Clinical trial NCT05543707: PBI-0451 (Pomotrelvir) Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19
Official title: A Phase 2 Double-blind, Randomized Study to Evaluate the Antiviral Activity, Safety, and Efficacy of Orally Administered PBI-0451(Pomotrelvir) Compared With Placebo in Nonhospitalized Symptomatic Adults With COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID
SARS-CoV-2
Coronavirus
Lead sponsor: Pardes Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2022-09-16
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 2 double-blind, randomized study of PBI-0451(Pomotrelvir) in nonhospitalized symptomatic adults with COVID-19. PBI-0451(Pomotrelvir) is a new chemical entity and inhibitor of the main protease of coronaviruses, including the SARS-CoV-2 that causes COVID-19 disease. This study is designed to evaluate the antiviral activity, safety, and efficacy of orally administered PBI-0451(Pomotrelvir) compared with placebo.

Detailed description: Following randomization on Day 1, subjects will complete baseline assessments prior to receiving their first dose of study drug (PBI-0451 or placebo).

Randomization will be stratified as follows:

* SARS-CoV-2 positive direct test diagnosis ≤ 3 days (target 30%) versus \> 3 days from first onset of COVID-19 symptom(s) ≤ 5 days prior to randomization
* Received primary vaccination series, alone versus any booster shots
* PK substudy participation versus nonparticipation Study drug will be taken with food, approximately 12 hours between doses, at approximately the same time for each BID dose for the remainder of the 5 days of treatment.All subjects will have additional safety and efficacy assessments during the 28-day study period. A follow-up visit (eg, telephone visit, virtual visit, clinic visit, etc. as convenient) will be conducted at Week 24 (± 20 days) after the last dose of study drug for all subjects. Information regarding ongoing or recurrent COVID-19 symptoms, survival status, pregnancy status (for female subjects of childbearing potential and female partners of male subjects), and any hospitalizations or acute/critical care visits (eg, non-admitted hospital or other care facility)that have occurred since the last study visit will be collected. A team of medically qualified individuals, including but not limited to, the Sponsor and the CRO Medical Monitors, and the Drug Safety Consultant are responsible for ongoing review of all AEs, concomitant medications, laboratory values (including virology), and vital signs (including pulse oximetry), worsening of symptoms (COVID-19 symptom questionnaire, including dyspnea), acute/critical care visits (eg, nonadmitted hospital or other care facility), and study drug discontinuations, at a minimum monthly basis throughout the study, per the Safety Monitoring Plan. Subjects who experience severe COVID-19 illness (defined in this study as sustained pulse oximetry \<94%, a respiratory rate of \>30 breaths/min, or dyspnea that requires medical attention) should discontinue study drug and be immediately referred by the Investigator to emergency care or treated by the Investigator for standard of care treatment of symptoms including, but not limited to, other antivirals, supplemental oxygen, corticosteroids, Janus kinase inhibitors, or interleukin-6 blockers, in accordance with the NIH Treatment Guidelines (NIH 2022). The subject should continue participation in the study, with study drug discontinued, for safety follow-up and clinical outcome of the medically attended visit.

Eligibility criteria: Inclusion Criteria:

1. Can understand and sign a written informed consent form (ICF), which must be obtained prior to initiation of any study procedures.
2. Onset of COVID-19 symptoms ≤ 5 days prior to randomization with a positive SARS-CoV-2 test ≤ 24 hours prior to randomization. Authorized NAAT or antigen tests that detect viral RNA or protein, respectively, are allowed.
3. Received primary vaccination series as defined by Centers for Disease Control and Prevention (CDC). Subjects should be advised during informed consent that alternate therapies may be available outside of study participation.
4. ≥ 2 symptoms of acute COVID-19 infection as determined by the investigator from the symptoms listed on the COVID-19 symptoms questionnaire present at randomization
5. Male and nonpregnant, nonlactating female subjects 18 to \< 65 years of age. Females must have a negative serum or urine pregnancy test at screening and prior to the first dose of study drug unless permanently sterile or in a postmenopausal state (see Appendix 3).
6. Male and female subjects and/or their heterosexual partners must either be of nonchildbearing potential or must use effective contraception from screening through 90 days after the last dose of study drug (see Appendix 3)
7. Female subjects must refrain from egg donation and in vitro fertilization during treatment and for ≥ 28 days after the last dose of study drug
8. Male subjects must refrain from sperm donation from screening through 90 days after the last dose of study drug
9. Normal 12-lead electrocardiogram (ECG) evaluation without clinically significant abnormalities
10. Able and willing to comply with all study requirements

Exclusion Criteria:

1. Considered at high-risk of developing severe illness from COVID-19 defined as ≥ 1 CDC underlying medical condition associated with an increased risk of developing severe illness from COVID-19 (see Appendix 5)
2. Unvaccinated against SARS-CoV-2 (defined as having not completed a primary vaccination series)
3. Any SARS-CoV-2 vaccination within 3 month prior to randomization or anticipated to receive a SARS-CoV-2 vaccination (including a booster) during the 28-day study period
4. Currently hospitalized or expected to require hospitalization for COVID-19 within 48 hours of randomization
5. Currently being treated or expected to be treated for COVID-19 with monoclonal antibodies, convalescent serum, or direct-acting antiviral agents (all potential subjects should be informed of evolving treatment options during informed consent that alternate therapies may or may not be available to them outside of study participation)
6. Any clinical condition or laboratory result considered by the investigator to indicate any unstable or poorly controlled underlying clinically significant medical condition(s), active disseminated infection (other than SARS-CoV-2), or other medical condition that could represent a risk to the subject, including increasing the likelihood of a safety event, affect subject compliance, or affect efficacy and/or safety data collected during the 28-day study period
7. Known active liver disease, including nonalcoholic steatohepatitis/nonalcoholic fatty liver disease, chronic or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, primary biliary cirrhosis, Child-Pugh Class B or C, chronic alcoholic liver disease, or acute liver failure
8. Receiving dialysis or having known severe renal impairment (chronic kidney disease, Stage 4 or above)
9. Unable or unwilling to comply with the protocol procedures
10. Participating in another interventional study with an investigational compound or device, including those for COVID-19
11. Known prior participation in this study or another study involving PBI-0451(Pomotrelvir)
12. Females who are pregnant or breastfeeding
13. Oxygen saturation of \< 94% on room air

Primary outcomes:
measure: Virologic Efficacy of PBI-0451 (Pomotrelvir)
timeFrame: Day 3
Secondary outcomes:
measure: Safety and Tolerability of PBI-0451(Pomotrelvir)
timeFrame: Day 1-28
measure: Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 28
timeFrame: Day 1 - 28
measure: Effect of PBI-0451(Pomotrelvir) on SARS-CoV-2
timeFrame: Day 1-28
measure: Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 1-28
timeFrame: Day 1-28
Other outcomes:
measure: Incidence of Rebound SARS-CoV-2 Infection
timeFrame: Day 1-28
Locations:
city: Mesa
country: United States
facility: Voyage Medical
state: Arizona
city: Bakersfield
country: United States
facility: Franco A Felizarta MD
state: California
city: Canoga Park
country: United States
facility: Hope Clinical Research, LLC
state: California
city: Encino
country: United States
facility: Biopharma Informatic, LLC
state: California
city: Fullerton
country: United States
facility: Ascada Research LLC
state: California
city: Long Beach
country: United States
facility: Ark Clinical Research - Long Beach - Clinedge - PPDS
state: California
city: Tarzana
country: United States
facility: Valiance Clinical Research
state: California
city: Westminster
country: United States
facility: Allianz Research Institute - Colorado
state: California
city: Brandon
country: United States
facility: TrueBlue Clinical Research- Brandon - HyperCore - PPDS
state: Florida
city: Cutler Bay
country: United States
facility: Beautiful Minds Clinical Research Center
state: Florida
city: Hialeah
country: United States
facility: Indago Research and Health Center
state: Florida
city: Hialeah
country: United States
facility: Quality Research of South Florida
state: Florida
city: Miami Lakes
country: United States
facility: The Angel Medical Research Corporation
state: Florida
city: Miami Springs
country: United States
facility: South Florida Research
state: Florida
city: Miami
country: United States
facility: Gonzalez M.D. & Aswad M.D. Health Care Services
state: Florida
city: Miami
country: United States
facility: Universal Medical and Research Center, LLC
state: Florida
city: Miami
country: United States
facility: CCM Clinical Research Group
state: Florida
city: Miami
country: United States
facility: D&H National Research Centers
state: Florida
city: Miami
country: United States
facility: Allied Biomedical Research Institute
state: Florida
city: Miami
country: United States
facility: Florida International Medical Research
state: Florida
city: Miami
country: United States
facility: P&S Research, LLC
state: Florida
city: Miramar
country: United States
facility: EMINAT Research
state: Florida
city: Orlando
country: United States
facility: Combined Research Orlando Phase I-IV LLC
state: Florida
city: Ormond Beach
country: United States
facility: Ormond Beach Clinical Research
state: Florida
city: Palm Springs
country: United States
facility: CTMD Research, Inc. - Palm Springs - Hunt - PPDS
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC Inc.
state: Florida
city: Sebastian
country: United States
facility: Infectious Disease Consultants of the Treasure Coast
state: Florida
city: South Miami
country: United States
facility: Westchester General Hospital
state: Florida
city: Tamarac
country: United States
facility: DBC Research
state: Florida
city: Tampa
country: United States
facility: Alliance Clinical Research-(Tampa)
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research - ClinEdge - PPDS
state: Florida
city: Atlanta
country: United States
facility: Agile Clinical Research Trials, LLC
state: Georgia
city: Columbus
country: United States
facility: Centricity Research - Roswell - HyperCore - PPDS
state: Georgia
city: Chicago
country: United States
facility: Eagle Clinical Research
state: Illinois
city: Sterling Heights
country: United States
facility: Revival Research Corporation - Clinedge - PPDS
state: Michigan
city: Clinton
country: United States
facility: Safe Haven Clinical Research
state: Mississippi
city: Butte
country: United States
facility: Mercury Street Medical Group
state: Montana
city: Las Vegas
country: United States
facility: Las Vegas Medical Research
state: Nevada
city: Denver
country: United States
facility: Research Carolina Elite
state: North Carolina
city: Dayton
country: United States
facility: WellNow Urgent Care Troy Urgent Care
state: Ohio
city: Vandalia
country: United States
facility: STAT Research
state: Ohio
city: West Columbia
country: United States
facility: Clinovacare Medical Clinical Research Center
state: South Carolina
city: West Columbia
country: United States
facility: Veritas Health Care Group
state: South Carolina
city: Franklin
country: United States
facility: Clinical Trials Center of Middle Tennessee
state: Tennessee
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: Zenos Clinical Research
state: Texas
city: Edinburg
country: United States
facility: Proactive Clinical Research, LLC Edinburg
state: Texas
city: Forney
country: United States
facility: Care United Research, LLC
state: Texas
city: Houston
country: United States
facility: Mercy Family Clinic
state: Texas
city: Houston
country: United States
facility: Xpress Trials
state: Texas
city: Houston
country: United States
facility: Diversified Medical Practices, P.A.
state: Texas
city: Lewisville
country: United States
facility: Epic Clinical Research
state: Texas
city: San Antonio
country: United States
facility: VIP Trials
state: Texas
city: Suffolk
country: United States
facility: Suffolk Multispecialty Research
state: Virginia
Study officials:
affiliation: Pardes Biosciences
name: David Wilfret, MD
role: STUDY_DIRECTOR
References: