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

Study Overview
=================
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.

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

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Drug: PBI-0451 (Pomotrelvir)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Can understand and sign a written informed consent form (ICF), which must be obtained prior to initiation of any study procedures. 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. 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. ≥ 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 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). 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) Female subjects must refrain from egg donation and in vitro fertilization during treatment and for ≥ 28 days after the last dose of study drug Male subjects must refrain from sperm donation from screening through 90 days after the last dose of study drug Normal 12-lead electrocardiogram (ECG) evaluation without clinically significant abnormalities Able and willing to comply with all study requirements Exclusion Criteria: 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) Unvaccinated against SARS-CoV-2 (defined as having not completed a primary vaccination series) 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 Currently hospitalized or expected to require hospitalization for COVID-19 within 48 hours of randomization 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) 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 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 Receiving dialysis or having known severe renal impairment (chronic kidney disease, Stage 4 or above) Unable or unwilling to comply with the protocol procedures Participating in another interventional study with an investigational compound or device, including those for COVID-19 Known prior participation in this study or another study involving PBI-0451(Pomotrelvir) Females who are pregnant or breastfeeding Oxygen saturation of < 94% on room air

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the antiviral activity of PBI-0451 (Pomotrelvir) | Proportion of subjects below the limit of detection (LOD) for infectious SARS-CoV-2 on Day 3 of treatment by infectious virus assay (IVA) from mid-turbinate (MT) swabs | Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate 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 | 
| To evaluate clinical efficacy of PBI-0451(Pomotrelvir) versus placebo through study Day 28 | Proportion of subjects with sustained symptom resolution through Day 28; time to sustained symptom resolution through Day 28; proportion of subjects with COVID-19 related hospitalization or death from any cause through Day 28; severity of targeted COVID-19 symptoms; number of COVID-19 related medical visits other than hospitalization, including acute/critical care visits through Day 28; number of days in any hospital unit for treatment of COVID-19 | Day 1-28 | 
| To evaluate the 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID, SARS-CoV-2, Coronavirus