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

• ClinicalTrials.gov Identifier: NCT04527471
• Recruitment Status: Completed
• First Posted: August 26, 2020
• Results First Posted: September 22, 2022
• Last Update Posted: September 22, 2022
• Sponsor: Verona Pharma Inc
• Information provided by (Responsible Party): Verona Pharma plc ( Verona Pharma Inc )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Coronavirus Infection; Covid-19; SARS-CoV-2
• Interventions: Drug: Ensifentrine Dose 1; Drug: Placebo pMDI
• Enrollment: 45

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.

Arm/Group Title	Ensifentrine + Standard of Care	Placebo + Standard of Care
Arm/Group Description	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	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
Period Title: Overall Study
Started	30	15
Hospitalized up to 7 Days	24	12
Hospitalized for > 7 Days	6	3
Completed [1]	28	15
Not Completed	2	0
Reason Not Completed
Adverse Event	1	0
Lost to Follow-up	1	0
[1] Through Day 60 Follow-up

Baseline Characteristics

Arm/Group Title		Ensifentrine + Standard of Care	Placebo + Standard of Care	Total
Arm/Group Description		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	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	Total of all reporting groups
Overall Number of Baseline Participants		30	15	45
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	30 participants	15 participants	45 participants
		58.7 (13.3)	51.5 (14.7)	56.3 (14.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	15 participants	45 participants
	Female	19 63.3%	9 60.0%	28 62.2%
	Male	11 36.7%	6 40.0%	17 37.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	15 participants	45 participants
	Hispanic or Latino	0 0.0%	1 6.7%	1 2.2%
	Not Hispanic or Latino	30 100.0%	14 93.3%	44 97.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	15 participants	45 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 6.7%	1 2.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	9 30.0%	6 40.0%	15 33.3%
	White	21 70.0%	8 53.3%	29 64.4%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	30 participants	15 participants	45 participants
		30	15	45
COVID-19 Disease Severity (Moderate); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	15 participants	45 participants
		30 100.0%	15 100.0%	45 100.0%
Smoking Status (Previous); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	15 participants	45 participants
		7 23.3%	1 6.7%	8 17.8%
Supplemental Oxygen Use (Yes); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	15 participants	45 participants
		30 100.0%	14 93.3%	44 97.8%
2 or more Co-Morbidities; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	15 participants	45 participants
		16 53.3%	4 26.7%	20 44.4%
Systolic Blood Pressure; Median (Full Range); Unit of measure: mmHg
	Number Analyzed	30 participants	15 participants	45 participants
		145; (86 to 174)	124; (96 to 170)	138; (86 to 174)
Smoking Status (Current); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	15 participants	45 participants
		0 0.0%	1 6.7%	1 2.2%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With Recovery
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ensifentrine + Standard of Care	Placebo + Standard of Care
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	30	15
Measure Type: Count of Participants; Unit of Measure: Participants
	29 96.7%	15 100.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ensifentrine + Standard of Care, Placebo + Standard of Care
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	1
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Adverse Events

Time Frame	Over 60 days
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Ensifentrine + Standard of Care	Placebo + Standard of Care
Arm/Group Description	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	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
All-Cause Mortality
	Ensifentrine + Standard of Care	Placebo + Standard of Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/30 (3.33%)	0/15 (0.00%)
Serious Adverse Events
	Ensifentrine + Standard of Care	Placebo + Standard of Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/30 (3.33%)	0/15 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/30 (3.33%)	0/15 (0.00%)
1 Term from vocabulary, MedRA 21.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Ensifentrine + Standard of Care	Placebo + Standard of Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/30 (16.67%)	3/15 (20.00%)
Cardiac disorders
Sinus bradycardia and Atrioventricular block first degree † 1	1/30 (3.33%)	0/15 (0.00%)
Gastrointestinal disorders
Diarrhoea † 1	1/30 (3.33%)	0/15 (0.00%)
General disorders
Oedema peripheral † 1	0/30 (0.00%)	1/15 (6.67%)
Investigations
Alanine aminotransferase increased † 1	1/30 (3.33%)	1/15 (6.67%)
Aspartate aminotransferase increased † 1	1/30 (3.33%)	1/15 (6.67%)
Blood bilirubin increased † 1	1/30 (3.33%)	0/15 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	1/30 (3.33%)	0/15 (0.00%)
Hyperglycemia † 1	1/30 (3.33%)	0/15 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia † 1	1/30 (3.33%)	1/15 (6.67%)
Dry skin † 1	1/30 (3.33%)	0/15 (0.00%)
Vascular disorders
Hypertension † 1	1/30 (3.33%)	0/15 (0.00%)
1 Term from vocabulary, MedDRA (21.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

This was an un-powered pilot study of ensifentrine pMDI in patients hospitalized for moderate COVID-19 infection.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Margot MacDonald-berko
• Organization: Verona Pharma
• Phone: 833-417-0262
• EMail: margot.macdonald-berko@veronapharma.com

• Responsible Party: Verona Pharma plc ( Verona Pharma Inc )
• ClinicalTrials.gov Identifier: NCT04527471
• Other Study ID Numbers: RPL554-COV-201
• First Submitted: August 6, 2020
• First Posted: August 26, 2020
• Results First Submitted: August 26, 2022
• Results First Posted: September 22, 2022
• Last Update Posted: September 22, 2022