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    Clinical Trial Results:
    An Interventional Efficacy and Safety, Phase 2, Randomized, Double-Blind, 3-arm Study to Investigate Nirmatrelvir/Ritonavir in Non-Hospitalized Participants at Least 12 Years of age With Symptomatic COVID-19 who are Immunocompromised

    Summary
    EudraCT number
    		 2022-001362-35
    Trial protocol
    		 ES   BG   HU   SK  
    Global end of trial date
    13 Nov 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 May 2024
    First version publication date
    10 May 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    C4671034
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05438602
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer Inc., Pfizer ClinicalTrials.gov Call Center, 001 8007181021, ClinicalTrials.gov_Inquires@pfizer.com
    Scientific contact
    Pfizer Inc., Pfizer ClinicalTrials.gov Call Center, 001 8007181021, ClinicalTrials.gov_Inquires@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Feb 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Nov 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To describe the effect of nirmatrelvir/ritonavir on viral ribonucleic acid (RNA) levels in nasopharyngeal (NP) swabs over time for the treatment of COVID-19 in non-hospitalized symptomatic participants more than or equal to (>=) 12 years of age with COVID-19 who were immunocompromised.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Aug 2022
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Canada: 11
    Country: Number of subjects enrolled
    Brazil: 4
    Country: Number of subjects enrolled
    Spain: 51
    Country: Number of subjects enrolled
    Bulgaria: 1
    Country: Number of subjects enrolled
    Slovakia: 25
    Country: Number of subjects enrolled
    Mexico: 24
    Country: Number of subjects enrolled
    United States: 38
    Worldwide total number of subjects
    157
    EEA total number of subjects
    77
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    1
    Adults (18-64 years)
    107
    From 65 to 84 years
    49
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Main study population (MSP): Participants aged >= 12 years weighing >= 40 kilogram(kg) who were immunocompromised and diagnosed with symptomatic COVID-19 were enrolled. Rebound population (RP): Participants with documented, symptomatic COVID-19 rebound within 14 days after 5-day treatment with nirmatrelvir/ritonavir were enrolled.

    Pre-assignment
    Screening details
    		 MSP: A total of 156 participants were enrolled and 155 participants were treated. RP: A total of 2 participants were enrolled and treated.

    Period 1
    Period 1 title
    Treatment
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Carer, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day
    Arm description
    		 Participants (MSP + RP) received nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) >=30 to less than (<) 60 milliliters per minute (mL/min)/1.73 square meter (m^2) or estimated creatinine clearance (eCrCl) >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nirmatrelvir
    Investigational medicinal product code
    PF-07321332
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received nirmatrelvir 300 mg every 12 hours for 5 days.

    Investigational medicinal product name
    Placebo for Ritonavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received placebo for ritonavir every 12 hours for 10 days.

    Investigational medicinal product name
    Placebo for Nirmatrelvir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received placebo for nirmatrelvir every 12 hours for 10 days.

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ritonavir 100 mg every 12 hours for 5 days.

    Arm title
    		 Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day
    Arm description
    		 Participants (MSP + RP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nirmatrelvir
    Investigational medicinal product code
    PF-07321332
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received nirmatrelvir 300 mg every 12 hours for 10 days.

    Investigational medicinal product name
    Placebo for Nirmatrelvir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received placebo for nirmatrelvir every 12 hours for 5 days.

    Investigational medicinal product name
    Placebo for Ritonavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received placebo for ritonavir every 12 hours for 5 days.

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ritonavir 100 mg every 12 hours for 10 days.

    Arm title
    		 Nirmatrelvir + Ritonavir 15 Day
    Arm description
    		 Participants (MSP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received ritonavir 100 mg every 12 hours for 15 days.

    Investigational medicinal product name
    Nirmatrelvir
    Investigational medicinal product code
    PF-07321332
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received nirmatrelvir 300 mg every 12 hours for 15 days.

