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

NCT ID: NCT05567952

Last Updated: 2024-10-08

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

436 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-19

Study Completion Date

2024-02-09

Brief Summary

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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.

Detailed Description

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Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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nirmatrelvir plus ritonavir for 5 days

Nirmatrelvir (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days

Group Type EXPERIMENTAL

nirmatrelvir

Intervention Type DRUG

Participants will receive 2 tablets of nirmatrelvir every 12 hours

ritonavir

Intervention Type DRUG

Participants will receive 1 capsule of ritonavir every 12 hours

placebo plus ritonavir for 5 days

placebo (2 tablets) plus ritonavir (1 capsule) will be given by mouth every 12 hours for 5 days

Group Type OTHER

ritonavir

Intervention Type DRUG

Participants will receive 1 capsule of ritonavir every 12 hours

placebo for nirmatrelvir

Intervention Type DRUG

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.

Interventions

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nirmatrelvir

Participants will receive 2 tablets of nirmatrelvir every 12 hours

Intervention Type DRUG

ritonavir

Participants will receive 1 capsule of ritonavir every 12 hours

Intervention Type DRUG

placebo for nirmatrelvir

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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The Institute for Liver Health dba Arizona Clinical Trials

Mesa, Arizona, United States

Site Status

Abby's Research institute

Phoenix, Arizona, United States

Site Status

Epic Medical Research - Surprise

Surprise, Arizona, United States

Site Status

Smart Cures Clinical Research

Anaheim, California, United States

Site Status

Hope Clinical Research, Inc.

Canoga Park, California, United States

Site Status

Ascada Health PC dba Ascada Research

Fullerton, California, United States

Site Status

Ascada Research

Fullerton, California, United States

Site Status

Paradigm Clinical Research Centers, Inc

La Mesa, California, United States

Site Status

CVS Health - 8876 - Long Beach

Long Beach, California, United States

Site Status

Carbon Health - North Hollywood - NoHo West

North Hollywood, California, United States

Site Status

Paradigm Clinical Research Centers, Inc

Wheat Ridge, Colorado, United States

Site Status

Emerson Clinical Research Institute - Washington - Connecticut Avenue

Washington D.C., District of Columbia, United States

Site Status

Emerson Clinical Research Institute

Washington D.C., District of Columbia, United States

Site Status

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

Brandon, Florida, United States

Site Status

Herco Medical and Research Center Inc

Coral Gables, Florida, United States

Site Status

NeoClinical Research

Hialeah, Florida, United States

Site Status

Sweet Hope Research Specialty, Inc

Hialeah, Florida, United States

Site Status

Unlimited Medical Research Group LLC

Hialeah Gardens, Florida, United States

Site Status

Asclepes Research Center - Spring Hill

Lutz, Florida, United States

Site Status

LCC Medical Research Institute

Miami, Florida, United States

Site Status

Premium Medical Research Corp

Miami, Florida, United States

Site Status

Global Health Clinical Trials

Miami, Florida, United States

Site Status

South Florida Research Center

Miami, Florida, United States

Site Status

Reliant Medical Research

Miami, Florida, United States

Site Status

Innova Pharma Research

Miami, Florida, United States

Site Status

Entrust Clinical Research

Miami, Florida, United States

Site Status

Reed Medical Research

Miami, Florida, United States

Site Status

Kendall South Medical Center

Miami, Florida, United States

Site Status

Pro-Care Research Center, Corp.

Miami Gardens, Florida, United States

Site Status

Omega Research Orlando

Orlando, Florida, United States

Site Status

NAPA Research

Pompano Beach, Florida, United States

Site Status

Asclepes Research Center - Spring Hill

Spring Hill, Florida, United States

Site Status

GCP Research, Global Clinical professionals

St. Petersburg, Florida, United States

Site Status

Theia Clinical Research - 5th Avenue North

St. Petersburg, Florida, United States

Site Status

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

Tampa, Florida, United States

Site Status

Santos Research Center

Tampa, Florida, United States

Site Status

Clinical Site Partners, LLC dba CSP Orlando

Winter Park, Florida, United States

Site Status

Clinical Site Partners, LLC dba Flourish Research

Winter Park, Florida, United States

Site Status

Bingham Memorial Hospital

Blackfoot, Idaho, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Centennial Medical Group

Elkridge, Maryland, United States

Site Status

University of Massachusetts Chan Medical School

Worcester, Massachusetts, United States

Site Status

Great Lakes Research Group, Inc.

Bay City, Michigan, United States

Site Status

C.S. Mott Clinical Research Center (CRC)

Detroit, Michigan, United States

Site Status

Beaumont Infectious Diseases Research

Royal Oak, Michigan, United States

Site Status

Olive Branch Family Medical Center

Olive Branch, Mississippi, United States

Site Status

Mercury Street Medical Group, PLLC

Butte, Montana, United States

Site Status

Excel Clinical Research, LLC

Las Vegas, Nevada, United States

Site Status

CVS Health - Site 02815 East Brunswick

East Brunswick, New Jersey, United States

Site Status

Hackensack Meridian Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Onsite Clinical Solutions (secondary location)

Charlotte, North Carolina, United States

Site Status

OnSite Clinical Solutions

Charlotte, North Carolina, United States

Site Status

Accellacare - Wilmington

Wilmington, North Carolina, United States

Site Status

WellNow Urgent Care and Research - Columbus

Columbus, Ohio, United States

Site Status

Willamette Valley Clinical Studies

Eugene, Oregon, United States

Site Status

Heritage Valley Multispecialty Group, Inc

Beaver, Pennsylvania, United States

Site Status

Premier Primary Care

Union City, Tennessee, United States

Site Status

Nayak Research, LLC

Andrews, Texas, United States

Site Status

Headlands Research - Brownsville

Brownsville, Texas, United States

Site Status

Southwest Family Medicine Associates

Dallas, Texas, United States

Site Status

Next Innovative Clinical Research

Houston, Texas, United States

Site Status

Next Level Urgent Care

Houston, Texas, United States

Site Status

Accurate Clinical Research - East Humble

Humble, Texas, United States

Site Status

Accurate Clinical Research, Inc

Humble, Texas, United States

Site Status

Sun Research Institute

San Antonio, Texas, United States

Site Status

Eastside Research Associates

Redmond, Washington, United States

Site Status

Dawson Clinical Research

Guelph, Ontario, Canada

Site Status

Hamilton Medical Research Group

Hamilton, Ontario, Canada

Site Status

Medical Trust Clinics

Oshawa, Ontario, Canada

Site Status

Winchester District Memorial Hospital

Winchester, Ontario, Canada

Site Status

Thoracic General Hospital of Athens "I Sotiria"

Athens, Attica, Greece

Site Status

Evangelismos General Hospital of Athens

Athens, Attikí, Greece

Site Status

Alexandra General Hospital of Athens

Athens, Attikí, Greece

Site Status

General Hospital of Athens "Laiko"

Athens, , Greece

Site Status

AHEPA University General Hospital of Thessaloniki

Thessaloniki, , Greece

Site Status

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

Site Status

ASST Fatebenefratelli Sacco

Milan, Milano, Italy

Site Status

A.O.U. Policlinico Paolo Giaccone

Palermo, Sicily, Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

Far Eastern Memorial Hospital

New Taipei City, NEW Taipei, Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Countries

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United States Canada Greece Italy Taiwan

References

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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.

Reference Type DERIVED
PMID: 41027009 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40592258 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C4671042

To obtain contact information for a study center near you, click here.

Other Identifiers

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2022-002827-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C4671042

Identifier Type: -

Identifier Source: org_study_id

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