Pfizer has commenced a Phase 3 clinical trial to evaluate the safety and efficacy of ibuzatrelvir, a novel oral antiviral treatment for COVID-19. The study is designed to determine the effectiveness of ibuzatrelvir in treating high-risk, non-hospitalized patients who are at risk of progressing to severe disease.
The Phase 3 trial, titled “An Interventional Efficacy and Safety, Phase 3, Double-Blind, 2-Arm Study to Investigate Orally Administered Ibuzatrelvir Compared with Placebo in Non-Hospitalized Symptomatic Adult and Adolescent Participants with COVID-19 Who Are at High Risk of Progressing to Severe Illness” (ClinicalTrials.gov ID NCT06679140), seeks to provide critical data on ibuzatrelvir's potential as an alternative to existing COVID-19 treatments.
Addressing Limitations of Current Treatments
Unlike PAXLOVID (nirmatrelvir-ritonavir), the current standard treatment, ibuzatrelvir is designed to be administered as a single agent. This approach aims to mitigate the risk of drug-drug interactions associated with ritonavir and eliminate the taste disturbances reported by some patients taking PAXLOVID. According to Charlotte Allerton, Head of Discovery & Early Development at Pfizer, ibuzatrelvir may also reduce interactions with drugs metabolized by CYP3A4 enzymes, based on pharmacokinetic study data.
Study Design and Objectives
The Phase 3 trial will enroll adults and adolescents diagnosed with COVID-19 who are not hospitalized. Participants will be randomly assigned to receive either ibuzatrelvir or a placebo for five days. The primary endpoint of the study is to assess the proportion of participants who experience COVID-19-related emergency department visits, hospitalization, or death within 28 days. Secondary endpoints include symptom resolution time, viral load reduction, and the incidence of Long COVID symptoms.
Allerton noted, "This is a Phase 3, superiority, adaptive, randomized, double-blind, placebo-controlled, multicenter study. It will assess the efficacy, safety, and tolerability of ibuzatrelvir in non-hospitalized, symptomatic adult and adolescent participants who are at high risk of progressing to severe illness."
The trial aims to enroll approximately 2,330 eligible participants with a confirmed SARS-CoV-2 diagnosis within one day prior to randomization and symptom onset within five days. Participants will be randomized 1:1 to receive either ibuzatrelvir or placebo twice daily for five days.
Following the five-day treatment phase, participants will be monitored for safety and efficacy endpoints for up to 24 weeks. The primary outcome measure will be the proportion of participants with COVID-19-related emergency department visits, all-cause hospitalization, and all-cause mortality.
Simplified Treatment Option
Ibuzatrelvir is a second-generation antiviral that targets SARS-CoV-2. By eliminating the need for ritonavir co-administration, ibuzatrelvir could simplify the treatment regimen, particularly for patients who require extended antiviral treatment or who are sensitive to drug interactions.
Throughout the trial, participants will be monitored for key health outcomes, including symptom resolution, viral load reduction, and adverse events related to the treatment. Secondary endpoints will track the incidence of cardiovascular, renal, and pulmonary complications, as well as signs of Long COVID up to 24 weeks after treatment.
Addressing Future Challenges in COVID-19 Treatment
As COVID-19 continues to evolve, having a range of effective treatment options remains critical. While PAXLOVID remains the primary antiviral treatment for high-risk patients, new therapies like ibuzatrelvir are necessary to meet patients' evolving needs, especially as new variants emerge.
Allerton explained, "Current variants of concern arise due to mutations in the spike protein of the SARS-CoV-2 virus. However, like PAXLOVID, ibuzatrelvir works intracellularly by inhibiting the highly conserved Mpro protease of the SARS-CoV-2 virus to block viral replication. This mechanism suggests that ibuzatrelvir, like PAXLOVID, will remain effective against current variants of concern."
The Phase 3 trial of ibuzatrelvir is expected to provide valuable insights into how this new treatment compares to existing options in reducing disease severity, preventing hospitalization, and improving patient outcomes. The results from this trial will help shape strategies for managing COVID-19.