    Number of subjects in period 1
    		Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Started
    54
    52
    51
    Completed
    50
    49
    43
    Not completed
    4
    3
    8
         Withdrawal by Participant
    2
    1
    4
         No longer met eligibility criteria
    -
    1
    -
         Adverse event
    2
    1
    3
         Unspecified
    -
    -
    1
    Period 2
    Period 2 title
    Follow-up
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Carer, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nirmatrelvir + Ritonavir 5 day Then Placebo 10 Day
    Arm description
    		 Participants (MSP + RP) received nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) >=30 to less than (<) 60 milliliters per minute (mL/min)/1.73 square meter (m^2) or estimated creatinine clearance (eCrCl) >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Nirmatrelvir + Ritonavir 10-day Then Placebo 5 Day
    Arm description
    		 Participants (MSP + RP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Nirmatrelvir + Ritonavir 15 Day
    Arm description
    		 Participants (MSP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    		Nirmatrelvir + Ritonavir 5 day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10-day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Started
    50
    49
    43
    Completed
    50
    50
    45
    Not completed
    4
    2
    6
         Withdrawal by Participant
    3
    2
    6
         Adverse event
    1
    -
    -
    Joined
    4
    3
    8
         Discontinued treatment but followed up
    4
    3
    8
    Period 3
    Period 3 title
    Long-term follow-up
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Carer, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nirmatrelvir + Ritonavir 5 day Then Placebo 10 Day
    Arm description
    		 Participants (MSP + RP) received nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) >=30 to less than (<) 60 milliliters per minute (mL/min)/1.73 square meter (m^2) or estimated creatinine clearance (eCrCl) >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Nirmatrelvir + Ritonavir 10-day Then Placebo 5 Day
    Arm description
    		 Participants (MSP + RP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Nirmatrelvir + Ritonavir 15 Day
    Arm description
    		 Participants (MSP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 3
    		Nirmatrelvir + Ritonavir 5 day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10-day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Started
    50
    50
    45
    Completed
    47
    47
    44
    Not completed
    7
    5
    7
         Withdrawal by Participant
    4
    5
    6
         Death
    1
    -
    1
         Unspecified
    1
    -
    -
         Lost to follow-up
    1
    -
    -
    Joined
    4
    2
    6
         Also eligible for long term follow-up
    4
    2
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) >=30 to less than (<) 60 milliliters per minute (mL/min)/1.73 square meter (m^2) or estimated creatinine clearance (eCrCl) >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 15 Day
    Reporting group description
    		 Participants (MSP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day Total
    Number of subjects
    		 54 52 51 157
    Age Categorical
    Units: Participants
        Adolescents (12-17 years)
    		 0 1 0 1
        Adults (18-64 years)
    		 34 35 38 107
        From 65-84 years
    		 20 16 13 49
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.09 ( 14.77 ) 54.77 ( 16.20 ) 55.63 ( 14.44 ) -
    Gender Categorical
    Units: Participants
        Female
    		 28 30 26 84
        Male
    		 26 22 25 73
    Race
    Units: Subjects
        White
    		 50 47 44 141
        Black or African American
    		 1 0 1 2
        American Indian or Alaska Native
    		 1 3 3 7
        Not reported
    		 2 1 3 6
        Asian
    		 0 1 0 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 36 33 32 101
        Not Hispanic or Latino
    		 16 19 19 54
        Not Reported
    		 2 0 0 2

    End points

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    End points reporting groups
    Reporting group title
    Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) >=30 to less than (<) 60 milliliters per minute (mL/min)/1.73 square meter (m^2) or estimated creatinine clearance (eCrCl) >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 15 Day
    Reporting group description
    		 Participants (MSP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Reporting group title
    Nirmatrelvir + Ritonavir 5 day Then Placebo 10 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) >=30 to less than (<) 60 milliliters per minute (mL/min)/1.73 square meter (m^2) or estimated creatinine clearance (eCrCl) >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 10-day Then Placebo 5 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 15 Day
    Reporting group description
    		 Participants (MSP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
    Reporting group title
    Nirmatrelvir + Ritonavir 5 day Then Placebo 10 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) >=30 to less than (<) 60 milliliters per minute (mL/min)/1.73 square meter (m^2) or estimated creatinine clearance (eCrCl) >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 10-day Then Placebo 5 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 15 Day
    Reporting group description
    		 Participants (MSP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Primary: Percentage of Participants With Sustained Nasopharyngeal (NP) Swab Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribonucleic Acid (RNA) < Lower Limit of Quantitation (LLOQ) From Day 15 to Day 44: MSP

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    End point title
    		 Percentage of Participants With Sustained Nasopharyngeal (NP) Swab Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribonucleic Acid (RNA) < Lower Limit of Quantitation (LLOQ) From Day 15 to Day 44: MSP [1]
    End point description
    An NP swab was collected by healthcare professional (HCP) from participants and were sent to the central laboratory for viral RNA level testing real-time reverse transcriptase-polymerase chain reaction(RT-PCR). Sustained was defined as NP swab SARS-CoV-2 RNA level not >=2.0 log10 copies/mL at any study visit (through Day 44) following the first study visit where the participant's NP swab SARS-CoV-2 RNA <LLOQ (<2.0 log10 copies/mL). Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Primary
    End point timeframe
    From Day 15 to Day 44
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis was planned for this endpoint.
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Percentage of participants
        number (not applicable)
    61.54
    70.83
    66.00
    No statistical analyses for this end point

    Secondary: Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24: MSP

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    End point title
    		 Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24: MSP
    End point description
    A 6-mL blood sample was collected for adult and paediatric participants and was analysed to measure SARS-CoV-2 RNA by RT-PCR. The LLOQ is <2.0 log10 copies/mL. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 5, 10, 15, 21, 28, 35, and 44; Weeks 12 and 24
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Percentage of participants
    number (not applicable)
        Baseline
    98.08
    97.92
    92.00
        Day 5
    90.38
    93.75
    92.00
        Day 10
    92.31
    95.83
    92.00
        Day 15
    88.46
    91.67
    88.00
        Day 21
    86.54
    93.75
    88.00
        Day 28
    84.62
    95.83
    78.00
        Day 35
    82.69
    93.75
    84.00
        Day 44
    86.54
    91.67
    88.00
        Week 12
    73.08
    87.50
    78.00
        Week 24
    69.23
    85.42
    84.00
    No statistical analyses for this end point

    Secondary: Time to First Sustained NP Swab SARS-CoV-2 RNA < LLOQ for Participants Through Day 44 With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline: MSP

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    End point title
    		 Time to First Sustained NP Swab SARS-CoV-2 RNA < LLOQ for Participants Through Day 44 With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline: MSP
    End point description
    An NP swab was collected by HCP from participants and were sent to the central laboratory for viral RNA level testing RT-PCR. Sustained was defined as NP swab SARS-CoV-2 RNA level not >=2.0 log10 copies/mL at any study visit (through Day 44) following the first study visit where the participant's NP swab SARS-CoV-2 RNA <LLOQ (<2.0 log10 copies/mL). The LLOQ is <2.0 log10 copies/mL. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, ‘Number of Participants Analysed’ signifies with non-missing data in the analysis set.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    46
    44
    45
    Units: Days
        median (confidence interval 95%)
    15.000 (9.000 to 16.000)
    11.000 (10.000 to 15.000)
    10.000 (9.000 to 16.000)
    No statistical analyses for this end point

    Secondary: Time to First NP Swab SARS-Cov-2 RNA <LLOQ for Participants with NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline: MSP

