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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05543707
• Other study ID #: PBI-0451-0002
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 21, 2022
• Est. completion date: July 2, 2023

Study information

• Verified date: March 2023
• Source: Pardes Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 210
• Est. completion date: July 2, 2023
• Est. primary completion date: June 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• PBI-0451 (Pomotrelvir)
2 × 350 mg tablets administered orally twice daily (BID) (1400 mg/day) with food for 5 days (10 total doses)
• Placebo
2 × placebo to match PBI-0451(Pomotrelvir) tablets administered orally BID with food for 5 days (10 total doses)

Locations

Country	Name	City	State
United States	Agile Clinical Research Trials, LLC	Atlanta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	Franco A Felizarta MD	Bakersfield	California
United States	TrueBlue Clinical Research- Brandon - HyperCore - PPDS	Brandon	Florida
United States	Mercury Street Medical Group	Butte	Montana
United States	Hope Clinical Research, LLC	Canoga Park	California
United States	Eagle Clinical Research	Chicago	Illinois
United States	Safe Haven Clinical Research	Clinton	Mississippi
United States	Centricity Research - Roswell - HyperCore - PPDS	Columbus	Georgia
United States	Beautiful Minds Clinical Research Center	Cutler Bay	Florida
United States	Zenos Clinical Research	Dallas	Texas
United States	WellNow Urgent Care Troy Urgent Care	Dayton	Ohio
United States	Research Carolina Elite	Denver	North Carolina
United States	Proactive Clinical Research, LLC Edinburg	Edinburg	Texas
United States	Biopharma Informatic, LLC	Encino	California
United States	Care United Research, LLC	Forney	Texas
United States	Clinical Trials Center of Middle Tennessee	Franklin	Tennessee
United States	Ascada Research LLC	Fullerton	California
United States	Indago Research and Health Center	Hialeah	Florida
United States	Quality Research of South Florida	Hialeah	Florida
United States	Diversified Medical Practices, P.A.	Houston	Texas
United States	Mercy Family Clinic	Houston	Texas
United States	Xpress Trials	Houston	Texas
United States	Las Vegas Medical Research	Las Vegas	Nevada
United States	Epic Clinical Research	Lewisville	Texas
United States	Ark Clinical Research - Long Beach - Clinedge - PPDS	Long Beach	California
United States	Voyage Medical	Mesa	Arizona
United States	Allied Biomedical Research Institute	Miami	Florida
United States	CCM Clinical Research Group	Miami	Florida
United States	D&H National Research Centers	Miami	Florida
United States	Florida International Medical Research	Miami	Florida
United States	Gonzalez M.D. & Aswad M.D. Health Care Services	Miami	Florida
United States	P&S Research, LLC	Miami	Florida
United States	Universal Medical and Research Center, LLC	Miami	Florida
United States	The Angel Medical Research Corporation	Miami Lakes	Florida
United States	South Florida Research	Miami Springs	Florida
United States	EMINAT Research	Miramar	Florida
United States	Combined Research Orlando Phase I-IV LLC	Orlando	Florida
United States	Ormond Beach Clinical Research	Ormond Beach	Florida
United States	CTMD Research, Inc. - Palm Springs - Hunt - PPDS	Palm Springs	Florida
United States	IMIC Inc.	Palmetto Bay	Florida
United States	VIP Trials	San Antonio	Texas
United States	Infectious Disease Consultants of the Treasure Coast	Sebastian	Florida
United States	Westchester General Hospital	South Miami	Florida
United States	Revival Research Corporation - Clinedge - PPDS	Sterling Heights	Michigan
United States	Suffolk Multispecialty Research	Suffolk	Virginia
United States	DBC Research	Tamarac	Florida
United States	Alliance Clinical Research-(Tampa)	Tampa	Florida
United States	Valiance Clinical Research	Tarzana	California
United States	STAT Research	Vandalia	Ohio
United States	Clinovacare Medical Clinical Research Center	West Columbia	South Carolina
United States	Veritas Health Care Group	West Columbia	South Carolina
United States	Palm Beach Research - ClinEdge - PPDS	West Palm Beach	Florida
United States	Allianz Research Institute - Colorado	Westminster	California

Sponsors (1)

Lead Sponsor	Collaborator
Pardes Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To evaluate SARS-CoV-2 resistance to PBI-0451(Pomotrelvir)	Sequence analysis of the SARS-CoV-2 main protease (Mpro) gene (nsp5) and Mpro cleavage sites	Day 1-28
Other	To evaluate SARS-CoV-2 resistant variant susceptibility to PBI-0451(Pomotrelvir)	Susceptibility analysis of SARS-CoV-2 variants with Mpro amino acid substitutions and variants with substitutions in Mpro cleavage sites in the SARS-CoV-2 polyprotein	Day 1-28
Other	To evaluate the relationship between SARS-CoV-2 detection methods	Correlation of SARS-CoV-2 detection by IVA, RAT, and qRT-PCR, as specified in the CVAP	Day 1-28
Other	To evaluate the incidence of rebound SARS-CoV-2 infection	Proportion of subjects with clinical and/or virologic rebound	Day 1-28
Other	To evaluate plasma concentrations of a dose of PBI-0451(Pomotrelvir) to determine AUC from an intensive PK substudy of up to 50 subjects	Area under the plasma concentration-time profile from Time zero (predose) to end of dosing interval (up to 12 hours postdose)	Any study visit Day 1-5
Other	To evaluate plasma concentrations of a dose of PBI-0451(Pomotrelvir) to determine Cmax from an intensive PK substudy of up to 50 subjects	Maximum concentration is estimated based on the plasma concentrations from Time zero (predose) to end of dosing interval (up to 12 hours postdose)	Any study visit Day 1-5
Other	To evaluate plasma concentrations of a dose of PBI-0451(Pomotrelvir) to determine Tmax from an intensive PK substudy of up to 50 subjects	Tmax is the time to maximum concentration from Time zero (predose) to end of dosing interval (up to 12 hours postdose)	Any study visit Day 1-5
Primary	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	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
Secondary	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
Secondary	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