Phase 3
Completed N=2,091
EPIC-HR: Study of Oral PF-07321332/Ritonavir Compared With Placebo in Nonhospitalized High Risk Adults With COVID-19
COVID-19
Source: ClinicalTrials.gov NCT04960202 ↗
Enrolled (actual)
2,091
Serious AEs
4.4%
Results posted
Feb 2023
Primary outcomePrimary: Percentage of Participants With Covid-19 Related Hospitalization or Death From Any Cause Through Day 28- Modified Intent-To-Treat (mITT) Population — 0.752; 6.888 Percentage of participants — p=<0.0001
◆ Published Evidence
Highly cited
2,162citations · ~541 / year
Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.
Summary
The purpose of this study is to determine whether PF-07321332/ritonavir is safe and effective for the treatment of adults who are ill with COVID-19 and do not need to be in the hospital, but are at an increased risk of developing severe illness. Throughout the study period, provision will be made to allow study visits to be conducted at a participant's home or another non-clinic location if available. The total study duration is up to 24 weeks.
Linked Publications (4)
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Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.
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Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A Phase 3 Randomized Trial.
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Integrated virologic analysis of resistance to nirmatrelvir/ritonavir in individuals across four phase 2/3 clinical studies for the treatment of COVID-19.
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Patient-Reported Outcomes of Nirmatrelvir Treatment for High-Risk, Nonhospitalized Adults With Symptomatic COVID-19.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Covid-19 Related Hospitalization or Death From Any Cause Through Day 28- Modified Intent-To-Treat (mITT) Population |
0.752; 6.888 | <0.0001 sig |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
228; 256 | — |
| SECONDARY Number of Participants With AEs Leading to Discontinuation and Serious Adverse Events (SAEs) |
0; 13; 18; 71 | — |
| SECONDARY Percentage of Participants With Covid-19 Related Hospitalization or Death From Any Cause Through Day 28- Modified Intent-To-Treat 1 (mITT1) Population |
0.933; 6.571 | <0.0001 sig |
| SECONDARY Time to Sustained Alleviation of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT Population |
12.00; 15.00 | 0.0003 sig |
| SECONDARY Time to Sustained Alleviation of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT1 Population |
13.00; 15.00 | <0.0001 sig |
| SECONDARY Time to Sustained Alleviation of All Targeted COVID-19 Signs and Symptoms Through Day 28- Modified Intent-to-Treat 2 (mITT2) Population |
13.00; 16.00 | <0.0001 sig |
| SECONDARY Percentage of Participants With Severe Covid-19 Signs and Symptoms Through Day 28- mITT Population |
18.168; 20.775 | 0.3473 |
| SECONDARY Percentage of Participants With Severe Covid-19 Signs and Symptoms Through Day 28- mITT1 Population |
19.691; 21.298 | 0.5762 |
| SECONDARY Percentage of Participants With Severe Covid-19 Signs and Symptoms Through Day 28- mITT2 Population |
20.660; 21.810 | 0.7807 |
| SECONDARY Time to Sustained Resolution of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT Population |
16.00; 18.00 | 0.0053 sig |
| SECONDARY Time to Sustained Resolution of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT1 Population |
16.00; 19.00 | 0.0022 sig |
| SECONDARY Time to Sustained Resolution of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT2 Population |
17.00; 19.00 | 0.0021 sig |
| SECONDARY Time to Sustained Alleviation of Each Targeted COVID-19 Signs and Symptoms- mITT Population |
6.000; 7.000; 6.000; 8.000; 3.000; 5.000 | — |
| SECONDARY Time to Sustained Alleviation of Each Targeted COVID-19 Signs and Symptoms- mITT1 Population |
6.000; 7.000; 6.000; 8.000; 3.000; 5.000 | — |
| SECONDARY Time to Sustained Alleviation of Each Targeted COVID-19 Signs and Symptoms- mITT2 Population |
6.000; 8.000; 6.000; 9.000; 3.000; 5.000 | — |
| SECONDARY Time to Sustained Resolution of Each Targeted COVID-19 Signs and Symptoms- mITT Population |
9.000; 12.000; 8.000; 11.000; 5.000; 7.000 | — |
| SECONDARY Time to Sustained Resolution of Each Targeted COVID-19 Signs and Symptoms- mITT1 Population |
9.000; 12.000; 9.000; 12.000; 5.000; 7.000 | — |
| SECONDARY Time to Sustained Resolution of Each Targeted COVID-19 Signs and Symptoms- mITT2 Population |
9.000; 12.000; 9.000; 13.000; 5.000; 7.000 | — |
| SECONDARY Number of Participants With Progression to a Worsening Status in 1 or More Self-reported COVID-19 Associated Symptoms Through Day 28-mITT Population |
507; 483 | 0.5293 |
| SECONDARY Number of Participants With Progression to a Worsening Status in 1 or More Self-reported COVID-19 Associated Symptoms Through Day 28-mITT1 Population |
735; 737 | 0.6379 |
| SECONDARY Number of Participants With Progression to a Worsening Status in 1 or More Self-reported COVID-19 Associated Symptoms Through Day 28-mITT2 Population |
787; 790 | 0.6760 |
| SECONDARY Percentage of Participants With a Resting Peripheral Oxygen Saturation >=95% at Days 1 and 5- mITT Population |
93.443; 91.963; 92.823; 89.076 | 0.1997 |
| SECONDARY Percentage of Participants With a Resting Peripheral Oxygen Saturation >=95% at Days 1 and 5- mITT1 Population |
93.347; 92.214; 91.577; 87.610 | 0.2810 |
| SECONDARY Percentage of Participants With a Resting Peripheral Oxygen Saturation >=95% at Days 1 and 5- mITT2 Population |
93.353; 91.738; 91.538; 87.681 | 0.2226 |
| SECONDARY Percentage of Participants Who Died Through Week 24- mITT Population |
0; 1.7 | — |
| SECONDARY Percentage of Participants Who Died Through Week 24- mITT1 Population |
0; 1.5 | — |
| SECONDARY Percentage of Participants Who Died Through Week 24- mITT2 Population |
0; 1.4 | — |
| SECONDARY Plasma Concentration Versus Time Summary of PF-07321332 |
2201; 3087 | — |
| SECONDARY Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Day 3, 5, 10 and 14- mITT Population |
-1.829; -1.203; -3.244; -2.923; -4.522; -3.964 | — |
| SECONDARY Change From Baseline in Log10 Transformed Viral Load at Day 3, 5, 10 and 14- mITT1 Population |
-1.790; -1.182; -3.064; -2.213; -4.309; -3.772 | — |
| SECONDARY Change From Baseline in Log10 Transformed Viral Load at Day 3, 5, 10 and 14- mITT2 Population |
-1.828; -1.178; -3.097; -2.239; -4.322; -3.777 | — |
| SECONDARY Number of COVID-19 Related Medical Visits- mITT Population |
22; 81 | — |
| SECONDARY Number of COVID-19 Related Medical Visits- mITT1 Population |
40; 128 | — |
| SECONDARY Number of COVID-19 Related Medical Visits- mITT2 Population |
45; 144 | — |
| SECONDARY Number of Days in Hospital and ICU for the Treatment of COVID-19- mITT Population |
0.088; 0.844; 0.000; 0.179; 0.088; 0.666 | — |
| SECONDARY Number of Days in Hospital and ICU for the Treatment of COVID-19- mITT1 Population |
0.087; 0.766; 0.000; 0.128; 0.087; 0.639 | — |
| SECONDARY Number of Days in Hospital and ICU for the Treatment of COVID-19- mITT2 Population |
0.092; 0.729; 0.000; 0.121; 0.092; 0.610 | — |
Eligibility Criteria
Inclusion Criteria
- Confirmed SARS-CoV-2 infection within 5 days prior to randomization
- Initial onset of COVID-19 signs/symptoms within 5 days prior to the day of randomization and at least 1 of the specified COVID-19 signs/symptoms present on the day of randomization
- Fertile participants must agree to use a highly effective method of contraception
- Has at least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19
Exclusion Criteria
- History of or need for hospitalization for the medical treatment of COVID-19
- Prior to current disease episode, any confirmed SARS-CoV-2 infection
- Known medical history of active liver disease
- Receiving dialysis or have known moderate to severe renal impairment
- Known human immunodeficiency virus (HIV) infection with a viral load greater than 400 copies/mL or taking prohibited medications for HIV treatment
- Suspected or confirmed concurrent active systemic infection other than COVID-19
- History of hypersensitivity or other contraindication to any of the components of the study intervention
- Current or expected use of any medications or substances that are highly dependent on CYP3A4 for clearance or are strong inducers of CYP3A4
- Has received or is expected to receive convalescent COVID-19 plasma
- Has received or is expected to receive any dose of a SARS-CoV-2 vaccine before the Day 34 visit
- Participating in another interventional clinical study with an investigational compound or device, including those for COVID-19 through the long-term follow-up visit
- Known prior participation in this trial or other trial involving PF-07321332
- Oxygen saturation of <92% on room air, or on their standard home oxygen supplementation for those who regularly receive chronic supplementary oxygen for an underlying lung condition
- Females who are pregnant or breastfeeding
Data sourced from ClinicalTrials.gov (NCT04960202) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.