A Study to Learn About a Study Medicine Called Ibuzatrelvir in Adult and Adolescent Patients With COVID-19 Who Are Not Hospitalized But Are at Risk For Severe Disease

Phase 3RecruitingNCT06679140

Pfizer2,330 enrolled

Overview

The purpose of the study is to evaluate whether ibuzatrelvir is effective and safe in adults and adolescents with COVID-19 who do not need to be in the hospital but who are at high risk for progression to severe disease. Eligible participants will be randomly assigned (by chance) to receive ibuzatrelvir or matching placebo orally for 5 days. Co-administration of locally available standard of care is allowed. The total duration of the study is around 6 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

2,330

Conditions

COVID-19 SARS-CoV-2 Infection

Interventions

ibuzatrelvir

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 12 to \<18 years of age, weighing at least 40 kg, or ≥18 years of age of any weight at screening. 2. Presence of risk factors for progression to severe COVID-19 at the time of screening based on age: 1. 12 to 49 years of age with at least two risk factors, where one must be moderate immunocompromise; 2. 50 to 64 years of age with at least two risk factors; 3. 65 to 74 years of age with at least one risk factor; 4. For participants 75 years of age or older, there are no requirements related to risk factors. The list of risk factors includes: BMI ≥35 kg/m2; Current smoker; Chronic lung disease; Cardiovascular disease; Type 1 or Type 2 diabetes mellitus; Mild to moderate renal impairment; Neurodevelopmental disorders; Sickle cell disease; Moderate immunosuppression. 3. Confirmed SARS-CoV-2 infection as determined by RAT in nasal or NP specimen collected within 1 day prior to randomization. Initial onset of symptoms attributable to COVID-19 within 5 days prior to randomization and at least 1 of the specified symptoms attributable to COVID-19 present on the day of randomization. Randomization must occur no later than the 5th day, where the onset of symptoms is the first day. 4. Participants must be unable or unwilling to take nirmatrelvir/ritonavir. Exclusion Criteria: 1. Current need or anticipated need for hospitalization within 24 hours, due to signs of severe COVID-19 illness (eg, SpO2 \<94% on room air, respiratory rate \>30 breaths/minute, or lung infiltrates \>50%) or due to other medical conditions requiring hospitalization in the opinion of the site investigator. 2. Receiving dialysis or have known severe renal impairment \[ie, eGFR consistently \<30 mL/min/1.73 m2 for adults or CrCl \<30 mL/min for adolescents\], using the serum creatinine-based CKD-EPI formula or the Cockroft Gault, respectively. 3. Active liver disease with AST or ALT \>3 ULN, Total bilirubin ≥2 × ULN (for Gilbert's syndrome, direct bilirubin \>ULN is exclusionary) within the past 3 months, or liver function impairment with Class C per Child Pugh classification. 4. Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention. 5. Ongoing Long COVID or Post Acute Sequelae of COVID-19 diagnosis. 6. Severely immunocompromised. 7. Any comorbidity requiring hospitalization and/or surgery within 7 days prior to study entry, or that is considered life threatening within 30 days prior to study entry, as determined by the investigator. 8. History of hypersensitivity or other contraindication to any of the components of the study interventions. 9. 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. 10. Current use of any prohibited concomitant medication(s). 10.Has received any other antiviral for the treatment of COVID-19, including remdesivir, nirmatrelvir/ritonavir, molnupiravir, or COVID-19 mAbs within 30 days or 5 half-lives \[whichever is longer\] prior to screening, or received convalescent COVID-19 plasma within 12 months. 12.Received any dose of a COVID-19 vaccine within 4 months of randomization or expected to receive one through Day 34. 13.Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). 14.Prior participation in this clinical trial or any other clinical trial of ibuzatrelvir. 15.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.

Outcomes

Primary Outcomes

Proportion of participants with COVID-19 related emergency department visits, all cause hospitalization and all cause mortality

The difference in proportions of patients requiring COVID 19 related emergency department visits with administration of supplemental oxygen, COVID-19 antiviral or IV treatment (eg hydration, antibiotics, or corticosteroids), all-cause hospitalization, or all-cause death through Day 28 between ibuzatrelvir and placebo, among patients who were treated ≤5 days after COVID-19 symptom onset and who were not receiving background SoC treatment for their COVID-19 infection at baseline.

