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A PHASE 2/3, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PLACEBO CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF 2 REGIMENS OF ORALLY ADMINISTERED PF-07321332/RITONAVIR IN PREVENTING SYMPTOMATIC SARS-COV-2 INFECTION IN ADULT HOUSEHOLD CONTACTS OF AN INDIVIDUAL WITH SYMPTOMATIC COVID-19

A Study of a Potential Oral Treatment to Prevent COVID-19 in Adults Who Are Exposed to Household Member(s) With a Confirmed Symptomatic COVID-19 Infection

2957

Baseline characteristics, including risk factors for progression to severe coronavirus disease 2019 (COVID-19) were balanced across treatment groups: *The mean (standard deviation) age of participants was 43.06 (14.77) years with similar proportion of Males (46.8%) and Females (53.2%). *At Baseline, most participants (94.7%) had a negative reverse transcription polymerase chain reaction (RT-PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result. *At Baseline, most participants had a positive serology antibody test (90.7%).

Based on the exclusion of 2 sites from the reanalysis, the number of participants analyzed per analysis set was: Full Analysis Set, 2736; Safety Analysis Set, 2721; modified Intent-to-Treat (mITT), 2514; mITT1, 115; mITT2, 1838. The total of 157 participants (5.7%) discontinued the study treatment for the following reasons (n, %); adverse events (AEs) (35, 1.3%); noncompliance with study drug (1, <0.1%); pregnancy (1, <0.1%), withdrawal by participant (61, 2.2%); medication error without associated AE (26, 1.0%); no longer meets eligibility criteria (6, 0.2%); and other (27, 1.0%).

The overall incidence of all-causality treatment-emergent adverse events was generally similar across the treatment groups. These AEs were mostly mild (Grade 1) or moderate (Grade 2) in severity, except for 1 severe (Grade 3) event of dysgeusia and 1 severe (Grade 3) event Fibrin D dimer increased in the 5-day regimen and 1 severe (Grade 3) event of dysgeusia in the 10-day regimen. There were no deaths related to an AE in any treatment group. There were no discontinuations from the study due to AEs. The proportion of participants with all-causality serious adverse events (SAEs) was low and similar across treatment groups. All of the SAEs were severe (Grade 3) except for COVID-19 Pneumonia in the 10-day regimen which was potentially life-threatening (Grade 4). None of these SAEs were considered related to the study intervention. The proportion of participants in the nirmatrelvir/ritonavir 5-day and 10-day regimens (1.1% and 1.2%, respectively) and in placebo (1.6%) who discontinued study intervention due to an AE and continued in the study, was low and generally similar. Few (<=0.5%) events leading to discontinuation of study intervention in any treatment group were considered by the investigator to be related to study intervention.

Primary Endpoint Results The study was powered to detect a 70% risk reduction of developing symptomatic, RT-PCR or rapid antigen test (RAT) confirmed SARS-CoV-2 infection through Day 14 relative to placebo. Among participants who had a negative RT-PCR result at baseline (ie, mITT), the proportion of participants who developed symptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection through Day 14 was 2.6% (n = 22) for the nirmatrelvir/ritonavir 5-day regimen, 2.4% (n = 20) for the nirmatrelvir/ritonavir 10-day regimen, both lower than the 3.9% (n = 33) for placebo. The risk reduction vs placebo was 29.8% (p = 0.1722) and 35.5% (p = 0.1163) for the 5-day and 10-day regimens, respectively. Primary Endpoint by Subgroup Results Results of subgroup analyses by participant age, sex, race, geographic region, and pre- or post-emergence of the omicron variant were generally consistent with the primary analysis except for presence of risk factors and baseline serology antibody status. In participants with or without risk factors for severe COVID-19 illness, a numerically greater risk reduction of developing symptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection through Day 14 was observed for nirmatrelvir/ritonavir 5-day (64%) and 10-day (65%) regimens vs placebo for participants who did not have risk factors for severe COVID-19 than for participants who had risk factors. In participants with or without antibodies to SARS-CoV-2 at baseline, a numerically greater risk reduction of developing symptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection through Day 14 was observed in participants for the 5-day (41%) and 10-day (43%) regimens vs placebo who were sero-positive at baseline than in participants who were sero-negative at baseline. Key Secondary Endpoint Results Among participants who had a negative RT-PCR result at baseline and were at increased risk of severe COVID-19 illness (ie, mITT2), the proportion of participants with symptomatic SARS-CoV-2 infection through Day 14 was 2.9% (n = 18) and 2.6% (n = 16) for the nirmatrelvir/ritonavir 5-day and 10-day regimens, respectively, and 3.5% (n = 21) in placebo. The risk reduction vs placebo was 12.0% (p = 0.6766) and 19.1% (p = 0.5070) for the 5-day and 10-day regimens, respectively.

