PBI-0451 (Pomotrelvir) Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19

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

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: PBI-0451 (Pomotrelvir); Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85210
      • Voyage Medical
  • California
    • Bakersfield, California, United States, 93301-1692
      • Franco A Felizarta MD
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research, LLC
    • Encino, California, United States, 91436
      • Biopharma Informatic, LLC
    • Fullerton, California, United States, 92835-3424
      • Ascada Research LLC
    • Long Beach, California, United States, 92868
      • Ark Clinical Research - Long Beach - ClinEdge - PPDS
    • Tarzana, California, United States, 91356-6695
      • Valiance Clinical Research
    • Westminster, California, United States, 92683-4454
      • Allianz Research Institute - Colorado
  • Florida
    • Brandon, Florida, United States, 33511-4850
      • TrueBlue Clinical Research- Brandon - HyperCore - PPDS
    • Cutler Bay, Florida, United States, 33157
      • Beautiful Minds Clinical Research Center
    • Hialeah, Florida, United States, 33012-4174
      • Indago Research and Health Center
    • Hialeah, Florida, United States, 33016-1811
      • Quality Research of South Florida
    • Miami, Florida, United States, 33155-4630
      • Allied Biomedical Research Institute
    • Miami, Florida, United States, 33155
      • Florida International Medical Research
    • Miami, Florida, United States, 33175
      • P&S Research, LLC
    • Miami, Florida, United States, 33126
      • Universal Medical and Research Center, LLC
    • Miami, Florida, United States, 33125
      • Gonzalez M.D. & Aswad M.D. Health Care Services
    • Miami, Florida, United States, 33133-4231
      • CCM Clinical Research Group
    • Miami, Florida, United States, 33155-3262
      • D&H National Research Centers
    • Miami Lakes, Florida, United States, 33016-1641
      • The Angel Medical Research Corporation
    • Miami Springs, Florida, United States, 33166
      • South Florida Research
    • Miramar, Florida, United States, 33027
      • EMINAT Research
    • Orlando, Florida, United States, 32803
      • Combined Research Orlando Phase I-IV LLC
    • Ormond Beach, Florida, United States, 32174
      • Ormond Beach Clinical Research
    • Palm Springs, Florida, United States, 33406
      • CTMD Research, Inc. - Palm Springs - Hunt - PPDS
    • Palmetto Bay, Florida, United States, 33157-5503
      • IMIC Inc.
    • Sebastian, Florida, United States, 32958
      • Infectious Disease Consultants of the Treasure Coast
    • South Miami, Florida, United States, 33143-5045
      • Westchester General Hospital
    • Tamarac, Florida, United States, 33321
      • DBC Research
    • Tampa, Florida, United States, 33615-3816
      • Alliance Clinical Research-(Tampa)
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research - ClinEdge - PPDS
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Agile Clinical Research Trials, LLC
    • Columbus, Georgia, United States, 31904
      • Centricity Research - Roswell - HyperCore - PPDS
  • Illinois
    • Chicago, Illinois, United States, 60621-3116
      • Eagle Clinical Research
  • Michigan
    • Sterling Heights, Michigan, United States, 48312
      • Revival Research Corporation - Clinedge - PPDS
  • Mississippi
    • Clinton, Mississippi, United States, 39056-5606
      • Safe Haven Clinical Research
  • Montana
    • Butte, Montana, United States, 59701-1652
      • Mercury Street Medical Group
  • Nevada
    • Las Vegas, Nevada, United States, 89128-0373
      • Las Vegas Medical Research
  • North Carolina
    • Denver, North Carolina, United States, 28037-7929
      • Research Carolina Elite
  • Ohio
    • Dayton, Ohio, United States, 45424
      • WellNow Urgent Care Troy Urgent Care
    • Vandalia, Ohio, United States, 45377
      • STAT Research
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Clinovacare Medical Clinical Research Center
    • West Columbia, South Carolina, United States, 29169
      • Veritas Health Care Group
  • Tennessee
    • Franklin, Tennessee, United States, 37067-5663
      • Clinical Trials Center of Middle Tennessee
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75230-6895
      • Zenos Clinical Research
    • Edinburg, Texas, United States, 78539-4660
      • Proactive Clinical Research, LLC Edinburg
    • Forney, Texas, United States, 75126-4174
      • Care United Research, LLC
    • Houston, Texas, United States, 75211
      • Mercy Family Clinic
    • Houston, Texas, United States, 77036-8280
      • Xpress Trials
    • Houston, Texas, United States, 77084
      • Diversified Medical Practices, P.A.
    • Lewisville, Texas, United States, 75057
      • Epic Clinical Research
    • San Antonio, Texas, United States, 78230
      • VIP Trials
  • Virginia
    • Suffolk, Virginia, United States, 23435-3762
      • Suffolk Multispecialty Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PBI-0451 (Pomotrelvir); PBI-0451(Pomotrelvir): 2 x 350 mg tablets administered orally twice daily (BID) (1400 mg/day) with food for 5 days (10 total doses)	Drug: PBI-0451 (Pomotrelvir); 2 × 350 mg tablets administered orally twice daily (BID) (1400 mg/day) with food for 5 days (10 total doses); Other Names: Active
Placebo Comparator: Placebo; PBI-0451(Pomotrelvir): 2 x placebo to match PBI-0451(Pomotrelvir) tablets administered orally twice daily (BID) with food for 5 days (10 total doses)	Drug: Placebo; 2 × placebo to match PBI-0451(Pomotrelvir) tablets administered orally BID with food for 5 days (10 total doses)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virologic Efficacy of PBI-0451 (Pomotrelvir)	The primary efficacy endpoint was the proportion of participants below LOD for infectious SARS-CoV-2 on Day 3 by IVA from MT nasal swabs for the mITTV analysis set.	Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of PBI-0451(Pomotrelvir)	Number of treatment-emergent adverse events (AEs), serious adverse events (SAEs), discontinuations due to AEs, and Grade 3 or 4 laboratory abnormalities	Day 1-28
Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 28	Number of Pomotrelvir treated participants with sustained symptom resolution through Day 28 versus untreated Placebo participants	Day 1 - 28
Effect of PBI-0451(Pomotrelvir) on SARS-CoV-2	Presence of SARS-CoV-2 virus, viral RNA or viral antigen based on IVA, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and rapid antigen test (RAT), as specified in the Clinical Virology Analysis Plan (CVAP)	Day 1-28
Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 1-28	The median number of days to sustained resolution of of all 14 COVID-19 symptoms for the PBI-0451 vs Placebo groups through Day 28.	Day 1-28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Rebound SARS-CoV-2 Infection	Percentage of participantss with clinical and/or virologic rebound	Day 1-28

Collaborators and Investigators

• Sponsor: Pardes Biosciences, Inc.
• Investigators: Study Director: David Wilfret, MD, Pardes Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2022
• Primary Completion (Actual): January 27, 2023
• Study Completion (Actual): April 14, 2023

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: November 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; COVID
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: PBI-0451-0002; 2022-001195-33 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No