Time frame: Day 1 through Day 28

Secondary Outcomes

Time to sustained resolution of all COVID-19 targeted symptoms

The difference in median time to sustained resolution 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: Day 1 to Day 28

Proportion of participants with post acute COVID-19 medical events

Medical events include cardiovascular events, pulmonary events, acute kidney disease and thromboembolic events.

Time frame: Day 29 to Week 24

Proportion of participants with cardiovascular, renal and pulmonary events

Medical events include cardiovascular events, pulmonary events, acute kidney disease and thromboembolic events.

Time frame: Day 1 to Week 24

Proportion of participants with Long COVID symptoms

The difference in proportions of patients with Long COVID symptoms at Week 24. Symptoms will be assessed through a weekly electronic diary.

Time frame: Day 29 to Week 24

Changes from baseline in SARS-CoV-2 RNA levels in nasopharyngeal/nasal swabs

The viral load is measured in nasal or nasopharyngeal samples using reverse transcription polymerase chain reaction (RT-PCR)

Time frame: Day 1 through Day 34

Time to SARS-CoV-2 RNA <LLOQ

Time needed to achieve a viral load below the lower limit of quantification of the essay used to measure it.

Time frame: Day 1 through Day 34

Proportion of participants with SARS-CoV-2 RNA <LLOQ at each visit

Proportion of participants with a SARS-CoV-2 viral load below the lower limit of quantification of the essay used to measure it.

Time frame: Day 1 through Day 34

Proportion of participants with rebound in SARS-CoV-2 RNA levels in nasopharyngeal swab

Virologic rebound is defined as: at any follow up visit, a viral RNA level increase from End of Treatment (Day 5) of ≥ 1.0 log10 copies/mL resulting in a viral RNA level ≥3.0 log10 copies/mL.

Time frame: Day 10 and Day 14

Proportion of participants with virologic and symptomatic rebound through Day 28

symptoms rebound is defined as: after achieving short symptom recovery (the first day of at least two consecutive diary entries where all targeted symptoms are absent), symptom rebound is the first day of at least two consecutive diary entries after Day 5 where there is any targeted symptom (regardless of severity), or when a participant is hospitalized after symptom recovery.

Time frame: Day 10 to Day 34

Proportion of participants with COVID-19-related hospitalization or all cause death through Day 28.

Time frame: Day 1 to Day 28

Number of days in hospital and ICU stay in participants with hospitalization (all-cause).

Time frame: Day 1 to Week 24

Number of medical visits through Week 24.

medical visits include emergency department visits, hospitalizations, visits to the general practitioner and specialist.

Time frame: Day 1 to Week 24

Proportion of participants with hospitalization (all-cause) or death (all-cause) through Week 24.

Time frame: Day 1 to Week 24

Time (days) to sustained alleviation of all targeted symptoms through Day 28.

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: Day 1 to Day 28

Proportion of participants with severe symptoms attributed to COVID-19 through Day 28.

Participants are required to record the severity of their Covid-19 symptoms over the past 24 hours daily on a 4-point scale ranging from 0 to 3, higher scores indicated more severity. The scale was reported as 0= no symptoms, 1=mild, 2=moderate and 3=severe. A participant with severe score for any targeted symptoms post-baseline is counted as severe. Percentage of participants with severe Covid-19 signs and symptoms is reported.

Time frame: Day 1 to Day 28

Duration of each targeted COVID-19 symptom.

Duration of each targeted COVID-19 symptom is defined as (First Date when the symptom achieved sustained alleviation/resolved)-(First Dose Date) + I for each participant with baseline severity of mild, moderate, or severe.

Time frame: Day 1 to Day 28

Proportion of participants with symptomatic rebound through Day 28.

Definition of symptomatic rebound: After achieving short symptom recovery (the first day of at least two consecutive diary entries where all targeted symptoms are absent), symptom rebound is the first day of at least two consecutive diary entries after Day 5 where there is any targeted symptom (regardless of severity), or when a participant is hospitalized after symptom recovery

Time frame: Day 1 to Day 28

Incidence of treatment emergent adverse events

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: Day 1 to Day 34

Incidence of SAEs and AEs leading to discontinuations.

Time frame: Day 1 to Day 34

A Study to Learn About a Study Medicine Called Ibuzatrelvir in Adult and Adolescent Patients With COVID-19 Who Are Not Hospitalized But Are at Risk For Severe Disease

Overview

Conditions

Interventions

Eligibility

Locations (231)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts