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

Study Overview
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Brief Summary
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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.

Detailed Description
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Throughout the study period, provision will be made to allow study visits to be conducted at a participant's home or at another non-clinic location, if available. The total study duration is up to 24 weeks.

Official Title
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AN INTERVENTIONAL EFFICACY AND SAFETY, PHASE 2/3, DOUBLE-BLIND, 2 ARM STUDY TO INVESTIGATE ORALLY ADMINISTERED PF 07321332/RITONAVIR COMPARED WITH PLACEBO IN NONHOSPITALIZED SYMPTOMATIC ADULT PARTICIPANTS WITH COVID-19 WHO ARE AT LOW RISK OF PROGRESSING TO SEVERE ILLNESS

Conditions
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COVID-19

Intervention / Treatment
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* Drug: PF-07321332
* Drug: Ritonavir
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed SARS-CoV-2 infection 5 days prior to randomization Initial onset of COVID-19 signs/symptoms within 5 days of randomization Fertile participants must agree to use a highly effective method of contraception Exclusion Criteria: Has at least one 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 diagnosis of SARS-CoV-2 infection (reinfection) Known medical history of liver disease Receiving dialysis or have known renal impairment Known Human Immunodeficiency Virus (HIV) infection with viral load > 400 copies/ml or taking prohibited medications for HIV treatment Suspected or confirmed concurrent active systemic infection other than COVID-19 Current or expected use of any medications or substances that are highly dependent on Cytochrome P450 3A4 (CYP3A4) for clearance or are strong inducers of CYP3A4 Has received or is expected to receive monoclonal antibody treatment or convalescent COVID-19 plasma Has received any SARS-CoV-2 vaccine within 12 months of screening Participating in another interventional clinical study with an investigational compound or device, including those for COVID-19 Known prior participation in this trial or other trial involving PF-07321332 Oxygen saturation of < 92% on room air Females who are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible participants with a confirmed diagnosis of SARS-CoV-2 infection will be randomized (1:1) to receive PF-07321332/ritonavir or placebo orally every 12 hours for 5 days (10 doses total).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-07321332/ritonavir<br>Orally administered PF-07321332+ritonavir | Drug: PF-07321332<br>* PF-07321332 (tablet)<br>Drug: Ritonavir<br>* Ritonavir (capsule)<br>|
| Placebo Comparator: Placebo<br>Orally administered Placebo | Drug: Placebo<br>* Placebo (tablet)<br>Drug: Placebo<br>* Placebo (capsule)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Sustained Alleviation of Overall COVID-19 Signs and Symptoms Through 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 signs and symptoms. In this outcome measure time to sustained alleviation is reported consolidated for overall COVID-19 signs and symptoms. | From Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | 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 events that started on or after the study medication start date and time. AEs included both serious and all non-serious adverse events. AEs that led to study discontinuation and AEs that led to discontinuation of study intervention and then continued study were also reported in this outcome measure. | From start of study intervention (Day 1) up to Day 34 | 
| Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through 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. | From Day 1 to Day 28 | 
| Percentage of Participants With Death Through Week 24 | Percentage of participants with death (all-cause) event were reported in this outcome measure. | From Day 1 to Week 24 | 
| Number of COVID-19 Related Medical Visits Per Day Through Day 28 | Number of COVID-19 related medical visits per day were reported in this outcome measure. | From Day 1 to Day 28 | 
| Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28 |  | From Day 1 to Day 28 | 
| Percentage of Participants With Severe Signs and Symptoms of COVID-19 Through 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/taste was the same as usual, 1 if the sense of smell/taste was less than usual, and 2 for no sense of smell/taste. | From Day 1 to Day 28 | 
| Time to Sustained Resolution of Overall COVID-19 Signs and Symptoms Through 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. | From Day 1 to Day 28 | 
| Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through 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 and symptoms. In this outcome measure time to sustained alleviation is reported for each COVID-19 signs and symptoms. | From Day 1 to Day 28 | 
| Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through 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. | From Day 1 to Day 28 | 
| Percentage of Participants With Progression to Worsening Status of COVID-19 Signs and Symptoms | 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). | From Day 1 to Day 28 | 
| Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5 | Percentage of participants with a resting peripheral oxygen saturation >=95% were reported in this outcome measure. | Day 1 and Day 5 | 
| Plasma Concentration Versus Time Summary of PF-07321332 |  | Day 1: 1 hour post dose; Day 5: 0 minutes pre-dose | 
| Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Nasal samples were collected to estimate the viral load in participants in terms of logarithm to base 10 (log10) copies per milliliter. | Baseline, Days 3, 5, 10 and 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2 Infection