EPIC-HR: Study of Oral PF-07321332/Ritonavir Compared With Placebo in Nonhospitalized High Risk Adults With COVID-19
- Registration Number
- NCT04960202
- Lead Sponsor
- Pfizer
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2091
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Orally administered placebo PF-07321332/ritonavir PF-07321332 Orally administered PF-07321332+ritonavir PF-07321332/ritonavir Ritonavir Orally administered PF-07321332+ritonavir
- Primary Outcome Measures
Name Time Method Percentage of Participants With Covid-19 Related Hospitalization or Death From Any Cause Through Day 28- Modified Intent-To-Treat (mITT) Population 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. Using KM method, survival probability for each time interval was calculated as the number of participants surviving divided by the number of participants at risk. Participants who had the event, dropped out, or moved out were not counted as "at risk" i.e., participants who were lost were considered "censored" and were not counted in the denominator.
- Secondary Outcome Measures
Name Time Method Time to Sustained Alleviation of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT1 Population From Day 1 (baseline) to Day 28 Sustained alleviation of all 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. The first day of the 4 consecutive-day period was considered date of first event. Time to sustained alleviation (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained alleviation (censored), time was calculated as censoring date (last date on which symptom alleviation was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Number of Participants With AEs Leading to Discontinuation and Serious Adverse Events (SAEs) From start of study intervention (Day 1) up to end of safety follow-up (Day 34) An AE was any untoward medical occurrence in a participant, temporarily associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect; a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical events.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) From start of study intervention (Day 1) up to end of safety follow-up (Day 34) An adverse event (AE) was any untoward medical occurrence in a participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. Serious adverse event (SAE) was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect; a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical events. AEs included both SAEs and all non-SAEs. An AE was considered as TEAE if the event started on or after start date of study intervention.
Percentage of Participants With Severe Covid-19 Signs and Symptoms Through Day 28- mITT Population From Day 1 to Day 28 Participants were required to record the severity of their Covid-19 symptoms over the past 24 hours daily on a 4-point scale ranging from 0 to 3, higher scores indicated more severity. The scale was reported as 0= no symptoms, 1=mild, 2=moderate and 3=severe. A participant with severe score for any targeted symptoms post-baseline was counted as severe. Percentage of participants with severe Covid-19 signs and symptoms were reported.
Percentage of Participants With Severe Covid-19 Signs and Symptoms Through Day 28- mITT1 Population From Day 1 to Day 28 Participants were required to record the severity of their Covid-19 symptoms over the past 24 hours daily on a 4-point scale ranging from 0 to 3, higher scores indicated more severity. The scale was reported as 0= no symptoms, 1=mild, 2=moderate and 3=severe. A participant with severe score for any targeted symptoms post-baseline was counted as severe. Percentage of participants with severe Covid-19 signs and symptoms were reported.
Percentage of Participants With Severe Covid-19 Signs and Symptoms Through Day 28- mITT2 Population From Day 1 to Day 28 Participants were required to record the severity of their Covid-19 symptoms over the past 24 hours daily on a 4-point scale ranging from 0 to 3, higher scores indicated more severity. The scale was reported as 0= no symptoms, 1=mild, 2=moderate and 3=severe. A participant with severe score for any targeted symptoms post-baseline was counted as severe. Percentage of participants with severe Covid-19 signs and symptoms were reported.
Time to Sustained Resolution of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT1 Population From Day 1 (baseline) to Day 28 Sustained resolution was defined as when all targeted symptoms were scored as absent for 4 consecutive days. Time to sustained resolution (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained resolution (censored), time was calculated as censoring date (last date on which symptom resolution was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Time to Sustained Alleviation of Each Targeted COVID-19 Signs and Symptoms- mITT2 Population From Day 1 (baseline) to Day 28 Sustained alleviation of each targeted COVID-19 signs/symptoms was defined as the event occurring on the first 4 consecutive days when each symptom 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. The first day of the 4 consecutive-day period was considered date of first event. Time to sustained alleviation (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained alleviation (censored), time was calculated as censoring date (last date on which symptom alleviation was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Time to Sustained Resolution of Each Targeted COVID-19 Signs and Symptoms- mITT Population From Day 1 (baseline) to Day 28 Sustained resolution was defined as when each targeted symptom was scored as absent for 4 consecutive days. Time to sustained resolution (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained resolution (censored), time was calculated as censoring date (last date on which symptom resolution was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Plasma Concentration Versus Time Summary of PF-07321332 1 Hour post-dose on Day 1 and pre-dose on Day 5 Percentage of Participants With Covid-19 Related Hospitalization or Death From Any Cause Through Day 28- Modified Intent-To-Treat 1 (mITT1) Population 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 method.
Time to Sustained Alleviation of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT Population From Day 1 (baseline) to Day 28 Sustained alleviation of all 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. The first day of the 4 consecutive-day period was considered date of first event. Time to sustained alleviation (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained alleviation (censored), time was calculated as censoring date (last date on which symptom alleviation was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Time to Sustained Alleviation of Each Targeted COVID-19 Signs and Symptoms- mITT Population From Day 1 (baseline) to Day 28 Sustained alleviation of each targeted COVID-19 signs/symptoms was defined as the event occurring on the first 4 consecutive days when each symptom 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. The first day of the 4 consecutive-day period was considered date of first event. Time to sustained alleviation (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained alleviation (censored), time was calculated as censoring date (last date on which symptom alleviation was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Percentage of Participants Who Died Through Week 24- mITT Population From Day 1 up to Week 24 In this outcome measure, percentage of participants with death due to any cause was presented.
Percentage of Participants Who Died Through Week 24- mITT2 Population From Day 1 up to Week 24 In this outcome measure, percentage of participants with death due to any cause was presented.
Number of COVID-19 Related Medical Visits- mITT1 Population From Day 1 up to Day 34 Medical visits included emergency room, practitioner's office, home healthcare services, urgent care, telephone consultation, outpatient infusion center, other, COVID-19-related-hospitalization (ICU and non-ICU stays). In this outcome measure, COVID-19-related medical visits of participants were reported.
Time to Sustained Resolution of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT2 Population From Day 1 (baseline) to Day 28 Sustained resolution was defined as when all targeted symptoms were scored as absent for 4 consecutive days. Time to sustained resolution (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained resolution (censored), time was calculated as censoring date (last date on which symptom resolution was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Time to Sustained Resolution of Each Targeted COVID-19 Signs and Symptoms- mITT2 Population From Day 1 (baseline) to Day 28 Sustained resolution was defined as when each targeted symptom was scored as absent for 4 consecutive days. Time to sustained resolution (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained resolution (censored), time was calculated as censoring date (last date on which symptom resolution was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Number of Participants With Progression to a Worsening Status in 1 or More Self-reported COVID-19 Associated Symptoms Through Day 28-mITT Population From Day 1 (baseline) to Day 28 Participants were required to record the severity of their Covid-19 symptoms over the past 24 hours daily on a 4-point scale where 0 = no symptoms; 1= mild; 2= moderate; and 3= severe. Vomiting and diarrhea were each rated on a 4-point frequency scale where 0= 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).
Number of Participants With Progression to a Worsening Status in 1 or More Self-reported COVID-19 Associated Symptoms Through Day 28-mITT1 Population From Day 1 (baseline) to Day 28 Participants were required to record the severity of their Covid-19 symptoms over the past 24 hours daily on a 4-point scale where 0 = no symptoms; 1= mild; 2= moderate; and 3= severe. Vomiting and diarrhea were each rated on a 4-point frequency scale where 0= 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).
Percentage of Participants With a Resting Peripheral Oxygen Saturation >=95% at Days 1 and 5- mITT1 Population Day 1, 5 In this outcome measure, the percentage of participants with a resting peripheral oxygen saturation \>=95% were reported.
Percentage of Participants With a Resting Peripheral Oxygen Saturation >=95% at Days 1 and 5- mITT2 Population Day 1, 5 In this outcome measure, the percentage of participants with a resting peripheral oxygen saturation \>=95% were reported.
Change From Baseline in Log10 Transformed Viral Load at Day 3, 5, 10 and 14- mITT1 Population Baseline, Day 3, 5, 10 and 14 The viral load was measured in nasal or nasopharyngeal samples using RT-PCR.
Number of Days in Hospital and ICU for the Treatment of COVID-19- mITT1 Population From Day 1 up to Day 34 Time to Sustained Alleviation of All Targeted COVID-19 Signs and Symptoms Through Day 28- Modified Intent-to-Treat 2 (mITT2) Population From Day 1 (baseline) to Day 28 Sustained alleviation of all 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. The first day of the 4 consecutive-day period was considered date of first event. Time to sustained alleviation (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained alleviation (censored), time was calculated as censoring date (last date on which symptom alleviation was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Time to Sustained Resolution of All Targeted COVID-19 Signs and Symptoms Through Day 28- mITT Population From Day 1 (baseline) to Day 28 Sustained resolution was defined as when all targeted symptoms were scored as absent for 4 consecutive days. Time to sustained resolution (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained resolution (censored), time was calculated as censoring date (last date on which symptom resolution was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Percentage of Participants Who Died Through Week 24- mITT1 Population From Day 1 up to Week 24 In this outcome measure, percentage of participants with death due to any cause was presented.
Change From Baseline in Log10 Transformed Viral Load at Day 3, 5, 10 and 14- mITT2 Population Baseline, Day 3, 5, 10 and 14 The viral load was measured in nasal or nasopharyngeal samples using RT-PCR.
Number of Days in Hospital and ICU for the Treatment of COVID-19- mITT Population From Day 1 up to Day 34 Time to Sustained Alleviation of Each Targeted COVID-19 Signs and Symptoms- mITT1 Population From Day 1 (baseline) to Day 28 Sustained alleviation of each targeted COVID-19 signs/symptoms was defined as the event occurring on the first 4 consecutive days when each symptom 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. The first day of the 4 consecutive-day period was considered date of first event. Time to sustained alleviation (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained alleviation (censored), time was calculated as censoring date (last date on which symptom alleviation was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Time to Sustained Resolution of Each Targeted COVID-19 Signs and Symptoms- mITT1 Population From Day 1 (baseline) to Day 28 Sustained resolution was defined as when each targeted symptom was scored as absent for 4 consecutive days. Time to sustained resolution (event) was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained resolution (censored), time was calculated as censoring date (last date on which symptom resolution was assessed) minus first dose date plus 1 or Day 25 whichever occurred first.
Number of Participants With Progression to a Worsening Status in 1 or More Self-reported COVID-19 Associated Symptoms Through Day 28-mITT2 Population From Day 1 (baseline) to Day 28 Participants were required to record the severity of their Covid-19 symptoms over the past 24 hours daily on a 4-point scale where 0 = no symptoms; 1= mild; 2= moderate; and 3= severe. Vomiting and diarrhea were each rated on a 4-point frequency scale where 0= 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).
Percentage of Participants With a Resting Peripheral Oxygen Saturation >=95% at Days 1 and 5- mITT Population Day 1, 5 In this outcome measure, the percentage of participants with a resting peripheral oxygen saturation \>=95% were reported.
Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Day 3, 5, 10 and 14- mITT Population Baseline, Day 3, 5, 10 and 14 The viral load was measured in nasal or nasopharyngeal samples using reverse transcription polymerase chain reaction (RT-PCR).
Number of COVID-19 Related Medical Visits- mITT Population From Day 1 up to Day 34 Medical visits included emergency room, practitioner's office, home healthcare services, urgent care, telephone consultation, outpatient infusion center, other, COVID-19-related-hospitalization (intensive care unit \[ICU\] and non-ICU stays). In this outcome measure, COVID-19-related medical visits of participants were reported.
Number of COVID-19 Related Medical Visits- mITT2 Population From Day 1 up to Day 34 Medical visits included emergency room, practitioner's office, home healthcare services, urgent care, telephone consultation, outpatient infusion center, other, COVID-19-related-hospitalization (ICU and non-ICU stays). In this outcome measure, COVID-19-related medical visits of participants were reported.
Number of Days in Hospital and ICU for the Treatment of COVID-19- mITT2 Population From Day 1 up to Day 34
Trial Locations
- Locations (199)
Cahaba Research Inc
🇺🇸Pelham, Alabama, United States
The Institute for Liver Health dba Arizona Clinical Trials
🇺🇸Tucson, Arizona, United States
Hope Clinical Research
🇺🇸Canoga Park, California, United States
Ascada Research
🇺🇸Fullerton, California, United States
Atella Clinical Research LLC.
🇺🇸La Palma, California, United States
Ark Clinical Research
🇺🇸Long Beach, California, United States
American Institute of Research
🇺🇸Los Angeles, California, United States
South Bay Clinical Research Institute
🇺🇸Redondo Beach, California, United States
Hope Clinical Research (COVID Satellite Site)
🇺🇸West Hills, California, United States
Future Innovative Treatments, LLC
🇺🇸Colorado Springs, Colorado, United States
Scroll for more (189 remaining)Cahaba Research Inc🇺🇸Pelham, Alabama, United States