A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir
AN INTERVENTIONAL, EFFICACY AND SAFETY, PHASE 2, RANDOMIZED, DOUBLE-BLIND, 2-ARM STUDY TO INVESTIGATE A REPEAT 5-DAY COURSE OF NIRMATRELVIR/RITONAVIR COMPARED TO PLACEBO/RITONAVIR IN PARTICIPANTS AT LEAST 12 YEARS OF AGE WITH REBOUND OF COVID-19 SYMPTOMS AND RAPID ANTIGEN TEST POSITIVITY
2 other identifiers
interventional
436
5 countries
84
Brief Summary
The purpose of this study is to learn about the safety and effects of nirmatrelvir/ritonavir for the potential treatment of COVID-19 rebound. The study is seeking participants who:
- Have completed treatment with nirmatrelvir/ritonavir
- Have a rebound in COVID-19 symptoms
- Are SARS-CoV-2 (COVID-19) positive All study medications will be taken 2 times a day by mouth for 5 days. The first dose of study medication is taken at the study clinic and the rest at home. We will examine the experiences of people receiving the study medicines to those who do not. This will help us determine if the study medicines are safe and effective. People taking part will be in this study for about 24 weeks. Enrolled participants will need to visit the study clinic at least 8 times during the study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 covid19
Started Oct 2022
Typical duration for phase_2 covid19
84 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 3, 2022
CompletedFirst Posted
Study publicly available on registry
October 5, 2022
CompletedStudy Start
First participant enrolled
October 19, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 27, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
February 9, 2024
CompletedResults Posted
Study results publicly available
October 8, 2024
CompletedOctober 8, 2024
September 1, 2024
11 months
October 3, 2022
September 17, 2024
September 17, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline to Day 5 in Viral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribonucleic Acid (RNA) Level in Nasopharyngeal (NP) Swabs: mITT Population
Baseline was defined as the latest measurement between Day -1 and Day 1, but post-dose samples that were collected within 1 hour post start of dosing were also treated as baseline. Samples with result "\< lower limit of quantification (LLOQ)" were imputed as 1.7 log10 copies/milliliter (mL), and samples with result "Not Detected" were imputed as 0.0 log10 copies/mL.
Baseline, Day 5
Secondary Outcomes (3)
Time to Two Consecutive Negative Rapid Antigen Test (RAT) Results At Least 24 Hours Apart Through Day 28: mITT Population
Day 1 of dosing maximum up to Day 28 or censoring date, whichever occurred first
Time to Sustained Alleviation of All Targeted Signs and Symptoms Through Day 28: mITT Population
Day 1 of dosing maximum up to Day 28 or censoring date, whichever occurred first
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation From Study
Day 1 of dosing up to maximum Week 24 follow-up
Study Arms (2)
nirmatrelvir plus ritonavir for 5 days
EXPERIMENTALNirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days
placebo plus ritonavir for 5 days
OTHERplacebo (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days
Interventions
Participants will receive 2 tablets of nirmatrelvir every 12 hours
Participants will receive 1 capsule of ritonavir every 12 hours
Participants will receive 2 tablets of placebo for nirmatrelvir every 12 hours. A placebo does not have any medicine in it but looks just like the medicine being studied.
Eligibility Criteria
You may qualify if:
- Documentation of nirmatrelvir/ritonavir treatment with patient-reported 100% compliance. Symptom alleviation or resolution in COVID-19 signs/symptoms followed by a worsening (rebound) of signs/symptoms after completing an initial 5-day course of nirmatrelvir/ritonavir
- Onset of rebound in COVID-19 symptoms within 2 weeks (14 days) after the completion of the initial 5-day course of nirmatrelvir/ritonavir.
- Onset of rebound in signs/symptoms attributable to COVID-19 within 48 hours prior to randomization and ≥1 sign/symptom attributable to COVID-19 present on the day of randomization.
- SARS-CoV-2 infection as determined by rapid antigen testing within 24 hours prior to randomization
- At least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19.
