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

• ClinicalTrials.gov Identifier: NCT05011513
• Recruitment Status: Terminated
• First Posted: August 18, 2021
• Results First Posted: August 14, 2023
• Last Update Posted: August 14, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: July 30, 2021
• First Posted Date: August 18, 2021
• Results First Submitted Date: July 20, 2023
• Results First Posted Date: August 14, 2023
• Last Update Posted Date: August 14, 2023
• Actual Study Start Date: August 25, 2021
• Actual Primary Completion Date: July 25, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 20, 2023)

Time to Sustained Alleviation of Overall COVID-19 Signs and Symptoms Through Day 28 [ Time Frame: 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 signs and symptoms. In this outcome measure time to sustained alleviation is reported consolidated for overall COVID-19 signs and symptoms.

Original Primary Outcome Measures (submitted: August 16, 2021)

Time to Sustained Alleviation of All Targeted COVID-19 Signs/Symptoms [ Time Frame: Baseline through Day 28 ]

Analysis set includes COVID-19 symptom onset 1-3 days before treatment.

Current Secondary Outcome Measures (submitted: July 20, 2023)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation [ Time Frame: 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 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.
• Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28 [ Time Frame: 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.
• Percentage of Participants With Death Through Week 24 [ Time Frame: From Day 1 to Week 24 ]
  Percentage of participants with death (all-cause) event were reported in this outcome measure.
• Number of COVID-19 Related Medical Visits Per Day Through Day 28 [ Time Frame: From Day 1 to Day 28 ]
  Number of COVID-19 related medical visits per day were reported in this outcome measure.
• Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28 [ Time Frame: From Day 1 to Day 28 ]
• Percentage of Participants With Severe Signs and Symptoms of COVID-19 Through Day 28 [ Time Frame: 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/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.
• Time to Sustained Resolution of Overall COVID-19 Signs and Symptoms Through Day 28 [ Time Frame: 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.
• Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 [ Time Frame: 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 and symptoms. In this outcome measure time to sustained alleviation is reported for each COVID-19 signs and symptoms.
• Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 [ Time Frame: 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.
• Percentage of Participants With Progression to Worsening Status of COVID-19 Signs and Symptoms [ Time Frame: 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).
• Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5 [ Time Frame: Day 1 and Day 5 ]
  Percentage of participants with a resting peripheral oxygen saturation >=95% were reported in this outcome measure.
• Plasma Concentration Versus Time Summary of PF-07321332 [ Time Frame: 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 [ Time Frame: Baseline, 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.

Original Secondary Outcome Measures (submitted: August 16, 2021)

• Percentage of Participants Who Experience Adverse Events (AEs) [ Time Frame: Baseline through Day 34 ]
• Percentage of Participants Who Experience an AE(s) or Serious Adverse Events (SAEs) that Leads to Study Discontinuation [ Time Frame: Baseline through Day 34 ]
• Proportion of Participants With Severe Signs/Symptoms Attributed to COVID-19 [ Time Frame: Baseline through Day 28 ]
• Time to Sustained Resolution of All Targeted COVID-19 Signs/Symptoms [ Time Frame: Baseline through Day 28 ]
• Duration of Each Targeted COVID-19 Sign/Symptom [ Time Frame: Baseline through Day 28 ]
• Proportion of Participants Progressing to a Worsening Status In 1 or More COVID-19 Signs/Symptoms [ Time Frame: Baseline through Day 28 ]
• Proportion of Participants With a Resting Peripheral Oxygen Saturation ≥95% [ Time Frame: Days 1, 5 ]
• Number of COVID-19 Related Medical Visits [ Time Frame: Baseline through Day 28 ]
• Number of Days in Hospital and Intensive Care Unit (ICU) Stay in Participants With COVID-19 Related Hospitalization [ Time Frame: Baseline through Day 28 ]
• Proportion of Participants With COVID-19 Related Hospitalization or Death From Any Cause [ Time Frame: Baseline through Day 28 ]
• Proportion of Participants With Death (all cause) [ Time Frame: Baseline through Week 24 ]
• Minimal Concentration (Ctrough) of PF-07321332 [ Time Frame: Baseline through Day 5 ]
• Viral Titers Measured Via Reverse Transcription Polymerase Chain Reaction (RT-PCR) in Nasal Swabs [ Time Frame: Baseline through Day 14 ]
• Time to Sustained Alleviation of All Targeted COVID-19 Signs/Symptoms [ Time Frame: Baseline through Day 28 ]
  Analysis set includes COVID-19 symptom onset 1-5 days before treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients (EPIC-SR).
• Official Title: 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
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-blind

Primary Purpose: Treatment

• Condition: COVID-19

Intervention

• Drug: PF-07321332
  PF-07321332 (tablet)
• Drug: Ritonavir
  Ritonavir (capsule)
• Drug: Placebo
  Placebo (tablet)
• Drug: Placebo
  Placebo (capsule)

Study Arms

• Experimental: PF-07321332/ritonavir
  Orally administered PF-07321332+ritonavir
  Interventions:

  • Drug: PF-07321332
  • Drug: Ritonavir
• Placebo Comparator: Placebo
  Orally administered Placebo
  Interventions:

  • Drug: Placebo
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 20, 2023): 1440
• Original Estimated Enrollment (submitted: August 16, 2021): 1140
• Actual Study Completion Date: July 25, 2022
• Actual Primary Completion Date: July 25, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Bulgaria, Colombia, Czechia, Hungary, Japan, Korea, Republic of, Malaysia, Mexico, Poland, Puerto Rico, Romania, Slovakia, South Africa, Spain, Thailand, Turkey, Ukraine, United States
• Removed Location Countries: Russian Federation, Taiwan

Administrative Information

• NCT Number: NCT05011513
• Other Study ID Numbers: C4671002; 2021-002857-28 ( EudraCT Number ); EPIC-SR ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: July 2023