This is a Phase 3, randomized, actively controlled, double-blinded, double-dummy, superiority study to evaluate the efficacy and safety of ibuzatrelvir alone and in combination with remdesivir IV compared to remdesivir IV alone for the treatment of symptomatic COVID-19 in severely immunocompromised adult participants who are non-hospitalized or are hospitalized for observation or study intervention administration but do not require supplemental oxygen for COVID-19.
The purpose of this clinical trial is to learn about a study medicine called Ibuzatrelvir for the possible treatment of COVID-19 in immunocompromised patients. Immunocompromised patients with COVID-19 have more difficulty fighting infections and are at risk for persistent infections and progression to severe illness. This patient population may benefit from extended antiviral treatment durations, or a combination of antiviral therapies. This study will evaluate the efficacy and safety of ibuzatrelvir with and without remdesivir compared with remdesivir alone for the treatment of symptomatic COVID-19 in adult participants who are severely immunocompromised. The study is seeking adult male and female participants who: * Have a confirmed COVID-19 infection * Are severely immunocompromised due to blood cancers, organ transplant, certain medications or therapies * Have experienced the onset of signs or symptoms of COVID-19 within the past 5 days and are currently experiencing at least one of them. All of the participants in this study will receive active treatment for COVID-19, and will be randomized to one of three treatment arms. One-third will received remdesivir, one-third will receive ibuzatrelvir, and one third will receive both remdesivir and ibuzatrelvir. Ibuzatrelvir will be taken by mouth twice daily, and remdesivir is given as an IV infusion daily. Placebos that look like the study medicines but do not have any medication will be given to make the 3 treatment arms appear to be the same. The study will compare the experiences of people receiving ibuzatrelvir with and without remdesivir to those of the people who only received remdesivir for COVID-19. This will help decide if ibuzatrelvir is safe and effective. Participants will attend about 10 study visits over 24 weeks. During this time, they will have: * visits at the study clinic * blood work * swabs of the nose that are collected in the clinic and also by participants at home * questionnaires
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
The difference in the proportion of patients meeting the primary composite endpoint, between ibuzatrelvir and remdesivir vs remdesivir groups in symptomatic adult participants with COVID-19 who are severely immunocompromised
The difference in the proportion of participants with the composite endpoint of a) COVID-19-related ED visits with administration of supplemental oxygen, COVID-19 antiviral, or IV treatment; COVID-19-related hospitalization; or all-cause mortality, and b) Evidence of recurrent or persistent SARS-CoV-2 infection
Time frame: 38 days
Time to sustained alleviation of all targeted COVID-19 symptoms
The difference in median time to sustained alleviation of all targeted symptoms. Symptoms will be assessed through a daily electronic diary and include sore throat, cough, fever and diarrhea, among others.
Time frame: 38 days
Proportion of participants with evidence of recurrent or persistent SARS-CoV-2 infection.
The viral load is measured in nasal or nasopharyngeal samples using reverse transcription polymerase chain reaction (RT-PCR)
Time frame: 38 days
Proportion of participants with COVID-19-related ED visits with administration of supplemental oxygen, COVID-19 antiviral, or IV treatment, COVID-19-related hospitalization, or all-cause mortality.
Proportion of participants with COVID-19-related ED visits with administration of supplemental oxygen, COVID-19 antiviral, or IV treatment (eg, hydration, antibiotics, or corticosteroids), COVID-19-related hospitalization, or all-cause mortality.
Time frame: 38 days
Change from baseline in SARS-CoV-2 RNA level in NP or nasal swabs over time
The viral load is measured in nasal or nasopharyngeal samples using reverse transcription polymerase chain reaction (RT-PCR)
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Purpose
TREATMENT
Masking
TRIPLE
Enrollment
300
injection, for intravenous use
Hope Clinical Research, Inc.
Canoga Park, California, United States
RECRUITINGAmicis Research Center - Granada Hills
Granada Hills, California, United States
NOT_YET_RECRUITINGUC Davis CTSC Clinical Research Center
Sacramento, California, United States
RECRUITINGUniversity of California Davis Health
Sacramento, California, United States
RECRUITINGUCHealth Anschutz Inpatient Pavilion - Anschutz Medical Campus
Aurora, Colorado, United States
RECRUITINGUniversity of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
RECRUITINGUniversity of Colorado Clinical and Translational Research Center
Aurora, Colorado, United States
RECRUITINGUniversity of Colorado Hospital
Aurora, Colorado, United States
RECRUITINGGeorgetown University Medical Center
Washington D.C., District of Columbia, United States
RECRUITINGBRP- Hialeah Hospital
Hialeah, Florida, United States
NOT_YET_RECRUITING...and 105 more locations
Time frame: 38 days
Proportion of participants with SARS-CoV-2 NP or nasal RNA <LLOQ at each time point
Proportion of participants with a SARS-CoV-2 viral load below the lower limit of quantification (LLOQ) of the assay used to measure it.
Time frame: 38 days
Proportion of participants with viral rebound in SARS-CoV-2 RNA level in NP or nasal swabs
Virologic rebound is defined as: * Viral RNA is not detectable at the end of treatment, and later is detectable through Day 38 * Viral RNA is detected at end of treatment, and viral RNA levels increase further through Day 38
Time frame: 38 days
Time to sustained NP or nasal swab SARS-CoV-2 RNA <LLOQ
The time it takes for the viral RNA to no longer be detectable in a sample
Time frame: 38 days
Incidence of Treatment emergent adverse events, serious adverse events, and adverse events leading to discontinuation
An adverse event (AE) is any untoward medical occurrence in a participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. Serious adverse event (SAE) is any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect; a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical events. AEs included both SAEs and all non-SAEs. An AE is considered as TEAE if the event started on or after start date of study intervention.
Time frame: 38 days