AzTrials
AzTrials

COVID-19Phase 2NCT05567952

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

A Phase 2 study testing nirmatrelvir and ritonavir in people with COVID-19, run by Pfizer at 84 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
COVID-19
What is being tested?
nirmatrelvir and ritonavir
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
436 participants
Where
84 sitesin 5 countries
Study dates
19 Oct 2022to 9 Feb 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

84 sites in 5 countries.

84 sites in 5 countries

United States67 sites

  • Smart Cures Clinical Research

    Anaheim, California, 92806

  • Nayak Research, LLC

    Andrews, Texas, 79714

  • Great Lakes Research Group, Inc.

    Bay City, Michigan, 48706

  • Heritage Valley Multispecialty Group, Inc

    Beaver, Pennsylvania, 15009

  • Bingham Memorial Hospital

    Blackfoot, Idaho, 83221

  • Palm Harbor Dermatology PA d/b/a TrueBlue Clinical Research

    Brandon, Florida, 33511

  • Headlands Research - Brownsville

    Brownsville, Texas, 78526

  • Mercury Street Medical Group, PLLC

    Butte, Montana, 59701

  • Hope Clinical Research, Inc.

    Canoga Park, California, 91303

  • Onsite Clinical Solutions (secondary location)

    Charlotte, North Carolina, 28208

  • OnSite Clinical Solutions

    Charlotte, North Carolina, 28208

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • WellNow Urgent Care and Research - Columbus

    Columbus, Ohio, 43214

  • Herco Medical and Research Center Inc

    Coral Gables, Florida, 33134

  • Southwest Family Medicine Associates

    Dallas, Texas, 75235

  • C.S. Mott Clinical Research Center (CRC)

    Detroit, Michigan, 48201

  • CVS Health - Site 02815 East Brunswick

    East Brunswick, New Jersey, 08816

  • Centennial Medical Group

    Elkridge, Maryland, 21075

  • Willamette Valley Clinical Studies

    Eugene, Oregon, 97404

  • Ascada Health PC dba Ascada Research

    Fullerton, California, 92835

  • Ascada Research

    Fullerton, California, 92835

  • NeoClinical Research

    Hialeah, Florida, 33016

  • Sweet Hope Research Specialty, Inc

    Hialeah, Florida, 33016

  • Unlimited Medical Research Group LLC

    Hialeah Gardens, Florida, 33018

  • Next Innovative Clinical Research

    Houston, Texas, 77021

  • Next Level Urgent Care

    Houston, Texas, 77057

  • Accurate Clinical Research - East Humble

    Humble, Texas, 77338

  • Accurate Clinical Research, Inc

    Humble, Texas, 77338

  • Paradigm Clinical Research Centers, Inc

    La Mesa, California, 91942

  • Excel Clinical Research, LLC

    Las Vegas, Nevada, 89109

  • CVS Health - 8876 - Long Beach

    Long Beach, California, 90806

  • Asclepes Research Center - Spring Hill

    Lutz, Florida, 33549

  • The Institute for Liver Health dba Arizona Clinical Trials

    Mesa, Arizona, 85210

  • LCC Medical Research Institute

    Miami, Florida, 33126

  • Premium Medical Research Corp

    Miami, Florida, 33126

  • Global Health Clinical Trials

    Miami, Florida, 33135

  • South Florida Research Center

    Miami, Florida, 33135

  • Reliant Medical Research

    Miami, Florida, 33165

  • Innova Pharma Research

    Miami, Florida, 33175

  • Entrust Clinical Research

    Miami, Florida, 33176

  • Reed Medical Research

    Miami, Florida, 33176

  • Kendall South Medical Center

    Miami, Florida, 33185

  • Pro-Care Research Center, Corp.

    Miami Gardens, Florida, 33014

  • Hackensack Meridian Jersey Shore University Medical Center

    Neptune City, New Jersey, 07753

  • Carbon Health - North Hollywood - NoHo West

    North Hollywood, California, 91606

  • Olive Branch Family Medical Center

    Olive Branch, Mississippi, 38654

  • Omega Research Orlando

    Orlando, Florida, 32808

  • Abby's Research institute

    Phoenix, Arizona, 85031

  • NAPA Research

    Pompano Beach, Florida, 33064

  • Eastside Research Associates

    Redmond, Washington, 98052

  • Beaumont Infectious Diseases Research

    Royal Oak, Michigan, 48073

  • Sun Research Institute

    San Antonio, Texas, 78215

  • Asclepes Research Center - Spring Hill

    Spring Hill, Florida, 34609

  • GCP Research, Global Clinical professionals

    St. Petersburg, Florida, 33705

  • Theia Clinical Research - 5th Avenue North

    St. Petersburg, Florida, 33710

  • Epic Medical Research - Surprise

    Surprise, Arizona, 85378

  • Palm Harbor Dermatology PA d/b/a TrueBlue Clinical Research

    Tampa, Florida, 33609

  • Santos Research Center

    Tampa, Florida, 33615

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Premier Primary Care

    Union City, Tennessee, 38261

  • Emerson Clinical Research Institute - Washington - Connecticut Avenue

    Washington D.C., District of Columbia, 20009

  • Emerson Clinical Research Institute

    Washington D.C., District of Columbia, 20011

  • Paradigm Clinical Research Centers, Inc

    Wheat Ridge, Colorado, 80033

  • Accellacare - Wilmington

    Wilmington, North Carolina, 28401

  • Clinical Site Partners, LLC dba CSP Orlando

    Winter Park, Florida, 32789

  • Clinical Site Partners, LLC dba Flourish Research

    Winter Park, Florida, 32789

  • University of Massachusetts Chan Medical School

    Worcester, Massachusetts, 01655

Other trials in United States

Greece5 sites

  • Thoracic General Hospital of Athens "I Sotiria"

    Athens, Attica, 11527

  • Evangelismos General Hospital of Athens

    Athens, Attikí, 106 76

  • Alexandra General Hospital of Athens

    Athens, Attikí, 115 28

  • General Hospital of Athens "Laiko"

    Athens, 11527

  • AHEPA University General Hospital of Thessaloniki

    Thessaloniki, 54636

Other trials in Greece

Canada4 sites

  • Dawson Clinical Research

    Guelph, Ontario, N1H 1B1

  • Hamilton Medical Research Group

    Hamilton, Ontario, L8M 1K7

  • Medical Trust Clinics

    Oshawa, Ontario, L1G 4T3

  • Winchester District Memorial Hospital

    Winchester, Ontario, K0C 2K0

Other trials in Canada

Italy4 sites

  • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

    Milan, Lombardy, 20122

  • ASST Fatebenefratelli Sacco

    Milan, Milano, 20157

  • A.O.U. Policlinico Paolo Giaccone

    Palermo, Sicily, 90129

  • Fondazione IRCCS Policlinico San Matteo

    Pavia, 27100

Other trials in Italy

Taiwan4 sites

  • Far Eastern Memorial Hospital

    New Taipei City, NEW Taipei, 220

  • Taichung Veterans General Hospital

    Taichung, 407

  • National Taiwan University Hospital

    Taipei, 10002

  • Taipei Veterans General Hospital

    Taipei, 11217

Other trials in Taiwan

About this study

Official title: 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

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:

Read more
  • 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.

Conditions
COVID-19
Being tested
nirmatrelvir, ritonavir, placebo for nirmatrelvir
Keywords
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronavirus disease 2019 (COVID-19), COVID-19 rebound, Paxlovid, Nirmatrelvir
Medical subject headings
COVID-19, COVID-19 rebound

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nirmatrelvirDrug

    Participants will receive 2 tablets of nirmatrelvir every 12 hours

  • ritonavirDrug

    Participants will receive 1 capsule of ritonavir every 12 hours

  • placebo for nirmatrelvirDrug

    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.

Study groups in NCT05567952
Study groupRoleWhat they receive
nirmatrelvir plus ritonavir for 5 daysExperimentalNirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days
Receives: Drug: nirmatrelvir; Drug: ritonavir
placebo plus ritonavir for 5 daysOtherplacebo (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days
Receives: Drug: ritonavir; Drug: placebo for nirmatrelvir

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, Day 5

Secondary outcomes (3)

  1. Time to Two Consecutive Negative Rapid Antigen Test (RAT) Results At Least 24 Hours Apart Through Day 28: mITT Population

    The event of 2 consecutive negative RAT results obtained at least 24 (-2) hours apart through Day 28 was defined as achieving 2 consecutive non-missing RATs with negative results through Day 28, where the 2 tests were at least 22 hours and at most 7 days apart. For the event of 2 consecutive negative RAT results obtained at least 24 hours apart through Day 28, the date of the first negative RAT result was considered the first event date. Time to 2 consecutive negative RAT results obtained at least 24 hours apart defined as: for participant achieving event, time to event = (first event date) -(first dose date) + 1. For participant not achieving event (censored), censoring date was at last date of RAT measurement, time = (censoring date) - (first dose date) + 1 or Day 27 whichever occurred first (Day 27 was last possible day to achieve 2 consecutive negative RAT results obtained at least 24 hours apart through Day 28).

    Measured: Day 1 of dosing maximum up to Day 28 or censoring date, whichever occurred first

  2. Time to Sustained Alleviation of All Targeted Signs and Symptoms Through Day 28: mITT Population

    Sustained alleviation of all targeted COVID-19 signs/symptoms was defined as the event occurring on the first of 2 consecutive days when all symptoms scored as moderate or severe at study entry are scored as mild or absent and all symptoms scored mild or absent at study entry are scored as absent. The first day of the 2 consecutive-day period was considered the first event date. The time to sustained symptom alleviation was defined as for a participant with sustained symptom alleviation, time to event was calculated as (First Event Date) - (First Dose Date) +1. For a participant that either completed Day 28 of the study or discontinued from the study before Day 28 without sustained symptom alleviation (censored), censoring date was at the last date on which symptom alleviation was assessed, and time was calculated as (Censoring Date) - (First Dose Date) +1 or Day 27 whichever occurred first.

    Measured: Day 1 of dosing maximum up to Day 28 or censoring date, whichever occurred first

  3. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation From Study

    An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening (risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or nonpathogenic. TEAEs were defined as AE that started on or after study medication on Day 1 up to Week 24 follow-up. AEs included both SAEs and all non-SAEs.

    Measured: Day 1 of dosing up to maximum Week 24 follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2022
  2. Study start19 Oct 2022
  3. Primary completion27 Sep 2023
  4. Study completion9 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
436 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05567952
Sponsor's protocol ID
C4671042
Other IDs
2022-002827-36
Status last verified
Sep 2024
First submitted
3 Oct 2022
Last updated
8 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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. 2026 Feb 9;82(1):e33-e40. doi: 10.1093/cid/ciaf548.

    PubMed 41027009

  • Baniecki 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.

    PubMed 40592258

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing nirmatrelvir and ritonavir in people with COVID-19, run by Pfizer at 84 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 84 sites in United States, Greece, Canada, Italy, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Baseline, Day 5). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05567952, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2024.

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