inadults who have a negative
RT-PCR result at baseline,

Secondary:

PFIZER CONFIDENTIAL
Page 2Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives, Endpoints, and Estimands
Type

Objectives

Endpoints

in adult participants
who have a negative
RT-PCR result atbaseline, who are atincreased risk of severe
COVID-19 illness, and
who are household
contacts of anindividual withsymptomatic
COVID-19.

CoV-2 infection throughDay 14.
• Proportion of participants
with COVID-19 related
hospitalization or deathfrom any cause by Day 28.

Estimands
who are at increased risk ofsevere COVID-19 illness, and
who are household contacts ofan individual withsymptomatic COVID-19. This
will be estimated without
regard to adherence torandomized treatment.

Efficacy•

To compare theefficacy of 5-day and
10-day regimens of
nirmatrelvir/ritonavir
versus placebo in
preventing
SARS-CoV-2 infectionin adult participants
who have a negative or
positive RT-PCR result
at baseline and who arehousehold contacts ofan individual withsymptomatic
COVID-19.

Of the participants who have a•negative RT-PCR result atbaseline:• Proportion of participants
with asymptomatic
RT-PCR or
RAT-confirmed
SARS-CoV-2 infection
through Day 14.
• Time to RT-PCR or
RAT-confirmed SARSCoV-2 infection throughDay 14.
Of the participants who have apositive RT-PCR result atbaseline:• Proportion of participants
with symptomatic RT-PCR
or RAT-confirmed
SARS-CoV-2 infection
through Day 14.
Of the participants who have anegative or positive RT-PCR
result at baseline:• Proportion of participants
with symptomatic RT-PCR
or RAT-confirmed
SARS-CoV-2 infection
through Day 14.

Not applicable.

Efficacy•

Of the participants who have a
To compare the•negative RT-PCR result at
efficacy of 5-day andbaseline:
10-day regimens of• Proportion of participants
nirmatrelvir/ritonavirwith no, mild, moderate, orversus placebo in thesevere signs and symptoms
duration and severity of
attributed to COVID-19
COVID-19 related
through Day 28.
signs and symptoms in• Number of days ofadult participants who
symptomatic SARS-CoV-2
have a negative
infection through Day 28.
RT-PCR result atbaseline and who are

Not applicable.

PFIZER CONFIDENTIAL
Page 3Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives, Endpoints, and Estimands
Type

Objectives

Endpoints

Estimands

household contacts ofan individual withsymptomatic
COVID-19.
Pharmacokinetics •To determine thepharmacokinetics (PK)of nirmatrelvir in adultparticipants who have anegative or positive
RT-PCR result atbaseline and who arehousehold contacts ofan individual withsymptomatic
COVID-19.

•

Not applicable.

Efficacy•

To describe all-cause
Of the participants who have a•negative RT-PCR result at
mortality in adultparticipants who have a baseline:
negative RT-PCR result • Proportion of participants
with death (all-cause) throughat baseline and who are
Day 38.
household contacts ofan individual withsymptomatic
COVID-19.

Not applicable.

Efficacy•

To describe the viralload in nasal samples
over time in adultparticipants who have anegative or positive
RT-PCR result atbaseline and who arehousehold contacts ofan individual withsymptomatic
COVID-19.

• Nirmatrelvir PK in plasma
and whole blood (if feasible).

Of the participants who have anegative RT-PCR result atbaseline:• Viral titers measured via
RT-PCR in nasal swabs over
time.

•

Not applicable.

•

Not applicable.

•

Not applicable.

Of the participants who have apositive RT-PCR result atbaseline:• Viral titers measured via
RT-PCR in nasal swabs overtime.

Efficacy•

Of the participants who have a
To describe
hospitalizations in adult negative RT-PCR result atparticipants who have a baseline:
negative RT-PCR result • Number of days of hospitaland intensive care unit (ICU)at baseline and who arestay in participants withhousehold contacts of
COVID-19-related
an individual withhospitalization throughsymptomatic
COVID-19.
Day 28.

Efficacy•

To describe COVID-19
related medical visits inadult participants who
have a negative
RT-PCR result at

Of the participants who have anegative RT-PCR result atbaseline:

PFIZER CONFIDENTIAL
Page 4

Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives, Endpoints, and Estimands
Type

Objectives

Endpoints

Estimands

baseline and who arehousehold contacts ofan individual withsymptomatic
COVID-19.

• Number of COVID-19 related
medical visits throughDay 28.

Table S2. Summary of Efficacy Analyses
Endpoint
Proportion of participants who developed asymptomatic, RT-PCR or RAT-confirmed
SARS-CoV-2 infection through Day 14 forparticipants who had a negative RT-PCR result
at baseline.

Analysis TypePrimary Efficacy
analysis

Proportion of participants who developed asymptomatic, RT-PCR or RAT-confirmed
SARS-CoV-2 infection through Day 14 who hada negative RT-PCR result at baseline.

Sensitivity
Per Protocol
analysis for(PP)
primary endpoint

Proportion of participants who developed asymptomatic, RT-PCR or RAT-confirmed
SARS-CoV-2 infection through Day 14 who hada negative RT-PCR result at baseline.

Sensitivity
mITT
analysis for
excludingprimary endpoint Site 1483

GEE/Generalized
linear model

Proportion of participants who developed asymptomatic, RT-PCR or RAT-confirmed
SARS-CoV-2 infection through Day 14 who hada negative RT-PCR result at baseline.a

Sensitivity
mITT
analysis forprimary endpoint

GEE/Generalized
linear model

Proportion of participants who developed asymptomatic, RT-PCR or RAT-confirmed
SARS-CoV-2 infection through Day 14 who hada negative RT-PCR result at baseline.b

Sensitivity
mITT
analysis forprimary endpoint

GEE/Generalized
linear model

Proportion of participants who developed asymptomatic, RT-PCR or RAT-confirmed
SARS-CoV-2 infection through Day 14 who hada negative RT-PCR result at baseline.

Sensitivity
mITT
analysis forregardless ofprimary endpoint data
cleaning
level

GEE/Generalized
linear model

PFIZER CONFIDENTIAL
Page 5Population
modified
Intent-toTreat(mITT)

Analysis Model
Generalized
estimating
equation(GEE)/Generalize
d linear model
Descriptive
statistics
GEE/Generalized
linear modelFinal Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Table S2. Summary of Efficacy Analyses
Endpoint
Proportion of participants who developed asymptomatic, RT-PCR or RAT-confirmed
SARS-CoV-2 infection through Day 14 who hada negative RT-PCR result at baseline.

Analysis Type Population
Sensitivity
mITT byanalysis forconsidering
primary endpoint all
randomized
participantsas
independent
participantsSensitivity
mITT
analysis forprimary endpoint

Analysis Model
GEE/Generalized
linear model

Proportion of participants who developed asymptomatic, RT-PCR or RAT-confirmed
SARS-CoV-2 infection through Day 14 who hada negative RT-PCR result at baseline.c

Sensitivity
mITT
analysis forprimary endpoint

GEE/Generalized
linear model

Proportion of participants who developed asymptomatic, RT-PCR or RAT-confirmed
SARS-CoV-2 infection through Day 14 who hada negative RT-PCR result at baseline.d

SubgroupmITT
analyses for the
primary endpoint

GEE/Generalized
linear model

Proportion of participants with symptomatic,
RT-PCR or RAT-confirmed SARS-CoV-2
infection through Day 14 for participants who
had a negative RT-PCR result at baseline andwho were at increased risk of severe COVID-19
illness.

SecondaryanalysismITT2

GEE/Generalized
linear model

Proportion of participants with symptomatic,
RT-PCR or RAT-confirmed SARS-CoV-2
infection through Day 14 for participants who
had a negative RT-PCR result at baseline andwho were at increased risk of severe COVID-19
illness.

Sensitivity
analysis forsecondary
endpoint

GEE/Generalized
linear model

Proportion of participants with COVID-19
related hospitalization or death from any cause
by Day 28 for participants who had a negative
RT-PCR result at baseline and who were atincreased risk of severe COVID-19 illness.

SecondaryanalysismITT2
consideringallrandomized
participantsas
independent
participants
mITT2

Proportion of participants with asymptomatic
RT-PCR or RAT-confirmed SARS-CoV-2
infection through Day 14 for participants who
had a negative RT-PCR result at baseline.

SecondaryanalysismITT

GEE/Generalized
linear model

Proportion of participants who developed asymptomatic, RT-PCR confirmed SARS-CoV-2
infection through Day 14 who had a negative
RT-PCR result at baseline.

PFIZER CONFIDENTIAL
Page 6

GEE/Generalized
linear model

Descriptive
statistics
Logistic
regression model
if applicableFinal Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Table S2. Summary of Efficacy Analyses
Endpoint
Time to RT-PCR or RAT-confirmed SARSCoV-2 infection through Day 14 for participants
who had a negative RT-PCR result at baseline.

PopulationmITT

Analysis Model
Kaplan-Meierplot; Cox
proportional
hazard model as
neededProportion of participants with symptomatic
Secondary
RT-PCR or RAT-confirmed SARS-CoV-2
analysis
infection through Day 14 in participants who had
a positive RT-PCR result at baseline.

mITT1

GEE/Generalized
linear model

Proportion of participants with symptomatic
RT-PCR or RAT-confirmed SARS-CoV-2
infection through Day 14 in participants who had
a positive RT-PCR result at baseline.

Sensitivity
analysis forsecondary
endpoint

GEE/Generalized
linear model

Proportion of participants with symptomatic
RT-PCR or RAT-confirmed SARS-CoV-2
infection through Day 14 in participants who had
a positive RT-PCR result at baseline.

mITT1 byconsideringallrandomized
participantsas
independent
participants
mITT1

Subgroup
analyses on preor postemergence of theomicron variant
for secondary
endpoint
SecondarymITT3
analysis

GEE/Generalized
linear model

Proportion of participants with symptomatic
RT-PCR or RAT-confirmed SARS-CoV-2
infection through Day 14 in participants who hada negative or positive RT-PCR result at baseline.

Sensitivity
analysis forsecondary
endpoint

GEE/Generalized
linear model

Proportion of participants with symptomatic
RT-PCR or RAT-confirmed SARS-CoV-2
infection through Day 14 in participants who hada negative or positive RT-PCR result at baseline.

Subgroup
analyses on preor postemergence of theomicron variant
for secondary
endpoint

Proportion of participants with symptomatic
RT-PCR or RAT-confirmed SARS-CoV-2
infection through Day 14 in participants who hada negative or positive RT-PCR result at baseline.

Analysis Type
SecondaryanalysisPFIZER CONFIDENTIAL
Page 7mITT3 byconsideringallrandomized
participantsas
independent
participants
mITT3

GEE/Generalized
linear model

GEE/Generalized
linear modelFinal Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Table S2. Summary of Efficacy Analyses
Endpoint
Proportion of participants with no, mild,moderate, or severe signs and symptoms
attributed to COVID-19 through Day 28 forparticipants who had a negative RT-PCR result
at baseline.

Analysis Type
Secondaryanalysis

PopulationmITT

Analysis Model
Descriptive
statistics
Logistic
regression model

Number of days of symptomatic SARS-CoV-2
infection through Day 28 for participants who
had a negative RT-PCR result at baseline.

SecondaryanalysismITT

Descriptive
statistics

Proportion of participants with death (all-cause)through Day 38 for participants who had anegative RT-PCR result at baseline.

SecondaryanalysismITT

Viral titers measured via RT-PCR in nasal swabs Secondary
over time for participants who had a negative
analysis
RT-PCR result at baseline.

mITT

Descriptive
statistics
Logistic
regression model
if applicable
Descriptive
statistics

Viral titers measured via RT-PCR in nasal swabs
over time for participants who had a positive
RT-PCR result at baseline.
Number of days of hospital and ICU stay inparticipants with COVID-19 related
hospitalization through Day 28 for participants
who had a negative RT-PCR result at baseline.

SecondaryanalysismITT1

Descriptive
statistics

SecondaryanalysismITT

Descriptive
statistics

Number of COVID-19 related medical visits
through Day 28 for participants who had anegative RT-PCR result at baseline.

SecondaryanalysismITT

Descriptive
statistics andnegative binomialmodela. If a participant received therapeutic monoclonal antibody or other treatment approved under EUA for
SARS CoV-2 and had a positive RT-PCR or RAT through Day 14, the participant was considered to haveachieved the primary endpoint.
b. If a participant had SARS-CoV-2 Symptom on or before Day 14 and all RT-PCR or RAT were missing
on or after the symptom day through Day 14, the participant was considered to have achieved the primary
endpoint.
c. A participant was considered to have achieved the primary endpoint if 1 of the following criteria weremet:
• Reported symptoms consistent with COVID-19 by Day 14 and was missing infection status for≥4 days through Day 14.
• Had a positive RT-PCR or RAT test result by Day 14 and missing ≥4 daily symptom diary
entries through Day 14.
• Lost to follow-up through Day 14.
d. Subgroup analyses included by age group, sex, race, geographic regions, presence of risk factors
associated with severe COVID-19 illness, pre- or post-emergence of the omicron variant, baseline
serology status.

PFIZER CONFIDENTIAL
Page 8Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Methodology:
This Phase 2/3, randomized, double-blind, double-dummy, placebo-controlled study inapproximately 2880 participants who had a negative screening SARS-CoV-2 RAT result and
who were asymptomatic household contacts of individuals who were symptomatic andrecently tested positive for SARS-CoV-2 (index case: defined as patient with symptomatic
COVID-19) compared the efficacy of 2 regimens of nirmatrelvir/ritonavir versus placebo.
Index cases may have been participants in Phase 2/3 safety and efficacy studies ofnirmatrelvir/ritonavir (C4671002 and C4671005), but this was not required. Eligible
participants for this study were randomly assigned (1:1:1) within 96 hours after collection of
the index case’s first positive SARS-CoV-2 test to treatment in 1 of 3 intervention groups.
The total duration of the study was up to 42 days.
Number of Participants (planned and analyzed):
Approximately 2880 participants were to be randomized to study intervention. The numberof participants analyzed per analysis set was: Full Analysis Set, 2957; Safety Analysis Set,
2942; mITT, 2721; mITT1, 116; mITT2, 2017; mITT3, 2858; and PP, 2361.
Based on the exclusion of 2 sites from the reanalysis, the number of participants analyzed per
analysis set was: Full Analysis Set, 2736; Safety Analysis Set, 2721; mITT, 2514; mITT1,
115; mITT2, 1838; mITT3, 2649; and PP, 2167.
Diagnosis and Main Criteria for Inclusion and Exclusion:
Enrolled in this study were participants who had a negative screening SARS-CoV-2 RAT
result and who were asymptomatic household contacts of individuals who were symptomaticand recently tested positive for SARS-CoV-2 (index case: defined as patient withsymptomatic COVID-19).
Study Interventions, Dose, Mode of Administration, and Batch Number(s):Eligible participants for this study were randomly assigned (1:1:1) within 96 hours aftercollection of the index case’s first positive SARS-CoV-2 test to receive:•

Nirmatrelvir/ritonavir every 12 hours (q12h) for 5 days followed by matching placebo
q12h for 5 days; or•Nirmatrelvir/ritonavir q12h for 10 days; or•Matching placebo for nirmatrelvir/ritonavir q12h for 10 days.