You may not qualify if:
- Current need for hospitalization, hospitalized for the COVID-19 infection or anticipated need for hospitalization within 24 hours after randomization
- History of severe chronic liver disease
- Receiving dialysis or have known age-specific estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (eCrCl) \<30 mL/min/1.73 m2 at screening as measured by a serum creatinine point of care device
- Oxygen saturation of \<92% on room air obtained at rest within 24 hours prior to randomization
- Immunocompromised.
- Current use of any prohibited concomitant medication(s)
- Females who are pregnant and \<14 weeks gestation
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (84)
The Institute for Liver Health dba Arizona Clinical Trials
Mesa, Arizona, 85210, United States
Abby's Research institute
Phoenix, Arizona, 85031, United States
Epic Medical Research - Surprise
Surprise, Arizona, 85378, United States
Smart Cures Clinical Research
Anaheim, California, 92806, United States
Hope Clinical Research, Inc.
Canoga Park, California, 91303, United States
Ascada Health PC dba Ascada Research
Fullerton, California, 92835, United States
Ascada Research
Fullerton, California, 92835, United States
Paradigm Clinical Research Centers, Inc
La Mesa, California, 91942, United States
CVS Health - 8876 - Long Beach
Long Beach, California, 90806, United States
Carbon Health - North Hollywood - NoHo West
North Hollywood, California, 91606, United States
Paradigm Clinical Research Centers, Inc
Wheat Ridge, Colorado, 80033, United States
Emerson Clinical Research Institute - Washington - Connecticut Avenue
Washington D.C., District of Columbia, 20009, United States
Emerson Clinical Research Institute
Washington D.C., District of Columbia, 20011, United States
Palm Harbor Dermatology PA d/b/a TrueBlue Clinical Research
Brandon, Florida, 33511, United States
Herco Medical and Research Center Inc
Coral Gables, Florida, 33134, United States
NeoClinical Research
Hialeah, Florida, 33016, United States
Sweet Hope Research Specialty, Inc
Hialeah, Florida, 33016, United States
Unlimited Medical Research Group LLC
Hialeah Gardens, Florida, 33018, United States
Asclepes Research Center - Spring Hill
Lutz, Florida, 33549, United States
LCC Medical Research Institute
Miami, Florida, 33126, United States
Premium Medical Research Corp
Miami, Florida, 33126, United States
Global Health Clinical Trials
Miami, Florida, 33135, United States
South Florida Research Center
Miami, Florida, 33135, United States
Reliant Medical Research
Miami, Florida, 33165, United States
Innova Pharma Research
Miami, Florida, 33175, United States
Entrust Clinical Research
Miami, Florida, 33176, United States
Reed Medical Research
Miami, Florida, 33176, United States
Kendall South Medical Center
Miami, Florida, 33185, United States
Pro-Care Research Center, Corp.
Miami Gardens, Florida, 33014, United States
Omega Research Orlando
Orlando, Florida, 32808, United States
NAPA Research
Pompano Beach, Florida, 33064, United States
Asclepes Research Center - Spring Hill
Spring Hill, Florida, 34609, United States
GCP Research, Global Clinical professionals
St. Petersburg, Florida, 33705, United States
Theia Clinical Research - 5th Avenue North
St. Petersburg, Florida, 33710, United States
Palm Harbor Dermatology PA d/b/a TrueBlue Clinical Research
Tampa, Florida, 33609, United States
Santos Research Center
Tampa, Florida, 33615, United States
Clinical Site Partners, LLC dba CSP Orlando
Winter Park, Florida, 32789, United States
Clinical Site Partners, LLC dba Flourish Research
Winter Park, Florida, 32789, United States
Bingham Memorial Hospital
Blackfoot, Idaho, 83221, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Centennial Medical Group
Elkridge, Maryland, 21075, United States
University of Massachusetts Chan Medical School
Worcester, Massachusetts, 01655, United States
Great Lakes Research Group, Inc.
