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

Pfizer436 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

436

Conditions

COVID-19

Interventions

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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

Locations (84)

The Institute for Liver Health dba Arizona Clinical Trials

Mesa, Arizona, United States

Abby's Research institute

Phoenix, Arizona, United States

Epic Medical Research - Surprise

Surprise, Arizona, United States

Smart Cures Clinical Research

Anaheim, California, United States

Hope Clinical Research, Inc.

Canoga Park, California, United States

Outcomes

Primary Outcomes

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.

Time frame: Baseline, Day 5

Secondary Outcomes

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).

Time frame: 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

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.

Time frame: 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

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.

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