COVID-19 Infection
Conditions
Keywords
COVID-19 infection, pneumonia, respiratory tract infections, coronavirus infection, RNA virus infection, lung disease, pneumonia, viral, infections, virus, viral protease inhibitor, protease inhibitor, enzyme inhibitor, severe immunocompromise, anti-viral agents, anti-infectives, ibuzatrelvir, remdesivir, COVID-19
Brief summary
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 at baseline with mild-to-moderate COVID-19.
Detailed description
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
Interventions
DRUGibuzatrelvir
tablet
DRUGremdesivir
injection, for intravenous use
DRUGplacebo for ibuzatrelvir
tablet
DRUGplacebo for remdesivir
injection, for intravenous use
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
This is a double-blind study, with required dedicated unblinded staff for dose preparation for remdesivir and placebo for remdesivir.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older at screening who are non-hospitalized or hospitalized with mild to moderate COVID-19 2. Confirmed SARS-CoV-2 infection as determined by RAT (or other locally approved test) collected within 2 days prior to randomization. Initial onset of symptoms attributable to COVID-19 within 5 days prior to the day of randomization and at least 1 of the specified symptoms attributable to COVID-19 present on the day of randomization. 3. Severely immunocompromised due to: * Solid organ or islet cell transplant recipient who is receiving immunosuppressive therapy; * Active hematologic malignancy (eg, chronic lymphocytic leukemia, non-Hodgkin lymphoma, multiple myeloma, acute leukemia); * Receipt of CAR-T-cell therapy or HCT either within 2 years of transplantation or who are receiving immunosuppressive therapy; * Currently receiving or recently received B-cell depleting therapies (eg, rituximab), where the immunosuppressive effect is still ongoing.
Exclusion criteria
1. Severe or critical COVID-19, or current need for supplemental oxygen. 2. Receiving dialysis or have current kidney failure (ie, eGFR consistently \<15 mL/min) 3. Active liver disease 4. History of hypersensitivity or other contraindication to any of the components of the study interventions, as determined by the investigator 5. Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention. 6. Life expectancy less than 30 days at study entry due to an underlying condition, in the judgement of the investigator. 7. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. 8. Has received any other antiviral for the treatment of the current COVID-19 infection 9. Current use of any prohibited concomitant medication(s) or unwillingness or inability to use a required concomitant medication(s). 10. Current or previous administration of an investigational product (drug or vaccine) within 30 days (or as determined by local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). Authorized or products with conditional approval are not considered investigational. 11. Prior participation in this trial or any clinical trial of ibuzatrelvir. 12. Females who are pregnant, breastfeeding, or who are planning to become pregnant within the timeframe of the study. 13. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 38 days | The difference in the proportion of participants with the composite endpoint of a) Progression to severe COVID-19 or all-cause mortality by Day 38, or b) Evidence of recurrent or persistent SARS-CoV-2 infection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to sustained alleviation of all targeted COVID-19 symptoms | 38 days | 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. |
| Proportion of participants with evidence of recurrent or persistent SARS-CoV-2 infection. | 38 days | The viral load is measured in nasal or nasopharyngeal samples using reverse transcription polymerase chain reaction (RT-PCR) |
| Proportion of participants with COVID-19-related ED visits with medical intervention, COVID-19-related hospitalization, or all-cause mortality. | 38 days | Proportion of participants with COVID-19-related ED visits with medical intervention, COVID-19-related hospitalization, or all-cause mortality. |
| Change from baseline in SARS-CoV-2 RNA level in NP or nasal swabs over time | 38 days | The viral load is measured in nasal or nasopharyngeal samples using reverse transcription polymerase chain reaction (RT-PCR) |
| Proportion of participants with SARS-CoV-2 NP or nasal RNA <LLOQ at each time point | 38 days | Proportion of participants with a SARS-CoV-2 viral load below the lower limit of quantification (LLOQ) of the assay used to measure it. |
| Proportion of participants with viral rebound in SARS-CoV-2 RNA level in NP or nasal swabs | 38 days | 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 to sustained NP or nasal swab SARS-CoV-2 RNA <LLOQ | 38 days | The time it takes for the viral RNA to no longer be detectable in a sample |
| Incidence of Treatment emergent adverse events, serious adverse events, and adverse events leading to discontinuation | 38 days | 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. |
Countries
Argentina, Belgium, Brazil, Denmark, France, Germany, Greece, Japan, Mexico, Netherlands, Puerto Rico, Slovakia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed