Coronavirus Infection, Covid-19, SARS-CoV-2
Conditions
Brief summary
This pilot study is being performed to assess the efficacy and safety of inhaled ensifentrine delivered via pMDI compared with a matching placebo in conjunction with standard of care treatments on recovery in patients hospitalized due to COVID-19 infection.
Detailed description
Expploratory endpoint, pilot study, not statistically powered go to protocol
Interventions
DRUGEnsifentrine Dose 1
Study drug delivered twice daily via pMDI
DRUGPlacebo pMDI
Placebo delivered twice daily via pMDI
Sponsors
Verona Pharma 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 80 Years
Healthy volunteers
No
Inclusion criteria
* Capable of giving informed consent indicating that they understand the purpose of the study and study procedures and agree to comply with the requirements and restrictions listed in the informed consent form and in this protocol. * Patient must be at least 18 years of age and less than or equal to 80 years of age at the time of informed consent. * Males are eligible to participate or females of non-childbearing potential or WOCBP who have a negative pregnancy test at screening are eligible to participate. WOCBP and female partners of male participants agree to either abstinence or use at least one primary form of highly effective contraception not including hormonal contraception from the time of screening through Day 60 following the first dose of study medication. * Clinical status consistent with 3, 4 or 5 on the Ordinal scale: Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring any supplemental oxygen; Hospitalized, requiring non-invasive ventilation or use of high flow oxygen devices. * Admission to hospital AND have a confirmed diagnosis of severe acute respiratory syndrome coronavirus (SARS-COV-2) infection confirmed by polymerase chain reaction (PCR) test AND displays at least one of the following: Respiratory rate \> 24 breaths per minute; new cough; new atypical chest pain; new dyspnea; oxygen saturation \< 97% at rest; chest x-ray with new changes consistent with COVID-related airspace disease. * Capable of complying with all study restrictions and procedures including ability to use the pMDI correctly.
Exclusion criteria
* Participation in any other clinical trial of an experimental treatment for COVID-19, unless related to an expanded access program as part of Standard of Care at screening or during study. * Evidence of multiorgan failure. * Requiring mechanical ventilation at screening. * Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 X upper limit of normal (ULN) at screening. * Creatinine clearance \< 30 mL/min at screening. * Pregnancy or lactation at screening. * Allergy or other contraindication or one of ensifentrine. * In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments. * Use of prohibited medications (theophylline, PDE4 inhibitors \[e.g. roflumilast, apremilast, crisaborole\] within 48 hours of screening or during study) * Any other reason that the Investigator considers makes the patient unsuitable to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Recovery | Day 29 | Recovery = first day on which subject satisfies one of the following categories: not hospitalized, no limitations of activities; or not hospitalized, limitation of activities, home oxygen requirement, or both. |
Countries
United States
Participant flow
Recruitment details
45 patients hospitalized with COVID-19 enrolled and randomized.
Pre-assignment details
45 patients randomized to receive either RPL554 2mg via pMDI BID or placebo via pMDI BID in addition to standard of care treatment for COVID-19 disease until discharged or Day 29, whichever was first.
Participants by arm
| Arm | Count |
|---|---|
| Ensifentrine + Standard of Care 30 subjects randomized to receive blinded, inhaled ensifentrine in addition to standard of care treatment for COVID-19 infection
Ensifentrine Dose 1: Study drug delivered twice daily via pMDI | 30 |
| Placebo + Standard of Care 15 subjects randomized to receive blinded, inhaled placebo in addition to standard of care treatment for COVID-19 infection
Placebo pMDI: Placebo delivered twice daily via pMDI | 15 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo + Standard of Care | Ensifentrine + Standard of Care |
|---|---|---|---|
| 2 or more Co-Morbidities | 20 Participants | 4 Participants | 16 Participants |
| Age, Continuous | 56.3 years STANDARD_DEVIATION 14 | 51.5 years STANDARD_DEVIATION 14.7 | 58.7 years STANDARD_DEVIATION 13.3 |
| COVID-19 Disease Severity (Moderate) | 45 Participants | 15 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 14 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 8 Participants | 21 Participants |
| Region of Enrollment United States | 45 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 28 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 17 Participants | 6 Participants | 11 Participants |
| Smoking Status (Current) | 1 Participants | 1 Participants | 0 Participants |
| Smoking Status (Previous) | 8 Participants | 1 Participants | 7 Participants |
| Supplemental Oxygen Use (Yes) | 44 Participants | 14 Participants | 30 Participants |
| Systolic Blood Pressure | 138 mmHg | 124 mmHg | 145 mmHg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 30 | 0 / 15 |
| other Total, other adverse events | 5 / 30 | 3 / 15 |
| serious Total, serious adverse events | 1 / 30 | 0 / 15 |
Outcome results
Primary
Proportion of Patients With Recovery
Recovery = first day on which subject satisfies one of the following categories: not hospitalized, no limitations of activities; or not hospitalized, limitation of activities, home oxygen requirement, or both.
Time frame: Day 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ensifentrine + Standard of Care | Proportion of Patients With Recovery | 29 Participants |
| Placebo + Standard of Care | Proportion of Patients With Recovery | 15 Participants |
p-value: 1Fisher Exact