New Phase 2 clinical trial testing the effect of Pfizer's PF-07817883 (Mpro inhibitor, oral) on SARS-CoV-2 RNA levels in non-hospitalized, symptomatic COVID-19 adult patients

Pfizer registered a new Phase 2 clinical trial testing the effect of PF-07817883 (SARS-CoV-2 3CL protease inhibitor, oral COVID-19 treatment) on SARS-CoV-2 RNA levels in non-hospitalized, symptomatic COVID-19 adult patients. 

Key Details:

NCT05799495 – Clinical Trial Information 

• Estimated timing: Start date is Apr 21, 2023 and primary completion /study completion date is Dec 13, 2023 
• Estimated Enrollment: 228  
• Target Follow Up Duration: 4 week follow up 
• Dosing: 100mg, 300mg, 600mg will be administer BID for 5 days in 3 different arms along with a 4^th placebo arm
• Primary Outcome Measures: Change from baseline to day 5 in SARS-CoV-2 RNA levels 
• Secondary Outcome Measures: Change from baseline SARS-CoV-2 RNA levels on days 3, 10, and 14; incidence of treatment related AEs and SAEs; significant abnormal lab values/vital signs/ECGs; treatment related study discontinuations 
• Trial Locations: (none listed at this time)
• Key Inclusion Criteria: Adults with symptomatic COVID-19 and a confirmed SARS-CoV-2 infection within 48 hours of randomization 
• Key Exclusion Criteria: Need for hospitalization at, or up to, 24 hours after randomization; immunocompromised patients (see trial posting for criteria), oxygen saturation <92%; on or expected to receive another antiviral for COVID-19 treatment 
  • There is no specification of risk factors in this protocol, suggesting it may allow for the enrollment of both high and standard-risk non-hospitalized COVID-19 patients

Impact assessment:

• Aside from PAXLOVID, PF-07817883 may be the strongest direct competitor for COVID treatments because of its similar lack of DDI risks (this is reinforced by the lack of exclusion criteria for patients taking medications or substances that are highly dependent on CYP3A4 for clearance or are strong inducers of CYP3A4) and it being developed by a well-resourced manufacturer in Pfizer that is committed to COVID-19 treatments.
• It is unclear whether Pfizer plans to eventually replace PAXLOVID with PF-07817883 or have them target different patients populations for each (e.g., reserve PF-07817883 for patients with significant DDI risks). This may depend on the level of efficacy PF-07817883 in its anticipated Phase 3 study.
• timing and indications for launch may differ based on data in high or standard-risk patients and which of these patient populations Pfizer targets for the anticipated Phase 3 study on PF-07817883.
• Testing multiple doses of PF-07817883 may improve the probability of trial success for this Phase 2 given our hypothesis that Pardes’s non-ritonavir-boosted Mpro inhibitor, pomotrelvir, may have missed its Phase 2 primary endpoint due to being underdosed.