Study of Ensifentrine or Placebo Delivered Via pMDI in Hospitalized Patients With COVID-19

• ClinicalTrials.gov Identifier: NCT04527471
• Recruitment Status: Active, not recruiting
• First Posted: August 26, 2020
• Last Update Posted: January 15, 2021
• Sponsor: Verona Pharma Inc
• Information provided by (Responsible Party): Verona Pharma plc ( Verona Pharma Inc )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Coronavirus Infection; Covid-19; SARS-CoV-2	Drug: Ensifentrine Dose 1; Drug: Placebo pMDI	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Single-center, Pilot, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Ensifentrine in the Recovery of Hospitalized Patients With COVID-19
• Actual Study Start Date: September 4, 2020
• Estimated Primary Completion Date: February 2021
• Estimated Study Completion Date: March 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Ensifentrine + Standard of Care; 30 subjects randomized to receive blinded, inhaled ensifentrine in addition to standard of care treatment for COVID-19 infection	Drug: Ensifentrine Dose 1; Study drug delivered twice daily via pMDI
Placebo Comparator: Placebo + Standard of Care; 15 subjects randomized to receive blinded, inhaled placebo in addition to standard of care treatment for COVID-19 infection	Drug: Placebo pMDI; Placebo delivered twice daily via pMDI

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with recovery [ Time Frame: 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.

Secondary Outcome Measures :

1. Time to recovery [ Time Frame: Day 1 to 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.
2. Proportion of patients with recovery [ Time Frame: Day 60 ]
3. Proportion of patients with improvement (from Day 1) of one category using the 7-point ordinal scale [ Time Frame: Days 7, 14 and 29 ]
4. Proportion of patients with improvement (from Day 1) of two categories using the 7-point ordinal scale [ Time Frame: Days 7, 14 and 29 ]
5. Mortality rate [ Time Frame: Days 29 and 60 ]
   All-cause mortality
6. Proportion of patients alive and not in respiratory failure [ Time Frame: Day 29 ]
   respiratory failure = requiring invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]
7. Proportion of patients needing re-hospitalization [ Time Frame: Day 60 ]
8. Duration of hospitalization from Day 1 [ Time Frame: Day 1 to Day 29 ]
9. Mean change from baseline in 7-point ordinal scale [ Time Frame: Days 7, 14 and 29 ]
10. Total time on supplemental oxygen [ Time Frame: Day 1 to Day 29 ]
11. Incidence of new non-invasive ventilation or high flow oxygen use [ Time Frame: Day 1 to Day 29 ]
12. Duration of new non-invasive ventilation or high flow oxygen use [ Time Frame: Day 1 to Day 29 ]
13. Incidence of new oxygen use [ Time Frame: Day 1 to Day 29 ]
14. Duration of new oxygen use [ Time Frame: Day 1 to Day 29 ]
15. Incidence of new mechanical ventilator use [ Time Frame: Day 1 to Day 29 ]
16. Duration of new mechanical ventilator use [ Time Frame: Day 1 to Day 29 ]
17. Proportion of patients receiving invasive mechanical ventilation or ECMO [ Time Frame: Days 7, 14 and 29 ]

Other Outcome Measures:

1. Incidence of Adverse Events (AEs) [ Time Frame: Day 60 ]
2. Respiration Rate [ Time Frame: Day 1 to Day 29 ]
   breaths/minute
3. Heart Rate [ Time Frame: Day 1 to Day 29 ]
   beats/minute
4. Body Temperature [ Time Frame: Day 1 to Day 29 ]
5. Blood Pressure [ Time Frame: Day 1 to Day 29 ]
   mmHg
6. Level of Consciousness [ Time Frame: Day 1 to Day 29 ]
   AVPU scale
7. Oxygen saturation [ Time Frame: Day 1 to Day 29 ]
   SpO2 %

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

The University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

Sponsors and Collaborators

Verona Pharma Inc

More Information

• Responsible Party: Verona Pharma Inc
• ClinicalTrials.gov Identifier: NCT04527471
• Other Study ID Numbers: RPL554-COV-201
• First Posted: August 26, 2020
• Last Update Posted: January 15, 2021
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Verona Pharma will not be sharing individual deidentified participant data or other relevant study documents.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Coronavirus Infections; Severe Acute Respiratory Syndrome; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases