Trial Outcomes & Findings for A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir (NCT NCT05567952)

Last Updated: 2024-10-08

Results Overview

Baseline was defined as the latest measurement between Day -1 and Day 1, but post-dose samples that were collected within 1 hour post start of dosing were also treated as baseline. Samples with result "\< lower limit of quantification (LLOQ)" were imputed as 1.7 log10 copies/milliliter (mL), and samples with result "Not Detected" were imputed as 0.0 log10 copies/mL.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

436 participants

Primary outcome timeframe

Baseline, Day 5

Results posted on

2024-10-08

Participant Flow

A total of 436 participants were randomized and treated in this study with a repeat 5-day treatment course of nirmatrelvir/ritonavir or placebo/ritonavir for mild-to moderate coronavirus disease 2019 (COVID-19).

Participant milestones

Participant milestones
Measure	Nirmatrelvir 300 mg + Ritonavir 100 mg Participants received nirmatrelvir 300 milligrams (mg) (participants with estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 30 to less than \[\<\] 60 milliliter per minute \[mL/min\]/1.73 meters squared \[m\^2\] or estimated creatinine clearance \[CrCl\] \>=30 to \<60 mL/min received 150 mg every 12 hours \[q12h\] for 5 days) and ritonavir 100 mg, orally for 5 days q12h from Day 1 to Day 5.	Placebo + Ritonavir 100 mg Participants received placebo matched to nirmatrelvir followed by ritonavir 100 mg orally, for 5 days q12h from Day 1 to Day 5.
Overall Study STARTED	292	144
Overall Study COMPLETED	280	138
Overall Study NOT COMPLETED	12	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Nirmatrelvir 300 mg + Ritonavir 100 mg Participants received nirmatrelvir 300 milligrams (mg) (participants with estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 30 to less than \[\<\] 60 milliliter per minute \[mL/min\]/1.73 meters squared \[m\^2\] or estimated creatinine clearance \[CrCl\] \>=30 to \<60 mL/min received 150 mg every 12 hours \[q12h\] for 5 days) and ritonavir 100 mg, orally for 5 days q12h from Day 1 to Day 5.	Placebo + Ritonavir 100 mg Participants received placebo matched to nirmatrelvir followed by ritonavir 100 mg orally, for 5 days q12h from Day 1 to Day 5.
Overall Study Lost to Follow-up	3	2
Overall Study Withdrawal by Subject	6	3
Overall Study Other	3	1

Baseline Characteristics

A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nirmatrelvir 300 mg + Ritonavir 100 mg n=292 Participants Participants received nirmatrelvir 300 milligrams (mg) (participants with estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 30 to less than \[\<\] 60 milliliter per minute \[mL/min\]/1.73 meters squared \[m\^2\] or estimated creatinine clearance \[CrCl\] \>=30 to \<60 mL/min received 150 mg every 12 hours \[q12h\] for 5 days) and ritonavir 100 mg, orally for 5 days q12h from Day 1 to Day 5.	Placebo + Ritonavir 100 mg n=144 Participants Participants received placebo matched to nirmatrelvir followed by ritonavir 100 mg orally, for 5 days q12h from Day 1 to Day 5.	Total n=436 Participants Total of all reporting groups
Age, Continuous	53.5 Years STANDARD_DEVIATION 16.52 • n=5 Participants	53.5 Years STANDARD_DEVIATION 16.43 • n=7 Participants	53.5 Years STANDARD_DEVIATION 16.47 • n=5 Participants
Age, Customized 12 to less than 18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Customized 18 to 44 years	88 Participants n=5 Participants	40 Participants n=7 Participants	128 Participants n=5 Participants
Age, Customized 45 to 64 years	121 Participants n=5 Participants	64 Participants n=7 Participants	185 Participants n=5 Participants
Age, Customized >= 65 years	82 Participants n=5 Participants	40 Participants n=7 Participants	122 Participants n=5 Participants
Sex: Female, Male Female	167 Participants n=5 Participants	80 Participants n=7 Participants	247 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	64 Participants n=7 Participants	189 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	159 Participants n=5 Participants	72 Participants n=7 Participants	231 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	131 Participants n=5 Participants	72 Participants n=7 Participants	203 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	13 Participants n=5 Participants	2 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) White	264 Participants n=5 Participants	132 Participants n=7 Participants	396 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 5

Population: Modified intent-to-treat (mITT) analysis population included all participants randomly assigned to study intervention who took at least 1 dose of study intervention and who had a positive viral RNA NP swab test result (\>= 2.0 log10 copies per mL) at baseline. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Nirmatrelvir 300 mg + Ritonavir 100 mg n=218 Participants Participants received nirmatrelvir 300 milligrams (mg) (participants with estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 30 to less than \[\<\] 60 milliliter per minute \[mL/min\]/1.73 meters squared \[m\^2\] or estimated creatinine clearance \[CrCl\] \>=30 to \<60 mL/min received 150 mg every 12 hours \[q12h\] for 5 days) and ritonavir 100 mg, orally for 5 days q12h from Day 1 to Day 5.	Placebo + Ritonavir 100 mg n=113 Participants Participants received placebo matched to nirmatrelvir followed by ritonavir 100 mg orally, for 5 days q12h from Day 1 to Day 5.
Change From Baseline to Day 5 in Viral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribonucleic Acid (RNA) Level in Nasopharyngeal (NP) Swabs: mITT Population	-3.871 Log10 copies/mL Standard Error 0.129 • Interval 0.129 to	-3.166 Log10 copies/mL Standard Error 0.171 • Interval 0.171 to

SECONDARY outcome

Timeframe: Day 1 of dosing maximum up to Day 28 or censoring date, whichever occurred first

Population: mITT analysis population included all participants randomly assigned to study intervention who took at least 1 dose of study intervention and who had a positive viral RNA NP swab test result (\>= 2.0 log10 copies per mL) at baseline. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.

The event of 2 consecutive negative RAT results obtained at least 24 (-2) hours apart through Day 28 was defined as achieving 2 consecutive non-missing RATs with negative results through Day 28, where the 2 tests were at least 22 hours and at most 7 days apart. For the event of 2 consecutive negative RAT results obtained at least 24 hours apart through Day 28, the date of the first negative RAT result was considered the first event date. Time to 2 consecutive negative RAT results obtained at least 24 hours apart defined as: for participant achieving event, time to event = (first event date) -(first dose date) + 1. For participant not achieving event (censored), censoring date was at last date of RAT measurement, time = (censoring date) - (first dose date) + 1 or Day 27 whichever occurred first (Day 27 was last possible day to achieve 2 consecutive negative RAT results obtained at least 24 hours apart through Day 28).

Outcome measures

Outcome measures
Measure	Nirmatrelvir 300 mg + Ritonavir 100 mg n=223 Participants Participants received nirmatrelvir 300 milligrams (mg) (participants with estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 30 to less than \[\<\] 60 milliliter per minute \[mL/min\]/1.73 meters squared \[m\^2\] or estimated creatinine clearance \[CrCl\] \>=30 to \<60 mL/min received 150 mg every 12 hours \[q12h\] for 5 days) and ritonavir 100 mg, orally for 5 days q12h from Day 1 to Day 5.	Placebo + Ritonavir 100 mg n=115 Participants Participants received placebo matched to nirmatrelvir followed by ritonavir 100 mg orally, for 5 days q12h from Day 1 to Day 5.
Time to Two Consecutive Negative Rapid Antigen Test (RAT) Results At Least 24 Hours Apart Through Day 28: mITT Population	4.000 Days Interval 4.0 to 5.0	5.000 Days Interval 5.0 to 6.0

SECONDARY outcome

Timeframe: Day 1 of dosing maximum up to Day 28 or censoring date, whichever occurred first

Sustained alleviation of all targeted COVID-19 signs/symptoms was defined as the event occurring on the first of 2 consecutive days when all symptoms scored as moderate or severe at study entry are scored as mild or absent and all symptoms scored mild or absent at study entry are scored as absent. The first day of the 2 consecutive-day period was considered the first event date. The time to sustained symptom alleviation was defined as for a participant with sustained symptom alleviation, time to event was calculated as (First Event Date) - (First Dose Date) +1. For a participant that either completed Day 28 of the study or discontinued from the study before Day 28 without sustained symptom alleviation (censored), censoring date was at the last date on which symptom alleviation was assessed, and time was calculated as (Censoring Date) - (First Dose Date) +1 or Day 27 whichever occurred first.

Outcome measures

Outcome measures
Measure	Nirmatrelvir 300 mg + Ritonavir 100 mg n=186 Participants Participants received nirmatrelvir 300 milligrams (mg) (participants with estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 30 to less than \[\<\] 60 milliliter per minute \[mL/min\]/1.73 meters squared \[m\^2\] or estimated creatinine clearance \[CrCl\] \>=30 to \<60 mL/min received 150 mg every 12 hours \[q12h\] for 5 days) and ritonavir 100 mg, orally for 5 days q12h from Day 1 to Day 5.	Placebo + Ritonavir 100 mg n=99 Participants Participants received placebo matched to nirmatrelvir followed by ritonavir 100 mg orally, for 5 days q12h from Day 1 to Day 5.
Time to Sustained Alleviation of All Targeted Signs and Symptoms Through Day 28: mITT Population	8.000 Days 95% Confidence Interval 7.000 • Interval 7.0 to 10.0	9.000 Days 95% Confidence Interval 8.000 • Interval 8.0 to 11.0

SECONDARY outcome

Timeframe: Day 1 of dosing up to maximum Week 24 follow-up

Population: Safety population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening (risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or nonpathogenic. TEAEs were defined as AE that started on or after study medication on Day 1 up to Week 24 follow-up. AEs included both SAEs and all non-SAEs.

Outcome measures

Outcome measures
Measure	Nirmatrelvir 300 mg + Ritonavir 100 mg n=289 Participants Participants received nirmatrelvir 300 milligrams (mg) (participants with estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 30 to less than \[\<\] 60 milliliter per minute \[mL/min\]/1.73 meters squared \[m\^2\] or estimated creatinine clearance \[CrCl\] \>=30 to \<60 mL/min received 150 mg every 12 hours \[q12h\] for 5 days) and ritonavir 100 mg, orally for 5 days q12h from Day 1 to Day 5.	Placebo + Ritonavir 100 mg n=144 Participants Participants received placebo matched to nirmatrelvir followed by ritonavir 100 mg orally, for 5 days q12h from Day 1 to Day 5.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation From Study AEs	148 Participants	55 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation From Study SAEs	3 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation From Study AEs leading to discontinuation from study	0 Participants	0 Participants

Adverse Events

Nirmatrelvir 300 mg + Ritonavir 100 mg

Serious events: 3 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo + Ritonavir 100 mg

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nirmatrelvir 300 mg + Ritonavir 100 mg n=289 participants at risk Participants received nirmatrelvir 300 milligrams (mg) (participants with estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 30 to less than \[\<\] 60 milliliter per minute \[mL/min\]/1.73 meters squared \[m\^2\] or estimated creatinine clearance \[CrCl\] \>=30 to \<60 mL/min received 150 mg every 12 hours \[q12h\] for 5 days) and ritonavir 100 mg, orally for 5 days q12h from Day 1 to Day 5.	Placebo + Ritonavir 100 mg n=144 participants at risk Participants received placebo matched to nirmatrelvir followed by ritonavir 100 mg orally, for 5 days q12h from Day 1 to Day 5.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.35% 1/289 • Number of events 1 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.	0.00% 0/144 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/289 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.	0.69% 1/144 • Number of events 1 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.35% 1/289 • Number of events 1 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.	0.00% 0/144 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.
Psychiatric disorders Generalised anxiety disorder	0.35% 1/289 • Number of events 1 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.	0.00% 0/144 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.
Psychiatric disorders Major depression	0.35% 1/289 • Number of events 1 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.	0.00% 0/144 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.

Other adverse events

Other adverse events
Measure	Nirmatrelvir 300 mg + Ritonavir 100 mg n=289 participants at risk Participants received nirmatrelvir 300 milligrams (mg) (participants with estimated glomerular filtration rate \[eGFR\] greater than or equal to \[\>=\] 30 to less than \[\<\] 60 milliliter per minute \[mL/min\]/1.73 meters squared \[m\^2\] or estimated creatinine clearance \[CrCl\] \>=30 to \<60 mL/min received 150 mg every 12 hours \[q12h\] for 5 days) and ritonavir 100 mg, orally for 5 days q12h from Day 1 to Day 5.	Placebo + Ritonavir 100 mg n=144 participants at risk Participants received placebo matched to nirmatrelvir followed by ritonavir 100 mg orally, for 5 days q12h from Day 1 to Day 5.
Nervous system disorders Dysgeusia	10.0% 29/289 • Number of events 29 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.	1.4% 2/144 • Number of events 2 • Day 1 of dosing up to maximum Week 24 follow-up An event may be categorized as serious in 1 participant and non-serious in other, or a participant may experience both serious and non-serious event. Safety population: all participants randomly assigned to study intervention, who took at least 1 dose of study intervention.

Additional Information

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Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publication until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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