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NCT05011513

Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients (EPIC-SR).

Terminated Phase 2, PHASE3 Results posted Last updated 14 August 2023
What this trial tests

Phase 2, PHASE3 trial testing PF-07321332 in COVID-19 in 1,440 participants. Terminated before completion.

Timeline
25 August 2021
Primary endpoint
25 July 2022
25 July 2022

Quick facts

Lead sponsorPfizer
PhasePhase 2, PHASE3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment1,440
Start date25 August 2021
Primary completion25 July 2022
Estimated completion25 July 2022
Sites225 locations across Colombia, Japan, Malaysia, Poland, South Korea, Mexico, Thailand, Bulgaria

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Sustained Alleviation of Overall COVID-19 Signs and Symptoms Through Day 28 Primary · From Day 1 to Day 28

Sustained alleviation of targeted COVID-19 signs/symptoms was defined as the event occurring on the first 4 consecutive days when all symptoms scored as moderate or severe at the time of enrollment were scored as mild or absent and those scored mild or absent at the time of enrollment were scored as absent. Missing severity at baseline was considered as mild. Time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28, was calculated as time (days) from start of study intervention or placebo (Day 1) until sustained alleviation of all targeted COVID-19 associated si

GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg12.00011.000 – 13.000
Placebo13.00012.000 – 14.000
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation Secondary · From start of study intervention (Day 1) up to Day 34

An AE was defined as any untoward medical occurrence in a participant or clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening ; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity ; congenital anomaly/birth defect; or that was considered as an important medical event. TEAEs were defined as ev

TEAEs
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg169
Placebo153
SAEs
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg8
Placebo13
AEs led to discontinuation of study
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg0
Placebo1
AEs led to discontinue study intervention and continued study
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg16
Placebo5
Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28 Secondary · From Day 1 to Day 28

Percentage of participants with COVID-19 related hospitalization or death from any cause during the first 28 days of the study was estimated using the Kaplan-Meier (KM) method.

COVID-19 hospitalization
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg0.765
Placebo1.577
Death
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg0
Placebo0.158
Percentage of Participants With Death Through Week 24 Secondary · From Day 1 to Week 24

Percentage of participants with death (all-cause) event were reported in this outcome measure.

GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg0
Placebo0.2
Number of COVID-19 Related Medical Visits Per Day Through Day 28 Secondary · From Day 1 to Day 28

Number of COVID-19 related medical visits per day were reported in this outcome measure.

GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg0.00100.0005 – 0.0019
Placebo0.00200.0010 – 0.0038
Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28 Secondary · From Day 1 to Day 28
Hospitalization
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg0.049± 0.591
Placebo0.181± 1.787
ICU
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg0.000± 0.000
Placebo0.065± 1.004
Percentage of Participants With Severe Signs and Symptoms of COVID-19 Through Day 28 Secondary · From Day 1 to Day 28

Participants recorded a daily severity rating of their symptom severity over the past 24 hours based on a 4-point scale in which 0 was reported if no symptoms were present; 1 if mild; 2 if moderate; and 3 if severe. A participant with severe score for any targeted symptoms post-baseline was counted as severe. Vomiting and diarrhea each was rated on a 4-point frequency scale where 0 was reported for no occurrence, 1 for 1 to 2 times, 2 for 3 to 4 times, and 3 for 5 or greater. Sense of smell and sense of taste each be rated on a 3-point Likert scale where 0 was reported if the sense of smell/ta

GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg19.136
Placebo21.643
Time to Sustained Resolution of Overall COVID-19 Signs and Symptoms Through Day 28 Secondary · From Day 1 to Day 28

Sustained resolution was defined as when targeted symptoms are scored as absent for 4 consecutive days. The first day of the 4 consecutive-day period was considered the first event date.

GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg15.00014.000 – 16.000
Placebo16.00015.000 – 17.000
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 Secondary · From Day 1 to Day 28

Sustained alleviation of targeted COVID-19 signs/symptoms was defined as the event occurring on the first 4 consecutive days when all symptoms scored as moderate or severe at the time of enrollment were scored as mild or absent and those scored mild or absent at the time of enrollment were scored as absent. Missing severity at baseline was treated as mild. Time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28, was calculated as time (days) from start of study intervention or placebo (Day 1) until sustained alleviation of all targeted COVID-19 associated signs

Muscle or body aches
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg5.0004.000 – 6.000
Placebo5.0004.000 – 6.000
Shortness of breath or difficulty breathing
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg5.0004.000 – 6.000
Placebo6.0005.000 – 7.000
Chills or shivering
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg3.0003.000 – 4.000
Placebo3.0003.000 – 4.000
Cough
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg7.0006.000 – 8.000
Placebo8.0007.000 – 9.000
Diarrhea
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg6.0005.000 – 9.000
Placebo4.0003.000 – 6.000
Feeling hot or feverish
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg3.000NA – NA
Placebo4.0003.000 – 4.000
Headache
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg5.0004.000 – 5.000
Placebo5.0005.000 – 6.000
Nausea
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg4.0003.000 – 5.000
Placebo4.0003.000 – 5.000
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 Secondary · From Day 1 to Day 28

Sustained resolution was defined as when targeted symptoms are scored as absent for 4 consecutive days. The first day of the 4 consecutive-day period was considered the first event date. In this outcome measure time to sustained resolution is reported consolidated for each COVID-19 signs and symptoms.