The 5-day and 10-day regimens of nirmatrelvir/ritonavir vs placebo showed a risk reduction of 29.8% and 35.5%, respectively, for symptomatic RT-PCR or RAT confirmed SARS-CoV-2 infection through Day 14 in participants who had a negative RT-PCR result at baseline and were household contacts of an individual with symptomatic COVID-19. The 5-day and 10-day regimens of nirmatrelvir/ritonavir was safe and well-tolerated.

Oct. 13, 2023

May. 06, 2023

https://classic.clinicaltrials.gov/ct2/show/study/NCT05047601

Yes

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210349

Kawai Norisuke

Pfizer R&D Japan G.K.

Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo

clinical-trials@pfizer.com

Clinical Trials Information Desk

Pfizer R&D Japan G.K.

Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo

+81-3-5309-7000

clinical-trials@pfizer.com

Complete

Oct. 02, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

prevention purpose

*Participants who have a negative screening SARS-CoV-2 rapid antigen test result and who are asymptomatic household contacts to an individual who is symptomatic and tested positive for SARS CoV-2 within 96 hours of randomization of the participant.
*Fertile participants must agree to use a highly effective method of contraception

*History of SARS-CoV-2 infection in the past 6 months
*Experiencing measured fever (>38 degrees) or other signs or symptoms consistent with COVID-19
*Known medical history of active liver disease
*Chronic Kidney Disease or have known moderate to severe renal impairment
*Known human immunodeficiency virus (HIV) infection with a viral load greater than 400 copies/mL within the last 6 months or taking prohibited medications for HIV treatment
*Suspected or confirmed concurrent active systemic infection
*Active cancer requiring treatment with prohibited medication
*Current or expected use of any medications or substances that are highly dependent on CYP3A4 for clearance or are strong inducers of CYP3A4
*Has received approved, authorized, or investigational anti-SARS-CoV-2 mAb, convalescent plasma, other drugs for treatment of COVID-19, or other anti-SARS-CoV-2 biologic products within 6 months of screening
*Has received any SARS-CoV-2 vaccine within 6 months prior to screening or is expected to receive a SARS-CoV-2 vaccine or other approved, authorized, or investigational postexposure prophylaxis treatments through Day 38
*Participating in another interventional clinical study with an investigational compound or device, including those for COVID-19
*Known or prior participation in this trial or another trial involving PF-07321332
*Females who are pregnant or breastfeeding

Both

COVID-19

Participants will receive study drug every 12 hours in one of the following regimen:
PF-07321332/ritonavir from Day 1 to Day 5, followed by placebo from Day 6 to Day 10
or
PF-07321332/ritonavir from Day 1 to Day 10
or
Placebo for 10 days from Day 1 to Day 10

Proportion of participants who have a negative reverse transcription polymerase chain reaction (RT-PCR) result at baseline who develop a symptomatic, RT-PCR or rapid antigen test confirmed SARS-CoV-2 infection. [ Time Frame: Day 1 through Day 14 ]

*Percentage of participants who experience adverse events from Day 1 through Day 38.

Of the participants who have a negative RT-PCR result at baseline and who are at increased risk of severe COVID-19 illness:
*Proportion of participants with symptomatic, RT-PCR or Rapid Antigen Test confirmed SARS-CoV-2 infection from Day 1 through Day 14.
*Proportion of participants with COVID-19 related hospitalization or death from any cause by Day 28.

In participants by RT-PCR status at enrolment:
*Proportion of participants with symptomatic or asymptomatic RT-PCR or Rapid Antigen Test confirmed SARS-CoV-2 infection from Day 1 through Day 14.

Of the participants who have a negative RT-PCR result at baseline:
*Time to RT-PCR confirmed SARS-CoV-2 infection from Day 1 through Day 14
*Compare the duration of COVID-19 related signs and symptoms from Day 1 through Day 28.
*Compare the severity of COVID-19 related signs and symptoms from Day 1 through Day 28.
*Pharmacokinetics of PF-07321332 (Day 1 post dose and Day 5 pre dose).
*All cause mortality in participants from Day 1 through Day 38.
*Viral titers measured via RT-PCR in nasal swabs from Day 1 through Day 14.
*Number of days of hospital and ICU stay in participants with COVID-19 related hospitalization from Day 1 through Day 28.
*Number of COVID-19 related medical visits from Day 1 through Day 28.

Sept. 03, 2021

United States/Brazil/South Africa/Puerto Rico/Spain/Hungary/Ukraine/Poland/Bulgaria/Turkey/Mexico/Argentina/Columbia/Taiwan/Republic of Korea/ Malaysia/Czech Republic/Russian Federation/Thailand