Bay City, Michigan, 48706, United States
C.S. Mott Clinical Research Center (CRC)
Detroit, Michigan, 48201, United States
Beaumont Infectious Diseases Research
Royal Oak, Michigan, 48073, United States
Olive Branch Family Medical Center
Olive Branch, Mississippi, 38654, United States
Mercury Street Medical Group, PLLC
Butte, Montana, 59701, United States
Excel Clinical Research, LLC
Las Vegas, Nevada, 89109, United States
CVS Health - Site 02815 East Brunswick
East Brunswick, New Jersey, 08816, United States
Hackensack Meridian Jersey Shore University Medical Center
Neptune City, New Jersey, 07753, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Onsite Clinical Solutions (secondary location)
Charlotte, North Carolina, 28208, United States
OnSite Clinical Solutions
Charlotte, North Carolina, 28208, United States
Accellacare - Wilmington
Wilmington, North Carolina, 28401, United States
WellNow Urgent Care and Research - Columbus
Columbus, Ohio, 43214, United States
Willamette Valley Clinical Studies
Eugene, Oregon, 97404, United States
Heritage Valley Multispecialty Group, Inc
Beaver, Pennsylvania, 15009, United States
Premier Primary Care
Union City, Tennessee, 38261, United States
Nayak Research, LLC
Andrews, Texas, 79714, United States
Headlands Research - Brownsville
Brownsville, Texas, 78526, United States
Southwest Family Medicine Associates
Dallas, Texas, 75235, United States
Next Innovative Clinical Research
Houston, Texas, 77021, United States
Next Level Urgent Care
Houston, Texas, 77057, United States
Accurate Clinical Research - East Humble
Humble, Texas, 77338, United States
Accurate Clinical Research, Inc
Humble, Texas, 77338, United States
Sun Research Institute
San Antonio, Texas, 78215, United States
Eastside Research Associates
Redmond, Washington, 98052, United States
Dawson Clinical Research
Guelph, Ontario, N1H 1B1, Canada
Hamilton Medical Research Group
Hamilton, Ontario, L8M 1K7, Canada
Medical Trust Clinics
Oshawa, Ontario, L1G 4T3, Canada
Winchester District Memorial Hospital
Winchester, Ontario, K0C 2K0, Canada
Thoracic General Hospital of Athens "I Sotiria"
Athens, Attica, 11527, Greece
Evangelismos General Hospital of Athens
Athens, Attikí, 106 76, Greece
Alexandra General Hospital of Athens
Athens, Attikí, 115 28, Greece
General Hospital of Athens "Laiko"
Athens, 11527, Greece
AHEPA University General Hospital of Thessaloniki
Thessaloniki, 54636, Greece
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, Lombardy, 20122, Italy
ASST Fatebenefratelli Sacco
Milan, Milano, 20157, Italy
A.O.U. Policlinico Paolo Giaccone
Palermo, Sicily, 90129, Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100, Italy
Far Eastern Memorial Hospital
New Taipei City, NEW Taipei, 220, Taiwan
Taichung Veterans General Hospital
Taichung, 407, Taiwan
National Taiwan University Hospital
Taipei, 10002, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Related Publications (2)
Zhang W, Terra SG, Weinstein EA, Bramson C, Leister-Tebbe H, Baniecki ML, Guan S, Agyemang A, Antonucci S, Wisemandle W, Hammond J. Retreatment With Nirmatrelvir/Ritonavir Following Return of COVID-19 Symptoms and SARS-CoV-2 Positivity. Clin Infect Dis. 2025 Sep 30:ciaf548. doi: 10.1093/cid/ciaf548. Online ahead of print.
PMID: 41027009DERIVEDBaniecki ML, Guan S, Rai DK, Yang Q, Lee JT, Hao L, Weinstein E, Hyde C, Cardin RD, Soares H, Hammond J. Integrated virologic analysis of resistance to nirmatrelvir/ritonavir in individuals across four phase 2/3 clinical studies for the treatment of COVID-19. EBioMedicine. 2025 Aug;118:105819. doi: 10.1016/j.ebiom.2025.105819. Epub 2025 Jun 30.
PMID: 40592258DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 3, 2022
First Posted
October 5, 2022
Study Start
October 19, 2022
Primary Completion
September 27, 2023
Study Completion
February 9, 2024
Last Updated
October 8, 2024
Results First Posted
October 8, 2024
Record last verified: 2024-09
Data Sharing
- IPD Sharing
- Will share
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.