Muscle or body aches
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg8.0007.000 – 9.000
Placebo9.0007.000 – 10.000
Shortness of breath or difficulty breathing
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg7.0005.000 – 7.000
Placebo8.0007.000 – 11.000
Chills or shivering
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg4.0003.000 – 5.000
Placebo5.0004.000 – 6.000
Cough
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg11.00010.000 – 12.000
Placebo12.00011.000 – 13.000
Diarrhea
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg6.0006.000 – 8.000
Placebo5.0004.000 – 6.000
Feeling hot or feverish
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg4.0003.000 – 5.000
Placebo5.0005.000 – 6.000
Headache
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg7.0007.000 – 9.000
Placebo9.0008.000 – 10.000
Nausea
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg6.0004.000 – 7.000
Placebo5.0004.000 – 7.000
Percentage of Participants With Progression to Worsening Status of COVID-19 Signs and Symptoms Secondary · From Day 1 to Day 28

Participants recorded a daily severity rating of their symptom severity over the past 24 hours based on a 4-point scale in which 0 was reported if no symptoms were present; 1 if mild; 2 if moderate; and 3 if severe. Vomiting and diarrhea was rated on a 4-point frequency scale where 0 is reported for no occurrence, 1 (mild) for 1 to 2 times, 2 (moderate) for 3 to 4 times, and 3 (severe) for 5 or greater. Progression to a worsening status for any targeted symptom was based up on increasing severity (i.e. the first time any targeted symptoms worsened after treatment relative to baseline).

GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg75.463
Placebo78.515
Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5 Secondary · Day 1 and Day 5

Percentage of participants with a resting peripheral oxygen saturation \>=95% were reported in this outcome measure.

Day 1
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg62.500
Placebo67.857
Day 5
GroupValue95% CI
Nirmatrelvir 300 mg + Ritonavir 100 mg94.671
Placebo93.212

Adverse events — posted to ClinicalTrials.gov

Time frame: SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nirmatrelvir 300 mg + Ritonavir 100 mg
Serious: 8/654 (1%)
Deaths: 0/654
Placebo
Serious: 13/634 (2%)
Deaths: 1/634

Serious adverse events (12 terms)

ReactionSystemNirmatrelvir 300 mg + Rito…Placebo
COVID-19 pneumoniaInfections and infestations
PneumoniaInfections and infestations
COVID-19Infections and infestations
Pneumonia aspirationInfections and infestations
SepsisInfections and infestations
Creatinine renal clearance decreasedInvestigations
Hepatic enzyme increasedInvestigations
Electrolyte imbalanceMetabolism and nutrition disorders
Colon cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple sclerosis relapseNervous system disorders
Osmotic demyelination syndromeNervous system disorders
Respiratory distressRespiratory, thoracic and mediastinal disorders
Other adverse events (11 terms — click to expand)

ReactionSystemNirmatrelvir 300 mg + Rito…Placebo
DysgeusiaNervous system disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Activated partial thromboplastin time prolongedInvestigations
VomitingGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Fibrin D dimer increasedInvestigations
HeadacheNervous system disorders
DyspepsiaGastrointestinal disorders
Blood thyroid stimulating hormone increasedInvestigations

Most-reported serious reactions: COVID-19 pneumonia, Pneumonia, COVID-19, Pneumonia aspiration, Sepsis, Creatinine renal clearance decreased, Hepatic enzyme increased, Electrolyte imbalance.

Data from ClinicalTrials.gov NCT05011513 adverse events section.

Sponsor's own description

The primary hypothesis to be tested is whether or not there is a difference in time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28 between PF-07321332/ritonavir and placebo.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.
    Hammond J, Leister-Tebbe H, Gardner A, Abreu P, et al · · 2022 · cited 1822× · PMID 35172054 · DOI 10.1056/nejmoa2118542
  2. Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study.
    Wong CKH, Au ICH, Lau KTK, Lau EHY, et al · · 2022 · cited 235× · PMID 36216007 · DOI 10.1016/s0140-6736(22)01586-0
  3. Nirmatrelvir Plus Ritonavir: First Approval.
    Lamb YN. · · 2022 · cited 218× · PMID 35305258 · DOI 10.1007/s40265-022-01692-5
  4. Real-world effectiveness of early molnupiravir or nirmatrelvir-ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study.
    Wong CKH, Au ICH, Lau KTK, Lau EHY, et al · · 2022 · cited 204× · PMID 36029795 · DOI 10.1016/s1473-3099(22)00507-2
  5. Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332.
    Zhao Y, Fang C, Zhang Q, Zhang R, et al · · 2022 · cited 182× · PMID 34687004 · DOI 10.1007/s13238-021-00883-2
  6. Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay.
    Narayanan A, Narwal M, Majowicz SA, Varricchio C, et al · · 2022 · cited 148× · PMID 35217718 · DOI 10.1038/s42003-022-03090-9
  7. Oral Nirmatrelvir and Ritonavir in Nonhospitalized Vaccinated Patients With Coronavirus Disease 2019.
    Ganatra S, Dani SS, Ahmad J, Kumar A, et al · · 2023 · cited 110× · PMID 35986628 · DOI 10.1093/cid/ciac673
  8. Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19.
    Hammond J, Fountaine RJ, Yunis C, Fleishaker D, et al · · 2024 · cited 100× · PMID 38598573 · DOI 10.1056/nejmoa2309003

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT05011513.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing