COVID-19
Conditions
Keywords
COVID, SARS-CoV-2, Coronavirus
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.
Interventions
DRUGPBI-0451 (Pomotrelvir)
2 × 350 mg tablets administered orally twice daily (BID) (1400 mg/day) with food for 5 days (10 total doses)
DRUGPlacebo
2 × placebo to match PBI-0451(Pomotrelvir) tablets administered orally BID with food for 5 days (10 total doses)
Sponsors
Pardes Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Virologic Efficacy of PBI-0451 (Pomotrelvir) | Day 3 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of PBI-0451(Pomotrelvir) | Day 1-28 | Number of treatment-emergent adverse events (AEs), serious adverse events (SAEs), discontinuations due to AEs, and Grade 3 or 4 laboratory abnormalities |
| Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 28 | Day 1 - 28 | Number of Pomotrelvir treated participants with sustained symptom resolution through Day 28 versus untreated Placebo participants |
| Effect of PBI-0451(Pomotrelvir) on SARS-CoV-2 | Day 1-28 | 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) |
| Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 1-28 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Rebound SARS-CoV-2 Infection | Day 1-28 | Percentage of participantss with clinical and/or virologic rebound |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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)
PBI-0451 (Pomotrelvir): 2 × 350 mg tablets administered orally twice daily (BID) (1400 mg/day) with food for 5 days (10 total doses) | 162 |
| 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)
Placebo: 2 × placebo to match PBI-0451(Pomotrelvir) tablets administered orally BID with food for 5 days (10 total doses) | 80 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | concurrent illness | 0 | 1 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Study drug non-compliance/ | 5 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | PBI-0451 (Pomotrelvir) |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 2 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 240 Participants | 161 Participants |
| Age, Continuous | 42.4 years STANDARD_DEVIATION 11.75 | 42.6 years STANDARD_DEVIATION 12.09 | 42.7 years STANDARD_DEVIATION 12.29 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 80 Participants | 242 Participants | 162 Participants |
| Sex: Female, Male Female | 42 Participants | 127 Participants | 85 Participants |
| Sex: Female, Male Male | 38 Participants | 115 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 162 | 0 / 80 |
| other Total, other adverse events | 22 / 162 | 4 / 80 |
| serious Total, serious adverse events | 1 / 162 | 0 / 80 |
Outcome results
Primary
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.
Time frame: Day 3
Population: The mITTV analysis set included a subset of the mITT anaylsis set who had detectable infectious SARS-CoV-2 at baseline/Day 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PBI-0451 (Pomotrelvir) | Virologic Efficacy of PBI-0451 (Pomotrelvir) | 37 Participants |
| Placebo | Virologic Efficacy of PBI-0451 (Pomotrelvir) | 20 Participants |
Secondary
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.
Time frame: Day 1-28
Population: The median number of days to cessation of 14 targeted CVOID-19 symptoms reported at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PBI-0451 (Pomotrelvir) | Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 1-28 | 10 days |
| Placebo | Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 1-28 | 11 days |
Secondary
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
Time frame: Day 1 - 28
Population: Participants who met sustained resolution of symptoms through Day 28
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PBI-0451 (Pomotrelvir) | Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 28 | 132 participants |
| Placebo | Clinical Efficacy of PBI-0451(Pomotrelvir) Versus Placebo Through Study Day 28 | 66 participants |
Secondary
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)
Time frame: Day 1-28
Population: Numbers reflect subjects with sufficient viral load at baselline for whole genome sequencing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PBI-0451 (Pomotrelvir) | Effect of PBI-0451(Pomotrelvir) on SARS-CoV-2 | 37 Participants |
| Placebo | Effect of PBI-0451(Pomotrelvir) on SARS-CoV-2 | 20 Participants |
Secondary
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
Time frame: Day 1-28
Population: The safety analysis set included all randomized participants who received ≥ 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PBI-0451 (Pomotrelvir) | Safety and Tolerability of PBI-0451(Pomotrelvir) | Serious Adverse Events | 1 events |
| PBI-0451 (Pomotrelvir) | Safety and Tolerability of PBI-0451(Pomotrelvir) | Grade 3 Lab Abnormalities | 15 events |
| PBI-0451 (Pomotrelvir) | Safety and Tolerability of PBI-0451(Pomotrelvir) | Discontinuation of study drug due to AEs | 1 events |
| PBI-0451 (Pomotrelvir) | Safety and Tolerability of PBI-0451(Pomotrelvir) | Grade 4 Lab Abnormalities | 1 events |
| PBI-0451 (Pomotrelvir) | Safety and Tolerability of PBI-0451(Pomotrelvir) | Adverse Events | 26 events |
| Placebo | Safety and Tolerability of PBI-0451(Pomotrelvir) | Grade 4 Lab Abnormalities | 3 events |
| Placebo | Safety and Tolerability of PBI-0451(Pomotrelvir) | Adverse Events | 4 events |
| Placebo | Safety and Tolerability of PBI-0451(Pomotrelvir) | Serious Adverse Events | 0 events |
| Placebo | Safety and Tolerability of PBI-0451(Pomotrelvir) | Discontinuation of study drug due to AEs | 0 events |
| Placebo | Safety and Tolerability of PBI-0451(Pomotrelvir) | Grade 3 Lab Abnormalities | 4 events |
Other Pre-specified
Incidence of Rebound SARS-CoV-2 Infection
Percentage of participantss with clinical and/or virologic rebound
Time frame: Day 1-28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PBI-0451 (Pomotrelvir) | Incidence of Rebound SARS-CoV-2 Infection | 14 Participants |
| Placebo | Incidence of Rebound SARS-CoV-2 Infection | 2 Participants |