A Study of a Potential Oral Treatment to Prevent COVID-19 in Adults Who Are Exposed to Household Member(s) With a Confirmed Symptomatic COVID-19 Infection

• ClinicalTrials.gov Identifier: NCT05047601
• Recruitment Status: Completed
• First Posted: September 17, 2021
• Results First Posted: May 6, 2023
• Last Update Posted: May 6, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 1, 2021
• First Posted Date: September 17, 2021
• Results First Submitted Date: April 11, 2023
• Results First Posted Date: May 6, 2023
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: September 9, 2021
• Actual Primary Completion Date: April 12, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 11, 2023)

Percentage of Participants Who Developed Symptomatic RT-PCR or RAT Confirmed SARS-CoV-2 Infection Through Day 14: Among Participants With Negative RT-PCR at Baseline [ Time Frame: From Day 1 to Day 14 ]

Percentage of participants who developed symptomatic Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) or Rapid Antigen Test (RAT) confirmed SARS-Cov-2 infection were reported in this outcome measure. Index case was defined as participants with symptomatic COVID-19.

• Original Primary Outcome Measures (submitted: September 15, 2021): Proportion of participants who have a negative reverse transcription polymerase chain reaction (RT-PCR) result at baseline who develop a symptomatic, RT-PCR confirmed SARS-CoV-2 infection. [ Time Frame: Day 1 through Day 14 ]

Current Secondary Outcome Measures (submitted: April 11, 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 end of safety follow-up (Day 38) ]
  An AE was defined as any untoward medical occurrence in a 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 Who Developed Symptomatic RT-PCR or RAT Confirmed SARS-CoV-2 Infection Through Day 14: Among Participants With Negative RT-PCR at Baseline With Increased Risk of Severe COVID-19 Illness [ Time Frame: From Day 1 to Day 14 ]
  Percentage of participants who had a symptomatic RT-PCR or RAT confirmed SARS-Cov-2 infection were reported in this outcome measure. The risk factors associated with severe covid-19 illness included age greater than or equal to 60 years, body mass index greater than 25, social history of smoking and presence of comorbidities. Index case was defined as participants with symptomatic COVID-19.
• Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28: Among Participants With Negative RT-PCR at Baseline With Increased Risk of Severe COVID-19 Illness [ Time Frame: From Day 1 to Day 28 ]
  The risk factors associated with severe covid-19 illness included age greater than or equal to 60 years, body mass index greater than 25, social history of smoking and presence of comorbidities.
• Percentage of Participants With Asymptomatic RT-PCR or RAT Confirmed SARS-CoV-2 Infection Through Day 14: Among Participants With Negative RT-PCR at Baseline [ Time Frame: From Day 1 to Day 14 ]
  Percentage of participants who had asymptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection through day 14 among participants with negative RT-PCR at baseline were reported in this outcome measure. Index case was defined as participants with symptomatic COVID-19.
• Time to RT-PCR or RAT Confirmed SARS-CoV-2 Infection Through Day 14: Among Participants With Negative RT-PCR at Baseline [ Time Frame: From Day 1 to Day 14 ]
  Number of days between first dose and confirmation of the SARS-CoV-2 infection by RT-PCR or RAT was reported in this outcome measure.
• Percentage of Participants With Symptomatic RT-PCR or RAT Confirmed SARS-CoV-2 Infection Through Day 14: Among Participants With Positive RT-PCR at Baseline [ Time Frame: From Day 1 to Day 14 ]
  Percentage of participants with a positive RT-PCR result at baseline who had a symptomatic SARS-CoV-2 infection confirmed by RAT or RT-PCR through Day 14 were reported in this outcome measure. Index case was defined as participants with symptomatic COVID-19.
• Percentage of Participants With Symptomatic RT-PCR or RAT Confirmed SARS-CoV-2 Infection Through Day 14: Among Participants With Negative, Positive or Missing RT-PCR at Baseline [ Time Frame: From Day 1 to Day 14 ]
  Percentage of participants with a negative, positive, or missing RT-PCR result at baseline, who had a symptomatic SARS-CoV-2 infection confirmed by RAT or RT-PCR through Day 14 were reported in this outcome measure. Index case was defined as participants with symptomatic COVID-19.
• Percentage of Participants With no, Mild, Moderate, or Severe Signs and Symptoms Attributed to COVID-19 Through Day 28: Among Participants With Negative RT-PCR at Baseline [ Time Frame: From Day 1 to Day 28 ]
  Participants were categorized according to severity of signs and symptoms as no, mild, moderate, severe in this outcome measure. The 12 signs and symptoms included stuffy or runny nose, sore throat, shortness of breath or difficulty breathing, cough, low energy or tiredness, muscle or body aches, headache, chills or shivering, feeling hot or feverish, nausea, vomiting, diarrhea. Participants recorded their daily severity rating of their symptoms 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.
• Number of Days of Symptomatic RT-PCR or RAT Confirmed SARS-CoV- 2 Infection Through Day 28: Among Participants With Negative RT-PCR at Baseline [ Time Frame: From Day 1 to Day 28 ]
  This outcome measure has been reported in terms of number of participants according to days of symptomatic SARS-CoV-2 infection through Day 28.
• Plasma Concentration Versus Time Summary of Nirmatrelvir (PF-07321332) [ Time Frame: Day 1: 1 hour post dose; Day 5: 2 hours pre-dose ]
• Percentage of Participants With Death Event Through Day 38: Among Participants With Negative RT-PCR at Baseline [ Time Frame: From Day 1 to Day 38 ]
  Percentage of participants with death (all-cause) event were reported in this outcome measure.
• Viral Load in Nasal Samples Over Time: Among Participants With Negative RT-PCR at Baseline [ Time Frame: From Day 1 to Day 14 ]
  Nasal samples were collected to estimate the viral load in terms of logarithm to base 10 (log10) copies per milliliter in participants with negative RT-PCR at baseline and were reported in this outcome measure.
• Viral Load in Nasal Samples Over Time: Among Participants With Positive RT-PCR at Baseline [ Time Frame: From Day 1 to Day 14 ]
  Nasal samples were collected to estimate the viral load in terms of logarithm to base 10 (log10) copies per milliliter in participants with positive RT-PCR at baseline and were reported in this outcome measure.
• Number of Days of Hospitalization and Intensive Care Unit (ICU) Stay: Among Participants With Negative RT-PCR at Baseline [ Time Frame: From Day 1 to Day 28 ]
  This outcome measure has been presented in terms of participants according to number of days of hospitalization and in ICU as 0 days and more than or equal to 1 day.
• Number of COVID-19 Related Medical Visits Through Day 28: Among Participants With Negative RT-PCR at Baseline [ Time Frame: From Day 1 to Day 28 ]
  In this outcome measure number of COVID-19 related medical visits per day were reported. Number of medical visits per day = number of medical visits/number of days follow up through day 28 visit or the last collection date on or before day 28, if day 28 visit was missing.

Original Secondary Outcome Measures (submitted: September 15, 2021)

• Percentage of participants who experience adverse events [ Time Frame: Day 1 through Day 38 ]
• Efficacy in preventing symptomatic COVID-19 in participants who have a negative RT-PCR result at baseline and are at increased risk of severe COVID-19 illness [ Time Frame: Day 1 through Day 14 ]
  Proportion of participants with symptomatic, RT-PCR confirmed SARS-CoV-2 infection through Day 14
• Efficacy in preventing symptomatic COVID-19 in participants who have a negative RT-PCR result at baseline and are at increased risk of severe COVID-19 illness [ Time Frame: Day 1 through Day 28 ]
  Proportion of participants with COVID-19 related hospitalization or death from any cause
• Prevention of SARS CoV-2 infection in participants by RT-PCR status at enrolment [ Time Frame: Day 1 through Day 14 ]
  Proportion of participants with symptomatic or asymptomatic, RT-PCR confirmed SARS-CoV-2 infection.
• Prevention of SARS CoV-2 infection in participants who have a negative RT-PCR result at baseline [ Time Frame: Day 1 through Day 14 ]
  Time to SARS-CoV-2 infection.
• Compare the duration of COVID-19 related signs and symptoms in participants who have a negative RT-PCR result at baseline [ Time Frame: Day 1 through Day 28 ]
• Compare the severity of COVID-19 related signs and symptoms in participants who have a negative RT-PCR result at baseline [ Time Frame: Day 1 through Day 28 ]
• Minimal Concentration (Ctrough) of PF-07321332 [ Time Frame: Day 1 post dose, Day 5 pre dose ]
• All cause mortality in participants who have a negative RT-PCR result at baseline [ Time Frame: Day 1 through Day 38 ]
• Viral titers measured via RT-PCR in nasal swabs in participants who have a negative RT-PCR result at baseline [ Time Frame: Day 1 through Day 14 ]
• Number of days of hospital and intensive care unit stay in participants with COVID-19 related hospitalization who have a negative RT-PCR result at baseline [ Time Frame: Day 1 through Day 28 ]
• Number of COVID-19 related medical visits in participants who have a negative RT-PCR result at baseline [ Time Frame: Day 1 through Day 28 ]

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

Descriptive Information

• Brief Title: A Study of a Potential Oral Treatment to Prevent COVID-19 in Adults Who Are Exposed to Household Member(s) With a Confirmed Symptomatic COVID-19 Infection
• Official Title: A PHASE 2/3, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PLACEBO CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF 2 REGIMENS OF ORALLY ADMINISTERED PF 07321332/RITONAVIR IN PREVENTING SYMPTOMATIC SARS-COV-2 INFECTION IN ADULT HOUSEHOLD CONTACTS OF AN INDIVIDUAL WITH SYMPTOMATIC COVID-19

Brief Summary

The purpose of this clinical trial is to learn whether the study medicine prevent symptoms of COVID-19 in adults who have been exposed to household member(s) with a confirmed symptomatic COVID-19 infection.

All participants in the study will receive treatment for COVID-19 as needed, based on their regular doctor's recommendation. Two-thirds of participants will also receive two study medicines (PF-07321332 and ritonavir) by mouth twice a day for either five or ten days. We will compare the experiences of people receiving the study medicines to those of the people who do not. This will help us determine if the study medicines are safe and effective

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Eligible participants who are asymptomatic household contacts of an individual with symptomatic COVID-19 will be randomized (1:1:1) to receive orally every 12 hours:

PF-07321332/ritonavir for 5 days followed by placebo for 5 days or PF-07321332/ritonavir for 10 days or Placebo for 10 days

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double Blind Double Dummy

Primary Purpose: Prevention

• Condition: COVID-19

Intervention

• Drug: PF-07321332
  PF-07321332
• Drug: Placebo for PF-07321332
  Placebo
• Drug: Placebo for Ritonavir
  Placebo
• Drug: Ritonavir
  Ritonavir

Study Arms

• Experimental: PF-07321332/ritonavir (5 days)
  Participants will receive PF-07321332/ritonavir every 12 hours from Day 1 through Day 5 followed by Placebo every 12 hours from Day 6 through Day 10
  Interventions:

  • Drug: PF-07321332
  • Drug: Placebo for PF-07321332
  • Drug: Placebo for Ritonavir
  • Drug: Ritonavir
• Experimental: PF-07321332/ritonavir (10-Day)
  Participants will receive PF-07321332/ritonavir every 12 hours from Day 1 through Day 10.
  Interventions:

  • Drug: PF-07321332
  • Drug: Ritonavir
• Placebo Comparator: Placebo
  Participants will receive placebo every 12 hours from Day 1 through Day 10.
  Interventions:

  • Drug: Placebo for PF-07321332
  • Drug: Placebo for Ritonavir

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 8, 2022): 2954
• Original Estimated Enrollment (submitted: September 15, 2021): 2634
• Actual Study Completion Date: April 12, 2022
• Actual Primary Completion Date: April 12, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants who have a negative screening SARS-CoV-2 rapid antigen test result and who are asymptomatic household contacts with exposure within 96 hours to an individual who is symptomatic and recently tested positive for SARS CoV-2.
• Fertile participants must agree to use a highly effective method of contraception

Exclusion Criteria:

• History of SARS-CoV-2 infection in the past 6 months
• Experiencing measured fever (documented temperature >38˚C or 100.4˚F) or other signs or symptoms consistent with COVID-19
• Known medical history of active liver disease
• Chronic Kidney Disease or have known moderate to severe renal impairment.
• Known Human Immunodeficiency Virus (HIV) infection with viral load > 400 copies/ml within the last 6 months or taking prohibited medications for HIV treatment
• Suspected or confirmed concurrent active systemic infection
• Active cancer requiring treatment with prohibited medication.
• 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 approved, authorized, or investigational anti-SARS-CoV-2 mAb, convalescent plasma, other drugs for treatment of COVID-19, or other anti-SARS-CoV-2 biologic products within 6 months of screening
• Has received any SARS-CoV-2 vaccine within 6 months prior to screening or is expected to receive a SARS-CoV-2 vaccine or other approved, authorized, or investigational postexposure prophylaxis treatments through Day 38.
• Participating in another interventional clinical study with an investigational compound or device, including those for COVID-19
• Known or prior participation in this trial or another trial involving PF-07321332.
• 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, Malaysia, Mexico, Poland, Russian Federation, South Africa, Spain, Thailand, Turkey, Ukraine, United States
• Removed Location Countries: Korea, Republic of, Puerto Rico, Taiwan

Administrative Information

• NCT Number: NCT05047601
• Other Study ID Numbers: C4671006; 2021-002894-24 ( EudraCT Number ); EPIC-PEP ( 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: April 2023