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    End point title
    		 Time to First NP Swab SARS-Cov-2 RNA <LLOQ for Participants with NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline: MSP
    End point description
    An NP swab was collected by HCP from participants and were sent to the central laboratory for viral RNA level testing RT-PCR. The LLOQ is <2.0 log10 copies/mL. Kaplan-Meier method was used for analysis. Time (days) to first NP swab SARS-CoV-2 RNA<LLOQ was calculated as (First Event Date) - (First Dose Date) +1. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, ‘Number of Participants Analysed’ signifies with non-missing data in the analysis set.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    46
    44
    45
    Units: Days
        median (confidence interval 95%)
    9.500 (6.000 to 15.000)
    11.000 (10.000 to 15.000)
    9.000 (6.000 to 11.000)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44: MSP

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    End point title
    		 Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44: MSP
    End point description
    An NP swab was collected by HCP from adult and paediatric participants and were sent to the central laboratory for viral RNA level testing RT-PCR. The LLOQ is <2.0 log10 copies/mL. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 5, 10, 15, 21, 28, 35 and 44
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Percentage of participants
    number (not applicable)
        Baseline
    5.77
    8.33
    4.00
        Day 5
    38.46
    29.17
    38.00
        Day 10
    51.92
    64.58
    58.00
        Day 15
    69.23
    77.08
    72.00
        Day 21
    71.15
    91.67
    78.00
        Day 28
    80.77
    93.75
    76.00
        Day 35
    80.77
    91.67
    84.00
        Day 44
    78.85
    91.67
    88.00
    No statistical analyses for this end point

    Secondary: Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44: MSP

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    End point title
    		 Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44: MSP
    End point description
    An NP swab was collected by HCP from adult and paediatric participants and were sent to the central laboratory for viral RNA level testing RT-PCR. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "n" signifies participants with non-missing data in the analysis set and evaluable at specified time points. Here "Number of Participants Analysed" were participants evaluable for this outcome measure. All participants reported under 'Number of Participants Analysed' contributed data to table but may not have evaluable data for every row.
    End point type
    Secondary
    End point timeframe
    Baseline; Day 5, 10, 15, 21, 28, 35 and 44
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: log10 copies/mL
    arithmetic mean (standard deviation)
        Change at Day 5 (n=45, 43, 45)
    -3.449 ( 1.730 )
    -3.621 ( 1.521 )
    -3.746 ( 1.687 )
        Change at Day 10 (n=45, 43, 45)
    -4.167 ( 2.292 )
    -4.931 ( 1.899 )
    -5.002 ( 1.942 )
        Change at Day 15 (n=44, 42, 42)
    -4.827 ( 2.476 )
    -5.773 ( 1.473 )
    -6.009 ( 2.093 )
        Change at Day 21 (n=42, 42, 40)
    -5.472 ( 2.028 )
    -6.328 ( 1.472 )
    -6.319 ( 1.967 )
        Change at Day 28 (n=43, 42, 38)
    -5.938 ( 2.138 )
    -6.509 ( 1.571 )
    -6.530 ( 1.770 )
        Change at Day 35 (n=40, 41, 42)
    -6.237 ( 1.746 )
    -6.596 ( 1.453 )
    -6.633 ( 1.816 )
        Change at Day 44 (n=42, 42, 42)
    -5.916 ( 1.865 )
    -6.597 ( 1.445 )
    -6.707 ( 1.922 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44

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    End point title
    		 Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44
    End point description
    A 6-mL blood sample was collected for adult and paediatric participants and was analysed to measure SARS-CoV-2 RNA by RT-PCR. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "n" signifies participants with non-missing data in the analysis set and evaluable at specified time points. Here, ‘Number of Participants Analyzed’ signifies participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 5, 10, 15, 21, 28, 35 and 44
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    8
    10
    15
    Units: log10 copies/mL
    arithmetic mean (standard deviation)
        Change at Day 5 (n=7, 10, 15)
    -1.457 ( 0.643 )
    -1.360 ( 0.717 )
    -1.528 ( 0.626 )
        Change at Day 10 (n=8, 9, 14)
    -1.487 ( 0.601 )
    -1.700 ( 0.000 )
    -1.880 ( 0.380 )
        Change at Day 15 (n=8, 9, 14)
    -1.700 ( 0.000 )
    -1.700 ( 0.000 )
    -1.880 ( 0.380 )
        Change at Day 21 (n=7, 10, 14)
    -1.700 ( 0.000 )
    -1.700 ( 0.000 )
    -1.880 ( 0.380 )
        Change at Day 28 (n=7, 10, 12)
    -1.700 ( 0.000 )
    -1.700 ( 0.000 )
    -1.910 ( 0.405 )
        Change at Day 35 (n= 7, 10, 13)
    -1.700 ( 0.000 )
    -1.700 ( 0.000 )
    -1.894 ( 0.392 )
        Change at Day 44 (n= 7, 10, 14)
    -1.700 ( 0.000 )
    -1.700 ( 0.000 )
    -1.880 ( 0.380 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Rebound in SARS-CoV-2 RNA Level in NP Swabs at Follow up: MSP

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    End point title
    		 Number of Participants With Rebound in SARS-CoV-2 RNA Level in NP Swabs at Follow up: MSP
    End point description
    Rebound in SARS-CoV-2 RNA level in NP swabs at follow up (ie, any study visit after end of treatment through Day 44) was defined as a half (0.5) log10 copies/mL increase or greater in SARS-CoV-2 RNA level relative to end of treatment SARS-CoV-2 RNA level based on treatment regimen, with a follow-up viral RNA level >= 2.5 log10 copies/mL. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Day 16 through Day 44
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Participants
    9
    1
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Treatment Discontinuation: MSP

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    End point title
    		 Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Treatment Discontinuation: MSP
    End point description
    An adverse event (AE) was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start emerges. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect. Safety population included all randomised participants who received at least 1 dose of the study intervention.
    End point type
    Secondary
    End point timeframe
    Day 1 of dosing up to Week 24
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    53
    51
    51
    Units: Participants
        TEAEs
    28
    34
    31
        SAEs
    5
    1
    4
        AEs Leading to Study Treatment Discontinuation
    1
    1
    4
    No statistical analyses for this end point

    Secondary: Percentage of Participants With COVID-19-Related Hospitalisation >24 Hours (h) or Death Through Day 28: MSP

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    End point title
    		 Percentage of Participants With COVID-19-Related Hospitalisation >24 Hours (h) or Death Through Day 28: MSP
    End point description
    Hospitalisation >24 h is defined as >24h of acute care in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with severe COVID-19. This included specialised acute medical care unit within an assisted living facility or nursing home. This did not include hospitalisation for the purposes of public health and/or clinical trial execution. Kaplan-Meier method was used for evaluation. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 28
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Percentage of participants
    number (not applicable)
        Hospitalisation
    3.846
    0
    0
        Death
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants With COVID-19-Related Hospitalisation Through Day 44 and Week 24: MSP

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    End point title
    		 Percentage of Participants With COVID-19-Related Hospitalisation Through Day 44 and Week 24: MSP
    End point description
    COVID-19 related hospitalisation is defined as >24h of acute care in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with severe COVID-19. This included specialised acute medical care unit within an assisted living facility or nursing home. This did not include hospitalisation for the purposes of public health and/or clinical trial execution. Kaplan-Meier method was used for evaluation. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44 and Day 1 through Week 24
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Percentage of participants
    number (not applicable)
        Through Day 44
    3.846
    0
    0
        Through Week 24
    3.846
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Death Through Week 24: MSP

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    End point title
    		 Percentage of Participants With Death Through Week 24: MSP
    End point description
    Death due to any cause through week 24 was considered. Kaplan-Meier method was used for evaluation. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Day 1 through Week 24
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Percentage of participants
        number (not applicable)
    1.923
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants With COVID-19-Related Intensive Care Unit (ICU) Admission Through Day 44 and Week 24: MSP