PFIZER CONFIDENTIAL
Page 9Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Table S3. Investigational Product Description, Vendor Lot Number, Pfizer Lot
Number, Strength/Potency, and Dosage Form
Investigational Product
Description

PF-07321332 150 mg Tablet(Croscarmellose Sodium)PF-07321332 150 mg Tablet(Croscarmellose Sodium)PF-07321332 150 mg Tablet(Croscarmellose Sodium)PF-07321332 150 mg Tablet(Croscarmellose Sodium)PF-07321332 150 mg Tablet(Croscarmellose Sodium)
Placebo for PF-07321332 Tablet(Pink Oval)
Placebo for PF-07321332 Tablet(Pink Oval)
Placebo for Ritonavir 100 mg Size
AAA Swedish Orange Capsule
Placebo for Ritonavir 100 mg Size
AAA Swedish Orange Capsule
Ritonavir 100 mg Size AAA
Swedish Orange Capsule
Ritonavir 100 mg Size AAA
Swedish Orange Capsule

Vendor Lot
Number

Pfizer Lot
NumberStrength/
Potency

DosageForm

FG913121-DP-00654

150 mgTABLET

FG994621-DP-00680

150 mgTABLET

FJ139921-DP-00677

150 mgTABLET

FK078121-DP-00808

150 mgTABLET

N/A

21-DP-00651

150 mgTABLET

N/A

21-DP-00601

0 mg

TABLET

N/A

21-DP-00720

0 mg

TABLET

74132.3

21-DP-00682

0 mg

CAPSULE

74132.5

21-DP-00704

0 mg

CAPSULE

74132.10

21-DP-00727

100 mgCAPSULE

74132.4

21-DP-00681

100 mgCAPSULE

Duration of Study Intervention:
The planned treatment duration is 10 days or 11 days depending if 2 doses or 1 dose of study
intervention were administered on Day 1, respectively.
Summary of Results:
Demographic and Other Baseline Characteristics:
Baseline characteristics, including risk factors for progression to severe COVID-19 werebalanced across treatment groups:•

The mean (SD) age of participants was 43.06 (14.77) years with similar proportion ofMales (46.8%) and Females (53.2%).

•

At Baseline, most participants (94.7%) had a negative RT-PCR confirmed
SARS-CoV-2 result .

•At Baseline, most participants had a positive serology antibody test (90.7%).
PFIZER CONFIDENTIAL
Page 10

Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS•

Most participants (72.6%) had at least 1 protocol-defined risk factor for progression
to severe COVID-19•

Most participants (87.0%) had not received a COVID-19 vaccine.

•

Most participants (69.5%) were in the United States.

Participants in this study were household contacts of individuals who were symptomatic andhad recently tested positive for SARS-CoV-2 (ie, index cases).
Exposure:
Overall, most participants received study intervention for 10 days (ie, 2 doses of study
intervention were administered on Day 1) or 11 days (ie, 1 dose of study intervention was
administered on Day 1).
Efficacy Results:
Primary Endpoint Results
The study was powered to detect a 70% risk reduction of developing symptomatic, RT-PCR
or RAT confirmed SARS-CoV-2 infection through Day 14 relative to placebo. Among
participants who had a negative RT-PCR result at baseline (ie, mITT), the proportion ofparticipants who developed symptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection
through Day 14 was 2.6% (n=22) for the nirmatrelvir/ritonavir 5-day regimen, 2.4% (n=20)
for the nirmatrelvir/ritonavir 10-day regimen, both lower than the 3.9% (n=33) for placebo.
The risk reduction vs placebo was 29.8% (p=0.1722) and 35.5% (p=0.1163) for the 5-day
and 10-day regimens, respectively.
Primary Endpoint by Subgroup Results
Results of subgroup analyses by participant age, sex, race, geographic region, and pre- or
post-emergence of the omicron variant were generally consistent with the primary analysis
except for presence of risk factors and baseline serology antibody status. In participants withor without risk factors for severe COVID-19 illness, a numerically greater risk reduction ofdeveloping symptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection through Day 14
was observed for nirmatrelvir/ritonavir 5-day (64%) and 10-day (65%) regimens vs placebo
for participants who did not have risk factors for severe COVID-19 than for participants who
had risk factors. In participants with or without antibodies to SARS-CoV-2 at baseline, anumerically greater risk reduction of developing symptomatic RT-PCR or RAT confirmed
SARS-CoV-2 infection through Day 14 was observed in participants for the 5-day (41%) and
10-day (43%) regimens vs placebo who were sero-positive at baseline than in participants
who were sero-negative at baseline.
Key Secondary Endpoint Results
PFIZER CONFIDENTIAL
Page 11

Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Among participants who had a negative RT-PCR result at baseline and were at increased riskof severe COVID-19 illness (ie, mITT2), the proportion of participants with symptomatic
SARS-CoV-2 infection through Day 14 was 2.9% (n=18) and 2.6% (n=16) for thenirmatrelvir/ritonavir 5-day and 10-day regimens, respectively, and 3.5% (n=21) in placebo.
The risk reduction vs placebo was 12.0% (p=0.6766) and 19.1% (p=0.5070) for the 5-day
and 10-day regimens, respectively.
Secondary Endpoint Results
The following efficacy results were reported for participants who had a negative RT-PCR
result at baseline (ie, mITT):•The risk reduction of asymptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection
through Day 14 for the nirmatrelvir/ritonavir 5-day and 10-day regimens vs placebo wassimilar to that observed for the primary endpoint; the risk reduction vs placebo was
32.8% (p=0.1869) and 36.7% (p=0.1221), respectively.

•

RT-PCR or RAT confirmed SARS-CoV-2 infection through Day 14, regardless of thepresence or absence of symptoms, was reported for 39 (4.621%) and 36 (4.337%)
participants in the nirmatrelvir/ritonavir 5-day and 10-day groups, respectively, fewer
than the 58 (6.905%) participants in the placebo group. Statistically significant
differences in the time to RT-PCR or RAT confirmed SARS-CoV-2 infection wereobserved between the 5-day (p=0.0368) and 10-day (p=0.0186) regimens vs placebo.

•

Among participants who had a positive SARS-CoV-2 RT-PCR or RAT result during thestudy, the proportion of participants who reported having no symptoms or having mild,moderate, or severe signs and symptoms consistent with COVID-19 through Day 28 was
generally similar between treatment groups. Among participants who had a negative
SARS-CoV-2 RT-PCR or RAT result, severity of symptoms was generally similar
between treatment groups.

•

The number of days participants had symptomatic RT-PCR or RAT confirmed
SARS-CoV-2 infection through Day 28 varied from 1-2 days to 1-2 weeks or more andno consistent differences between treatment groups were observed.

•

No deaths from any cause occurred through Day 38.

•

No hospitalizations or ICU stays were reported for participants in thenirmatrelvir/ritonavir 5-day or 10-day groups. One participant in the placebo group had
hospitalization ≥1 day.

•A similar proportion of participants across treatment groups reported COVID-19 medical
visits through Day 28: 15.4% participants in the nirmatrelvir/ritonavir 5-day group had
145 medical visits; 12.4% participants in the nirmatrelvir/ritonavir 10-day group had
124 medical visits, and 15.5% participants in the placebo groups had 152 visits.
PFIZER CONFIDENTIAL
Page 12Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Among participants who had a positive RT-PCR result at baseline (ie, mITT1), the risk
reduction of symptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection throughDay 14 was not notably different between the treatment groups: risk reduction vs placebo
was 25.0% (p=0.4126) and -24.4% (p=0.4273) for the nirmatrelvir/ritonavir 5-day and
10-day regimens, respectively. However, analysis of this endpoint was constrained by thesmall sample size of the analysis set (n=115 participants).
Among participants who had a negative, positive, or missing RT-PCR result at baseline (ie,mITT3), there was a trend towards risk reduction of symptomatic RT-PCR or RAT
confirmed SARS-CoV-2 infection through Day 14 for the nirmatrelvir/ritonavir 5-day and
10-day regimens vs placebo: risk reduction was 27.4% (p=0.1333) and 4.7% (p=0.8088),
respectively.
Among participants who had a negative SARS-CoV-2 RT-PCR result at baseline and were atincreased risk of severe COVID-19 illness (ie, mITT2), no COVID-19-related
hospitalizations or deaths from any cause by Day 28 were reported for participants in thenirmatrelvir/ritonavir 5-day or 10-day groups. In the placebo group, there were no deaths and
1 participant had a COVID-19-related hospitalization.
Among participants who had a negative SARS-CoV-2 RT-PCR result at baseline (ie, mITT)
and had viral titers above the limit of detection, mean viral loads were lower for thenirmatrelvir/ritonavir 5-day and 10-day regimens vs placebo and persisted through Day 14,
with the largest differences observed on Day 5, Day 6, and Day 7. Peak mean viral load wasapproximately 0.5 log10 copies/mL lower for the 5-day and 10-day regimens vs placebo.
Among participants who had a positive RT-PCR result at baseline (ie, mITT1), mean viralloads decreased over time for all treatment groups; however, decreases in viral load occurredearlier for the 5-day and 10-day regimens vs placebo, with the largest differences observedon Day 5 and Day 6.
•

Mean viral loads on Day 5 were 1.470 log10 copies/mL (SD=2.057) and 1.413 log10
copies/mL (SD=1.745) for the 5-day and 10-day regimens, respectively, and 2.994 log10
copies/mL (SD=2.677) for placebo.

•

Mean viral loads on Day 6 were 1.065 log10 copies/mL (SD=1.656) and 0.997 log10
copies/mL (SD=1.696) for the 5-day and 10-day regimens, respectively, and 2.466 log10
copies/mL (SD=2.561) for placebo.

Safety Results:
The overall incidence of all-causality TEAEs was generally similar across the treatmentgroups. These AEs were mostly mild (Grade 1) or moderate (Grade 2) in severity, except for
1 severe (Grade 3) event of Dysgeusia and 1 severe (Grade 3) event Fibrin D dimer increasedin the 5-day regimen and 1 severe (Grade 3) event of Dysgeusia in the 10-day regimen. TherePFIZER CONFIDENTIAL
Page 13

Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
were no deaths related to an AE in any treatment group. There were no discontinuations fromthe study due to AEs.
The proportion of participants with all-causality SAEs was low and similar across treatmentgroups. All of the SAEs were severe (Grade 3) except for COVID-19 Pneumonia in the
10-day regimen which was potentially life-threatening (Grade 4). None of these SAEs wereconsidered related to the study intervention.
The proportion of participants in the nirmatrelvir/ritonavir 5-day and 10-day regimens (1.1%
and 1.2%, respectively) and in placebo (1.6%) who discontinued study intervention due to an
AE and continued in the study, was low and generally similar.
Few (≤0.5%) events leading to discontinuation of study intervention in any treatment groupwere considered by the investigator to be related to study intervention.
•

The majority of these AEs that led to discontinuations in nirmatrelvir/ritonavir 5-day
and 10-day regimens were mild (Grade 1) or moderate (Grade 2). There were no
events that were potentially life-threatening (Grade 4).

Overall, the incidence of participants with hemodynamic, inflammatory, or thyroid-related
AESIs was low and comparable between treatment groups.
No clinically meaningful differences were observed between the 5-day and 10-day
nirmatrelvir/ritonavir regimens and placebo with respect to hematology and clinicalchemistry laboratory test results.
No potential Hy’s Law cases were identified in any treatment group for participants withbaseline AST, ALT, and total bilirubin values within the normal range or above the normal
range.
No clinically meaningful findings in vital sign measurements were observed in this study.
The assessments and observations were comparable across treatment groups.
Pharmacokinetic Results:
Geometric mean (Coefficient of Variation [CV]%) concentrations, representative of
maximum observed concentration (Cmax), on Day 1 (30 to 90 minutes postdose) and Day 5(preferably up to 2 hours predose) were 1332 (100%) ng/mL and 1808 (124%) ng/mL,
respectively, for the nirmatrelvir/ritonavir 5-day group; and 1363 (101%) ng/mL and1761 (125%) ng/mL, respectively, for the nirmatrelvir/ritonavir 10-day group.
Conclusions:•

Treatment with the 5-day and 10-day regimens of nirmatrelvir/ritonavir vs placebo
showed a risk reduction of 29.8% (p=0.1722) and 35.5% (p=0.1163), respectively, fordeveloping symptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection through
PFIZER CONFIDENTIAL
Page 14Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS
Day 14 in participants who had a negative RT-PCR result at baseline and were household
contacts of an individual with symptomatic COVID-19. The proportion of participants
who had events was 2.6% (n=22) and 2.4% (n=20) for the 5-day and 10-day regimens,
respectively, and 3.9% (n=33) for placebo.
•

Similar trends towards risk reduction with the 5-day and 10-day regimens vs placebo
were observed regardless of age, sex, race, geographic region, and pre/post emergenceof the omicron variant. A numerically greater risk reduction was observed in the 5-day
and 10-day regimens in participants without risk factors for severe COVID-19 illness
and in participants who were sero-positive at baseline.

•

Treatment with the 5-day and 10-day regimens of nirmatrelvir/ritonavir vs placebo
showed a risk reduction of 32.8% and 36.7%, respectively, for asymptomatic infection
through Day 14 in participants who had a negative RT-PCR result at baseline.

•

In participants who had a positive RT-PCR result at baseline, the antiviral effect of the
5-day and 10-day regimens of nirmatrelvir/ritonavir was demonstrated by a quicker
decrease in mean viral loads compared to placebo, with the largest differences observedon Day 5 and Day 6 where viral load was approximately 1.5 log10 copies/mL lower.
•

In participants who had a negative RT-PCR result at baseline, the antiviral effect of the
5-day and 10-day regimens of nirmatrelvir/ritonavir was demonstrated by astatistically significant difference in the time to RT-PCR or RAT confirmed
SARS-CoV-2 infection relative to placebo, as well as an approximately 0.5 log10
copies/mL reduction in peak viral load level among the subset of participants who had
a viral titer result above the limit of detection.

•

The mean exposures of nirmatrelvir on Day 5 were consistent with the profile predicted
in a preliminary population PK model and were confirmed by exposures (Ctrough)previously associated with nirmatrelvir/ritonavir 300 mg/100 mg.

•

Treatment with the 5-day and 10-day regimens of nirmatrelvir/ritonavir was safe andwell-tolerated.
•

The incidence of all-causality TEAEs was low and generally similar across treatmentgroups. Most all-causality TEAEs in all treatment groups were mild (Grade 1) tomoderate (Grade 2) in severity. No participants in any treatment group experienced
an AE resulting in death.

•

No participants discontinued study due to an AE. The incidence of discontinuation of
study intervention due to an AE was low and generally similar across the treatmentgroups.

•Overall, the incidence of participants with hemodynamic, inflammatory, or
thyroid-related AESIs was low and comparable between treatment groups.
PFIZER CONFIDENTIAL
Page 15

Final Full Clinical Study Report
Protocol C4671006

CLINICAL STUDY REPORT SYNOPSIS•

Treatment with the nirmatrelvir/ritonavir 5-day and 10-day regimens was not
associated with clinically meaningful changes in laboratory values or vital signs.

PFIZER CONFIDENTIAL
Page 16