A Phase 3 Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD

NCT04542057 | Completed Phase 3 Results FDA Drug

• 1 other identifier: RPL554-CO-302
• Study Type: interventional
• Target: 790
• Locations: 9 countries
• Sites: 129

Brief Summary

The purpose of this study is to determine if ensifentrine is safe and effective for the treatment of patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD

Outcome Measures

Primary Outcomes (1)

• Least Square (LS) Mean Change From Baseline in Average Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) at Week 12

  Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Average FEV1 AUC0-12h was defined as AUC over 12 hours of the FEV1, divided by 12 hours. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, \<=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.

  Baseline (40 minutes before first administration on Day 1) and Week 12

Secondary Outcomes (9)

• LS Mean Change From Baseline FEV1 to Peak FEV1 at Day 1 and Weeks 6, 12 and 24

  Baseline (40 minutes before first administration on Day 1), post-dose on Day 1, Weeks 6, 12, and 24

• LS Mean Change From Baseline to the Mean Weekly Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24

  Baseline (average of 7 days before first administration on Day 1) and Weeks 6, 12, and 24

• LS Mean Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 6, 12 and 24

  Baseline (40 minutes before first administration on Day 1) and Weeks 6, 12, and 24

• LS Mean Change From Baseline FEV1 to Morning Trough FEV1 at Weeks 6, 12 and 24

  Baseline (40 minutes before first administration on Day 1) and Weeks 6, 12, and 24

• LS Mean Change From Baseline in Average FEV1 Area Under the Curve Over 4 Hours (AUC0-4h) at Day 1 and Weeks 6, 12 and 24

  Baseline (40 minutes before first administration on Day 1), post-dose on Day 1, Weeks 6, 12, and 24

Study Arms (2)

Arm 1

EXPERIMENTAL

Ensifentrine Nebulized Suspension; 3 mg twice daily for 24 weeks

Drug: Ensifentrine

Arm 2

PLACEBO COMPARATOR

Ensifentrine Placebo Nebulized Solution; twice daily for 24 weeks

Drug: Placebo

Interventions

Ensifentrine DRUG

Dosage Formulation: Ensifentrine Nebulizer suspension Dosage 3mg Frequency: Twice Daily for 24 weeks

Arm 1

Placebo DRUG

Dosage Formulation: Ensifentrine Placebo Nebulizer solution Frequency: Twice Daily for 24 weeks

Arm 2

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent
• 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 (ICF).
• Age and Sex
• Age: Patient must be 40 to 80 years of age inclusive, at the time of Screening.
• Sex:
• Males are eligible to participate if they agree to use contraception as described in the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.
• Females are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions apply:
• Not a woman of childbearing potential (WOCBP). Or
• A WOCBP who agrees to follow the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.
• Smoking History
• Smoking History: Current or former cigarette smokers with a history of cigarette smoking ≥10 pack years at Screening (Visit 0) \[number of pack years = (number of cigarettes per day / 20) × number of years smoked (eg, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Pipe and/or cigar use cannot be used to calculate pack-year history. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 0. Smoking cessation programs are permitted during the study.
• COPD Diagnosis, Symptoms, Severity and Maintenance Therapy
• COPD Diagnosis: Patients with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (Celli BR, 2004) with symptoms compatible with COPD.
• COPD Symptoms: A score of ≥2 on the Modified Medical Research Council (mMRC) Dyspnea Scale.
• COPD Severity:

You may not qualify if:

• Current Condition or Medical History
• History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
• Hospitalizations for COPD, pneumonia, or Corona Virus Disease 2019 (COVID-19) in the 12 weeks prior to Screening and/or a positive COVID-19 test result indicating an active infection at Screening. Patients with COVID-19 antibodies from a previous exposure with no active infection are not excluded.
• COPD exacerbation requiring oral or parenteral steroids within 3 months of Screening.
• Previous lung resection or lung reduction surgery within 1-year of Screening.
• Pulmonary rehabilitation, unless such treatment has been in a stable maintenance phase for 4 weeks prior to Visit 1 and remains stable during the study.
• Lower respiratory tract infection within 6 weeks of Screening.
• Other respiratory disorders including, but not limited to, a current diagnosis of asthma, active tuberculosis, lung cancer, sarcoidosis, lung fibrosis, interstitial lung diseases, unstable sleep apnea, known alpha-1 antitrypsin deficiency, core pulmonale, clinically significant pulmonary hypertension, clinically significant bronchiectasis, or other active pulmonary diseases.
• Major surgery (requiring general anesthesia) in the 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.
• Historical or current evidence of clinically significant cardiovascular disease defined as any disease that in the opinion of the Investigator would put the safety of the patient at risk through participation or which could affect the efficacy or safety analysis if the disease/condition were to exacerbate during the study, including, but not limited to:
• Myocardial infarction or unstable angina within 6 months prior to Screening.
• Unstable or life-threatening cardiac arrhythmia requiring intervention within 3 months prior to Screening.
• Diagnosis of New York Heart Association Class III and Class IV heart failure.
• Chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant.
• Unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).

Sponsors & Collaborators

• Verona Pharma plc: lead
• Iqvia Pty Ltd: collaborator

Study Sites (130)

Wright Clinical Research, LLC

Alabaster, Alabama, 35007, United States

Location

SEC Clinical Research

Andalusia, Alabama, 36420, United States

Location

Jasper Summit Research LLC

Jasper, Alabama, 35501, United States

Location

Pulmonary Associates Clinical Trials

Phoenix, Arizona, 85006, United States

Location

Elite Clinical Studies LLC

Phoenix, Arizona, 85018, United States

Location

Clinical Research Institute of Arizona, LLC

Sun City West, Arizona, 85375, United States

Location

Premier Medical Group

Bakersfield, California, 93309, United States

Location

Antelope Valley Clinical Trials

Lancaster, California, 93534, United States

Location

Downtown LA Research Center, Inc.

Los Angeles, California, 90017, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

California Medical Research Associates

Northridge, California, 91324, United States

Location

Center for Clinical Trials of Sacramento, Inc.

Sacramento, California, 95823, United States

Location

Integrated Research Center

San Diego, California, 92117, United States

Location

Institute of HealthCare Assessment, Inc.

San Diego, California, 92120, United States

Location

Alpine Clinical Research Center

Boulder, Colorado, 80301, United States

Location

Innovative Research of West Florida

Clearwater, Florida, 33756, United States

Location

Clinical Research of West Florida, Inc.

Clearwater, Florida, 33765, United States

Location

Accel Research Sites - DeLand Clinical Research Unit

DeLand, Florida, 32720, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Medical Research of Central Florida

Leesburg, Florida, 34748, United States

Location

Axcess Medical Research

Loxahatchee Groves, Florida, 13005, United States

Location

Research Institute of South Florida

Miami, Florida, 33173, United States

Location

Advanced Medical Research Institute

Miami, Florida, 33174, United States

Location

Clinical Trials of Florida. LLC

Miami, Florida, 33186, United States

Location

South Medical Research Group, Inc.

Miami, Florida, 33186, United States

Location

ProCare Clinical Research

Miami Gardens, Florida, 33014, United States

Location

HMD Research, LLC

Orlando, Florida, 32819, United States

Location

Florida Institute for Clinical Research

Orlando, Florida, 32825, United States

Location

Sarasota Clinical Research

Sarasota, Florida, 34239, United States

Location

Coastal Pulmonary Critical Care

St. Petersburg, Florida, 33704, United States

Location

Pasadena Center for Medical Research, LLC

St. Petersburg, Florida, 33707, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33606, United States

Location

Clinical Research Trials of Florida, Inc.

Tampa, Florida, 33607, United States

Location

Florida Pulmonary Research Institute, LLC

Winter Park, Florida, 32789, United States

Location

AMR New Orleans

New Orleans, Louisiana, 70119, United States

Location

Genesis Clin RES& Consulting

Fall River, Massachusetts, 02723, United States

Location

Minnesota Lung Center

Edina, Minnesota, 55435, United States

Location

Minnesota Lung Center

Woodbury, Minnesota, 55125, United States

Location

Midwest Chest Consultants

Saint Charles, Missouri, 63301, United States

Location

Montana Medical Research Inc.

Missoula, Montana, 59808, United States

Location

Mid Hudson Medical Research

New Windsor, New York, 12553, United States

Location

CHEAR Center LLC

The Bronx, New York, 10455, United States

Location

Carolina Clinical Research

Charlotte, North Carolina, 28273, United States

Location

American Health Research

Charlotte, North Carolina, 28277, United States

Location

Clinical Research of Gastonia

Gastonia, North Carolina, 28054, United States

Location

PharmQuest LLC

Greensboro, North Carolina, 27408, United States

Location

Monroe Biomedical Research

Monroe, North Carolina, 28112, United States

Location

Clinical Research of Lake Norman

Mooresville, North Carolina, 28117, United States

Location

Carolina Research Center, Inc.

Shelby, North Carolina, 28150, United States

Location

Aventiv Research Inc.

Columbus, Ohio, 43213, United States

Location

Remington Davis Clinical Research

Columbus, Ohio, 43215, United States

Location

Aventiv Research

Dublin, Ohio, 43106, United States

Location

OK Clinical Research, LLC

Edmond, Oklahoma, 73034, United States

Location

Velocity Clinical Research, Medford (Crisor, LLC)

Medford, Oregon, 97504, United States

Location

Safe Harbor Clinical Research

East Providence, Rhode Island, 02914, United States

Location

VitaLink Research Anderson

Anderson, South Carolina, 29621, United States

Location

Lowcountry Lung and Critical Care, P.A.

Charleston, South Carolina, 29406, United States

Location

VitaLink Research Columbia

Columbia, South Carolina, 29204, United States

Location

Piedmont Research Partners

Fort Mill, South Carolina, 29707, United States

Location

VitaLink Research Gaffney

Gaffney, South Carolina, 29340, United States

Location

VitaLink Research - Greenville

Greenville, South Carolina, 29615, United States

Location

Clinical Research of Rock Hill

Rock Hill, South Carolina, 29732, United States

Location

Spartanburg Medical Research

Spartanburg, South Carolina, 29303, United States

Location

VitaLink Research Spartanburg

Spartanburg, South Carolina, 29303, United States

Location

CU Pharmaceutical Research

Union, South Carolina, 29379, United States

Location

MultiSpecialty Clinical Research, Inc.

Johnson City, Tennessee, 37601, United States

Location

New Phase Research Development

Knoxville, Tennessee, 37909, United States

Location

PnP Research

Amarillo, Texas, 79106, United States

Location

TTS Research

Boerne, Texas, 78006, United States

Location

Corsicana Medical Research, PLLC

Corsicana, Texas, 75110, United States

Location

Houston Pulmonary and Sleep Allergy and Asthma Associates

Cypress, Texas, 77429, United States

Location

Metroplex Pulmonary and Sleep Center

McKinney, Texas, 75069, United States

Location

Diagnostics Research Group

San Antonio, Texas, 78229, United States

Location

Element Research Group

San Antonio, Texas, 78258, United States

Location

Sherman Clinical Research

Sherman, Texas, 75092, United States

Location

DM Clinical Research

Tomball, Texas, 77375, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

UZA

Edegem, 2650, Belgium

Location

C.H.R. de la Citadelle

Liège, 4000, Belgium

Location

Private Practice RESPISOM Namur

Namur, 5101, Belgium

Location

AZ Delta

Roeselare, 8800, Belgium

Location

MHAT 'Puls' AD

Blagoevgrad, 2700, Bulgaria

Location

Medical Centre "Asklepii", OOD

Dupnitsa, 2600, Bulgaria

Location

MHAT 'Dr. Stamen Iliev', AD

Montana, 3400, Bulgaria

Location

SHATPPD - Pazardzhik, EOOD

Pazardzhik, 4400, Bulgaria

Location

SHATPD Pernik

Pernik, 2305, Bulgaria

Location

Medical Center- Prolet Ltd

Rousse, 7000, Bulgaria

Location

SHATPPD-Ruse EOOD

Rousse, 7002, Bulgaria

Location

University First MHAT-Sofia, "St. Joan Krastitel" EAD

Sofia, 1142, Bulgaria

Location

Fifth MHAT - Sofia EAD

Sofia, 1233, Bulgaria

Location

NMTH "Tsar Boris III"

Sofia, 1233, Bulgaria

Location

MHAT "Lyulin", EAD

Sofia, 1336, Bulgaria

Location

DCC "Alexandrovska", EOOD

Sofia, 1431, Bulgaria

Location

Diagnostic Consultation Center CONVEX EOOD

Sofia, 1680, Bulgaria

Location

Medical Center "Nov Rehabilitatsionen Tsentar", EOOD

Stara Zagora, 6000, Bulgaria

Location

Medical Center "ResearchExpert", OOD

Varna, 9000, Bulgaria

Location

MC "Tara", OOD

Veliko Tarnovo, 5000, Bulgaria

Location

SHATPPD "Dr. Treyman" EOOD

Veliko Tarnovo, 5000, Bulgaria

Location

SHATPPD - Vratsa, EOOD

Vratsa, 3000, Bulgaria

Location

ALTA Clinical Research Inc.

Edmonton, Alberta, T5A 4L8, Canada

Location

Synergy Respiratory Care

Sherwood Park, Alberta, T8H 0N2, Canada

Location

Dynamic Drug Advancement

Ajax, Ontario, LIS 2J5, Canada

Location

Respirology and Rheumatology Associates

Windsor, Ontario, N8X 1T3, Canada

Location

C.I.C. Mauricie Inc.

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

Zealand University Hospital, Roskilde

Roskilde, 4000, Denmark

Location

Tartu University Hospital, Lung Clinic

Tartu, 50411, Estonia

Location

Dr. Kenessey Albert Kórház-Rendelőintézet, Pulmonológiai Osztály

Balassagyarmat, 2660, Hungary

Location

Komlói Egészségcentrum, Bányászati Utókezelő és Éjjeli Szanatórium Egészségügyi Központ

Komló, 7300, Hungary

Location

Da Vinci Klinika Infer-Med Kft. Tüdőgyógyászat

Pécs, 7634, Hungary

Location

Szarvasi Tüdőgyógyász Kft

Szarvas, 5540, Hungary

Location

Csanád-Csongrád Megyei Mellkasi Betegségek Szakkórháza, Tüdőgondozó Intézet

Szeged, 6722, Hungary

Location

Szent Borbála Kórház, Tüdőgyógyászat

Tatabánya, 2800, Hungary

Location

Centrum Medyczne All-Med

Krakow, 30-033, Poland

Location

Małopolskie Centrum Alergologii

Krakow, 31-624, Poland

Location

ETG Łódź

Lodz, 90-302, Poland

Location

Ostrowieckie Centrum Medyczne spółka cywilna Anna Olech-Cudzik, Krzysztof Cudzik

Ostrowiec Świętokrzyski, 27-400, Poland

Location

Prywatny Gabinet Lekarski

Rzeszów, 35-051, Poland

Location

Gabinet Pulmonologii i Diagnostyki Chorób Alergicznych

Szczecin, 70-111, Poland

Location

Centrum Badań Klinicznych Piotr Napora Lekarze Spółka Partnerska

Wroclaw, 51-162, Poland

Location

"ALL-MED" Specjalistyczna Opieka Medyczna, Medyczny Instytut Badawczy

Wroclaw, 53-201, Poland

Location

Pneumologicko-ftizeologická ambulancia, Pneumomed, s.r.o

Bratislava, 851 01, Slovakia

Location

Zeleznicna nemocnica s poliklinikou

Košice, 04001, Slovakia

Location

Ambulancia pneumologie a ftizeologie, ZAPA JJ, s.r.o.

Levice, 93401, Slovakia

Location

Univerzitna nemocnica Martin, Klinika pneumologie a ftizeologie

Martin, 03659, Slovakia

Location

Hospital Vithas Internacional Xanit

Benalmádena, Málaga, 29631, Spain

Location

Institut Catala de Serveis Medics

Girona, 17005, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 45010, Spain

Location

Related Publications (4)

• Dransfield M, Marchetti N, Kalhan R, Reyner D, Dixon AL, Rheault T, Rickard KA, Anzueto A. Ensifentrine in COPD patients taking long-acting bronchodilators: A pooled post-hoc analysis of the ENHANCE-1/2 studies. Chron Respir Dis. 2025 Jan-Dec;22:14799731251314874. doi: 10.1177/14799731251314874.

  PMID: 39854278 DERIVED

• Sciurba FC, Christenson SA, Rheault T, Bengtsson T, Rickard K, Barjaktarevic IZ. Effect of Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine on Exacerbation Rate and Risk in Patients With Moderate to Severe COPD. Chest. 2025 Feb;167(2):425-435. doi: 10.1016/j.chest.2024.07.168. Epub 2024 Aug 27.

  PMID: 39197510 DERIVED

• Mahler DA, Bhatt SP, Rheault T, Reyner D, Bengtsson T, Dixon A, Rickard K, Singh D. Effect of ensifentrine on dyspnea in patients with moderate-to-severe chronic obstructive pulmonary disease: pooled analysis of the ENHANCE trials. Expert Rev Respir Med. 2024 Aug;18(8):645-654. doi: 10.1080/17476348.2024.2389960. Epub 2024 Aug 8.

  PMID: 39106052 DERIVED

• Anzueto A, Barjaktarevic IZ, Siler TM, Rheault T, Bengtsson T, Rickard K, Sciurba F. Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase III Trials (the ENHANCE Trials). Am J Respir Crit Care Med. 2023 Aug 15;208(4):406-416. doi: 10.1164/rccm.202306-0944OC.

  PMID: 37364283 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ensifentrine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Verona Pharma plc

info@veronapharma.com

See email

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: September 9, 2020
• Study Start: September 22, 2020
• Primary Completion: May 3, 2022
• Study Completion: July 6, 2022
• Last Updated: October 16, 2023
• Results First Posted: July 24, 2023

Record last verified: 2023-10

Locations

BE (4); HU (6); DK (3); ES (4); CA (5); US (77); SL (4); BU (18); PL (8)