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    End point title
    		 Percentage of Participants With COVID-19-Related Intensive Care Unit (ICU) Admission Through Day 44 and Week 24: MSP
    End point description
    Kaplan-Meier method was used for evaluation. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44 and Day 1 through Week 24
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Percentage of participants
    number (not applicable)
        Through Day 44
    1.923
    0
    0
        Through Week 24
    1.923
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Through Day 44 and Week 24: MSP

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    End point title
    		 Percentage of Participants With Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Through Day 44 and Week 24: MSP
    End point description
    Invasive mechanical ventilation or ECMO were types of oxygen support received in hospital. Kaplan-Meier method was used for evaluation. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44 and Day 1 through Week 24
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Percentage of participants
    number (not applicable)
        Through Day 44
    0
    0
    0
        Through Week 24
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Days in Hospital and ICU Stay Through Day 44 and Through Week 24: MSP

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    End point title
    		 Number of Days in Hospital and ICU Stay Through Day 44 and Through Week 24: MSP
    End point description
    Hospitalization >24 hours is defined as >24h of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe COVID-19. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44 and Day 1 through Week 24
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Days
    arithmetic mean (standard deviation)
        Hospital Stay: Up to Day 44
    0.635 ( 3.453 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        Hospital Stay: Up to Week 24
    0.635 ( 3.453 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        ICU Stay: Up to Day 44
    0.442 ( 3.190 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        ICU Stay: Up to Week 24
    0.442 ( 3.190 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
    No statistical analyses for this end point

    Secondary: Number of COVID-19-Related Medical Visits Through Day 44 and Through Week 24: MSP

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    End point title
    		 Number of COVID-19-Related Medical Visits Through Day 44 and Through Week 24: MSP
    End point description
    Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44 and Day 1 through Week 24
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Medical visits
    arithmetic mean (standard deviation)
        Through Day 44
    0.115 ( 0.615 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        Through Week 24
    0.115 ( 0.615 )
    0.000 ( 0.000 )
    0.020 ( 0.141 )
    No statistical analyses for this end point

    Secondary: Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44: MSP

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    End point title
    		 Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44: MSP
    End point description
    Symptoms alleviation through day44 of each targeted COVID-19 sign/symptom was defined as first time when each targeted symptom scored as moderate/severe at study entry are scored as mild or absent and a targeted symptom scored mild or absent at study entry are scored as absent.COVID-19 targeted signs/symptoms were muscle or body aches,shortness of breath(SOB)or difficulty breathing,chills or shivering, cough,diarrhoea,feeling hot or feverish,headache,nausea,stuffy or runny nose,sense of smell,sense of taste,sore throat,low energy or tiredness, vomit. KM method was used for analysis.Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.Here,“n”signifies number of participants with non-missing data and with baseline severity of mild,moderate and severe of targeted signs/symptoms.Here‘99999’suggests that upper limit/lower limit of CI could not be estimated due to insufficient number of participants with event.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Days
    median (confidence interval 95%)
        Muscle or body aches (n= 36, 39, 41)
    6.000 (4.000 to 9.000)
    9.000 (4.000 to 9.000)
    9.000 (5.000 to 13.000)
        SOB or difficulty breathing(n=26,32,26)
    6.000 (4.000 to 9.000)
    9.000 (4.000 to 9.000)
    6.000 (4.000 to 13.000)
        Chills or shivering (n= 27, 34, 33)
    5.000 (4.000 to 6.000)
    4.000 (4.000 to 5.000)
    5.000 (4.000 to 5.000)
        Cough (n= 50, 44, 44)
    6.000 (5.000 to 9.000)
    9.000 (6.000 to 9.000)
    10.000 (5.000 to 13.000)
        Diarrhea (n= 22, 12, 14)
    9.000 (5.000 to 10.000)
    5.000 (4.000 to 9.000)
    9.000 (4.000 to 22.000)
        Feeling hot or feverish (n= 39, 32, 34)
    5.000 (4.000 to 6.000)
    4.000 (4.000 to 5.000)
    5.000 (4.000 to 5.000)
        Headache (n= 33, 37, 38)
    9.000 (4.000 to 15.000)
    5.000 (4.000 to 9.000)
    5.000 (4.000 to 9.000)
        Nausea (n= 11, 18, 13)
    9.000 (4.000 to 13.000)
    4.000 (4.000 to 5.000)
    6.000 (4.000 to 13.000)
        Stuffy or runny nose (n= 46, 46, 47)
    9.000 (6.000 to 11.000)
    9.000 (5.000 to 9.000)
    9.000 (5.000 to 10.000)
        Sense of smell (n= 15, 21, 20)
    9.000 (6.000 to 10.000)
    9.000 (4.000 to 10.000)
    9.000 (5.000 to 10.000)
        Sense of taste (n= 15, 18, 24)
    10.000 (5.000 to 10.000)
    9.000 (4.000 to 10.000)
    9.000 (6.000 to 13.000)
        Sore throat (n= 33, 38, 37)
    6.000 (4.000 to 6.000)
    5.000 (4.000 to 9.000)
    5.000 (4.000 to 9.000)
        Low energy or tiredness (n= 45, 46, 46)
    9.000 (6.000 to 13.000)
    9.000 (5.000 to 10.000)
    9.000 (5.000 to 14.000)
        Vomit (n= 5, 4, 6)
    6.000 (4.000 to 99999)
    4.000 (-99999 to 99999)
    4.500 (4.000 to 99999)
    No statistical analyses for this end point

    Secondary: Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44: MSP

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    End point title
    		 Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44: MSP
    End point description
    Symptoms resolution through day 44 of each targeted COVID-19 sign/symptom was defined as the first time when each targeted symptom scored as mild, moderate or severe at study entry are scored as absent. COVID -19 targeted signs/symptoms were muscle or body aches, SOB or difficulty breathing, chills or shivering, cough, diarrhoea, feeling hot or feverish, headache, nausea, stuffy or runny nose, sense of smell, sense of taste, sore throat, low energy or tiredness, vomit. KM method was used for analysis. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, “n” signifies number of participants with non-missing data and with baseline severity of mild, moderate and severe of targeted signs and symptoms. Here‘99999’suggests that upper limit of CI could not be estimated due to insufficient number of participants with event.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Days
    median (confidence interval 95%)
        Muscle or body aches (n=36, 39, 41)
    14.500 (10.000 to 19.000)
    11.000 (9.000 to 21.000)
    10.000 (6.000 to 20.000)
        SOB or difficulty breathing (n=26, 32, 26)
    9.000 (5.000 to 13.000)
    9.500 (9.000 to 19.000)
    12.000 (6.000 to 19.000)
        Chills or shivering (n=27, 34, 33)
    6.000 (4.000 to 9.000)
    4.000 (4.000 to 9.000)
    5.000 (4.000 to 6.000)
        Cough (n=50, 44, 44)
    13.000 (10.000 to 20.000)
    12.000 (9.000 to 21.000)
    19.500 (11.000 to 22.000)
        Diarrhea (n= 22, 12, 14)
    9.000 (6.000 to 10.000)
    9.000 (4.000 to 13.000)
    16.500 (4.000 to 26.000)
        Feeling hot or feverish (n= 39, 32, 34)
    9.000 (5.000 to 9.000)
    7.000 (4.000 to 9.000)
    5.000 (4.000 to 6.000)
        Headache (n=33, 37, 38)
    13.000 (9.000 to 15.000)
    10.000 (9.000 to 15.000)
    9.000 (5.000 to 11.000)
        Nausea (n=11, 18, 13)
    9.000 (4.000 to 14.000)
    4.000 (4.000 to 9.000)
    9.000 (4.000 to 13.000)
        Stuffy or runny nose (n= 46, 46, 47)
    14.000 (10.000 to 22.000)
    13.000 (9.000 to 15.000)
    13.000 (9.000 to 16.000)
        Sense of smell (n= 15, 21, 20)
    10.000 (9.000 to 15.000)
    9.000 (5.000 to 11.000)
    9.000 (5.000 to 10.000)
        Sense of taste (n= 15, 18, 24)
    10.000 (9.000 to 14.000)
    10.500 (9.000 to 21.000)
    10.000 (6.000 to 13.000)
        Sore throat (n=33, 38, 37)
    9.000 (5.000 to 11.000)
    9.500 (9.000 to 13.000)
    9.000 (9.000 to 10.000)
        Low energy or tiredness (n= 45, 46, 46)
    27.000 (13.000 to 33.000)
    20.000 (13.000 to 35.000)
    22.000 (15.000 to 99999)
        Vomit (n=5, 4, 6)
    6.000 (4.000 to 99999)
    4.000 (4.000 to 99999)
    4.500 (4.000 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Any Severe Targeted Signs and Symptoms Attributed to COVID-19 Through Day 44: MSP

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    End point title
    		 Percentage of Participants With Any Severe Targeted Signs and Symptoms Attributed to COVID-19 Through Day 44: MSP
    End point description
    COVID -19 targeted signs/symptoms were muscle or body aches, SOB or difficulty breathing, chills or shivering, cough, diarrhoea, feeling hot or feverish, headache, nausea, stuffy or runny nose, sense of smell, sense of taste, sore throat, low energy or tiredness, vomit. Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 44
    End point values
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Nirmatrelvir + Ritonavir 15 Day
    Number of subjects analysed
    52
    48
    50
    Units: Percentage of participants
        number (not applicable)
    28.85
    31.25
    38.00
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 of dosing up to Week 24
    Adverse event reporting additional description
    Safety analysis set included all participants randomly assigned to study intervention.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl>=30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 15 Day
    Reporting group description
    		 Participants (MSP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR >=30 to <60 mL/min/1.73 m^2 or eCrCl >=30 to <60 mL/min received nirmatrelvir 150mg and ritonavir 100mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Reporting group title
    Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day
    Reporting group description
    		 Participants (MSP + RP) received nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR >= 30 to <60 mL/min/1.73 m^2 or eCrCl >= 30 to <60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.

    Serious adverse events
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 15 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 54 (9.26%)
    4 / 51 (7.84%)
    1 / 52 (1.92%)
         number of deaths (all causes)
    1
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Follicular lymphoma
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 51 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 51 (1.96%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 51 (1.96%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 51 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intestinal obstruction
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 51 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pseudomonas infection
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 51 (1.96%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 51 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 51 (1.96%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 51 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fungal infection
         subjects affected / exposed
    0 / 54 (0.00%)
    0 / 51 (0.00%)
    1 / 52 (1.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Nirmatrelvir + Ritonavir 15 Day Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 54 (22.22%)
    19 / 51 (37.25%)
    19 / 52 (36.54%)
    Investigations
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 54 (0.00%)
    3 / 51 (5.88%)
    0 / 52 (0.00%)
         occurrences all number
    0
    3
    0
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    6 / 54 (11.11%)
    14 / 51 (27.45%)
    12 / 52 (23.08%)
         occurrences all number
    6
    14
    12
    Headache
         subjects affected / exposed
    1 / 54 (1.85%)
    1 / 51 (1.96%)
    3 / 52 (5.77%)
         occurrences all number
    1
    1
    4
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 54 (1.85%)
    5 / 51 (9.80%)
    2 / 52 (3.85%)
         occurrences all number
    1
    5
    2
    Diarrhoea
         subjects affected / exposed
    5 / 54 (9.26%)
    4 / 51 (7.84%)
    4 / 52 (7.69%)
         occurrences all number
    5
    5
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Sep 2022
    This protocol was amended based on regulatory feedback to update the primary analysis and include an additional population of nonhospitalized symptomatic participants who are immunocompromised with a rebound in COVID-19.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Primary endpoint data not reported for RP, since there was 1 participant each in 2 arms, it could have led to re-identification of participants. In other sections of results data for RP and MSP have been combined.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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