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

Phase 2

Completed

Conditions: COVID-19

Interventions: Drug: nirmatrelvir
Drug: ritonavir
Drug: placebo for nirmatrelvir

Registration Number: NCT05567952

Lead Sponsor: Pfizer

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 436

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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, Day 5	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.

Secondary Outcome Measures

Name	Time	Method
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	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).
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	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.
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	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.

Trial Locations

Locations (81): University of Massachusetts Chan Medical School
🇺🇸
Worcester, Massachusetts, United States
Mercury Street Medical Group, PLLC
🇺🇸
Butte, Montana, United States
Global Health Clinical Trials
🇺🇸
Miami, Florida, United States
South Florida Research Center
🇺🇸
Miami, Florida, United States
Reliant Medical Research
🇺🇸
Miami, Florida, United States
Reed Medical Research
🇺🇸
Miami, Florida, United States
Premium Medical Research Corp
🇺🇸
Miami, Florida, United States
Kendall South Medical Center
🇺🇸
Miami, Florida, United States
Innova Pharma Research
🇺🇸
Miami, Florida, United States
Entrust Clinical Research
🇺🇸
Miami, Florida, United States
Excel Clinical Research, LLC
🇺🇸
Las Vegas, Nevada, United States
Sun Research Institute
🇺🇸
San Antonio, Texas, United States
Hope Clinical Research, Inc.
🇺🇸
Canoga Park, California, United States
Smart Cures Clinical Research
🇺🇸
Anaheim, California, United States
Ascada Research
🇺🇸
Fullerton, California, United States
The Institute for Liver Health dba Arizona Clinical Trials
🇺🇸
Mesa, Arizona, United States
Herco Medical and Research Center Inc
🇺🇸
Coral Gables, Florida, United States
Epic Medical Research - Surprise
🇺🇸
Surprise, Arizona, United States
Paradigm Clinical Research Centers, Inc
🇺🇸
Wheat Ridge, Colorado, United States
Ascada Health PC dba Ascada Research
🇺🇸
Fullerton, California, United States
Carbon Health - North Hollywood - NoHo West
🇺🇸
North Hollywood, California, United States
WellNow Urgent Care and Research - Columbus
🇺🇸
Columbus, Ohio, United States
OnSite Clinical Solutions
🇺🇸
Charlotte, North Carolina, United States
Emerson Clinical Research Institute
🇺🇸
Washington, District of Columbia, United States
Unlimited Medical Research Group LLC
🇺🇸
Hialeah Gardens, Florida, United States
LCC Medical Research Institute
🇺🇸
Miami, Florida, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
Centennial Medical Group
🇺🇸
Elkridge, Maryland, United States
Hackensack Meridian Jersey Shore University Medical Center
🇺🇸
Neptune, New Jersey, United States
Great Lakes Research Group, Inc.
🇺🇸
Bay City, Michigan, United States
Willamette Valley Clinical Studies
🇺🇸
Eugene, Oregon, United States
Onsite Clinical Solutions (secondary location)
🇺🇸
Charlotte, North Carolina, United States
Heritage Valley Multispecialty Group, Inc
🇺🇸
Beaver, Pennsylvania, United States
Next Innovative Clinical Research
🇺🇸
Houston, Texas, United States
Accurate Clinical Research, Inc
🇺🇸
Humble, Texas, United States
Taipei Veterans General Hospital
🇨🇳
Taipei, Taiwan
Next Level Urgent Care
🇺🇸
Houston, Texas, United States
Nayak Research, LLC
🇺🇸
Andrews, Texas, United States
A.O.U. Policlinico Paolo Giaccone
🇮🇹
Palermo, Sicilia, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹
Pavia, Italy
Premier Primary Care
🇺🇸
Union City, Tennessee, United States
Southwest Family Medicine Associates
🇺🇸
Dallas, Texas, United States
Winchester District Memorial Hospital
🇨🇦
Winchester, Ontario, Canada
Thoracic General Hospital of Athens "I Sotiria"
🇬🇷
Athens, Attica, Greece
Alexandra General Hospital of Athens
🇬🇷
Athens, Attikí, Greece
Hamilton Medical Research Group
🇨🇦
Hamilton, Ontario, Canada
Medical Trust Clinics
🇨🇦
Oshawa, Ontario, Canada
Far Eastern Memorial Hospital
🇨🇳
New Taipei City, NEW Taipei, Taiwan
CVS Health - 8876 - Long Beach
🇺🇸
Long Beach, California, United States
Accellacare - Wilmington
🇺🇸
Wilmington, North Carolina, United States
Eastside Research Associates
🇺🇸
Redmond, Washington, United States
GCP Research, Global Clinical professionals
🇺🇸
Saint Petersburg, Florida, United States
Asclepes Research Center - Spring Hill
🇺🇸
Spring Hill, Florida, United States
Emerson Clinical Research Institute - Washington - Connecticut Avenue
🇺🇸
Washington, District of Columbia, United States
NAPA Research
🇺🇸
Pompano Beach, Florida, United States
Bingham Memorial Hospital
🇺🇸
Blackfoot, Idaho, United States
Headlands Research - Brownsville
🇺🇸
Brownsville, Texas, United States
Accurate Clinical Research - East Humble
🇺🇸
Humble, Texas, United States
Evangelismos General Hospital of Athens
🇬🇷
Athens, Attikí, Greece
Dawson Clinical Research
🇨🇦
Guelph, Ontario, Canada
General Hospital of Athens "Laiko"
🇬🇷
Athens, Greece
AHEPA University General Hospital of Thessaloniki
🇬🇷
Thessaloniki, Greece
ASST Fatebenefratelli Sacco
🇮🇹
Milan, Milano, Italy
Taichung Veterans General Hospital
🇨🇳
Taichung, Taiwan
Pro-Care Research Center, Corp.
🇺🇸
Miami Gardens, Florida, United States
NeoClinical Research
🇺🇸
Hialeah, Florida, United States
Sweet Hope Research Specialty, Inc
🇺🇸
Hialeah, Florida, United States
Abby's Research institute
🇺🇸
Phoenix, Arizona, United States
Theia Clinical Research - 5th Avenue North
🇺🇸
Saint Petersburg, Florida, United States
Clinical Site Partners, LLC dba CSP Orlando
🇺🇸
Winter Park, Florida, United States
Clinical Site Partners, LLC dba Flourish Research
🇺🇸
Winter Park, Florida, United States
C.S. Mott Clinical Research Center (CRC)
🇺🇸
Detroit, Michigan, United States
Beaumont Infectious Diseases Research
🇺🇸
Royal Oak, Michigan, United States
Olive Branch Family Medical Center
🇺🇸
Olive Branch, Mississippi, United States
CVS Health - Site 02815 East Brunswick
🇺🇸
East Brunswick, New Jersey, United States
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
🇮🇹
Milano, Lombardia, Italy
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Palm Harbor Dermatology PA d/b/a TrueBlue Clinical Research
🇺🇸
Tampa, Florida, United States
Omega Research Orlando
🇺🇸
Orlando, Florida, United States
Santos Research Center
🇺🇸
Tampa, Florida, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States