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

NCT04535986 | Completed Phase 3 Results FDA Drug

• 1 other identifier: RPL554-CO-301
• Study Type: interventional
• Target: 763
• Locations: 12 countries
• Sites: 122

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of ensifentrine in 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 (pre-dose 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 (pre-dose 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 (pre-dose 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 (pre-dose 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 (pre-dose 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 (pre-dose on Day 1), post-dose on Day 1, Weeks 6, 12, and 24

Study Arms (2)

Arm 1

EXPERIMENTAL

Ensifentrine Nebulized Suspension; 3 mg BID

Drug: Ensifentrine

Arm 2

PLACEBO COMPARATOR

Placebo Nebulized BID

Drug: Placebo

Interventions

Ensifentrine DRUG

Dosage Formulation: Ensifentrine Nebulizer suspension Dosage 3mg Frequency: Twice Daily for 24 weeks or 48 weeks

Arm 1

Placebo DRUG

Dosage Formulation: Ensifentrine Placebo Nebulizer solution Frequency: Twice Daily for 24 weeks or 48 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) as defined in 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 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 (122)

Phoenix Medical Group

Peoria, Arizona, 85381, United States

Location

AMR Tempe

Tempe, Arizona, 85281, United States

Location

Beach Physicians Medical Group

Huntington Beach, California, 92647, United States

Location

Downtown LA Research Center, Inc.

Los Angeles, California, 90017, United States

Location

Clinical Research of West Florida, Inc.

Clearwater, Florida, 33765, United States

Location

St. Francis Medical Institute

Clearwater, Florida, 33765, United States

Location

Qway Research, LLC

Hialeah, Florida, 33010, United States

Location

Multi-Specialty Research Associates, Inc.

Lake City, Florida, 32055, United States

Location

Elite Clinical Research

Miami, Florida, 33144, United States

Location

Global Research Solutions Corp

Miami, Florida, 33144, United States

Location

Phoenix Medical Research

Miami, Florida, 33165, United States

Location

Florida Institute for Clinical Research

Orlando, Florida, 32825, United States

Location

Precision Clinical Research

Sunrise, Florida, 33351, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33606, United States

Location

iResearch Atlanta, LLC

Decatur, Georgia, 30030, United States

Location

IACT Health

Rincon, Georgia, 31326, United States

Location

In-Quest Medical Research, LLC

Suwanee, Georgia, 30024, United States

Location

John Hopkins University School of Medicine

Baltimore, Maryland, 21224, United States

Location

Pulmonary Research Institute of SE Michigan

Farmington Hills, Michigan, 48336, United States

Location

Midwest Chest Consultants

Saint Charles, Missouri, 63301, United States

Location

The Clinical Research Center, LLC

St Louis, Missouri, 63141, United States

Location

Sierra Clinical Research

Las Vegas, Nevada, 89106, United States

Location

Alliance for Multispecialty Research, LLC

Las Vegas, Nevada, 89119, United States

Location

IMA Clinical Research, LLC

New York, New York, 10036, United States

Location

Monroe Biomedical Research

Monroe, North Carolina, 28112, United States

Location

Remington Davis Clinical Research

Columbus, Ohio, 43215, United States

Location

Velocity Clinical Research - Grants Pass

Grants Pass, Oregon, 97527, United States

Location

Clinical Research Associates of Central PA, LLC

DuBois, Pennsylvania, 15801, United States

Location

University of Pittsburgh Physicians, Emphysema/COPD Research Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medtrial

Columbia, South Carolina, 29204, United States

Location

MDFirst Research

Lancaster, South Carolina, 29720, United States

Location

Chattanooga Research & Medicine (CHARM)

Chattanooga, Tennessee, 37404, United States

Location

MultiSpecialty Clinical Research, Inc.

Johnson City, Tennessee, 37601, United States

Location

New Phase Research Development

Knoxville, Tennessee, 37909, United States

Location

West Houston Clinical Research Services

Houston, Texas, 77055, United States

Location

LinQ Research, LLC

Pearland, Texas, 77584, United States

Location

Sherman Clinical Research

Sherman, Texas, 75092, United States

Location

Pulmonary Research of Abingdon, LLC

Abingdon, Virginia, 24210, United States

Location

TPMG Clinical Research Williamsburg

Williamsburg, Virginia, 23188, United States

Location

SHATPPD - Haskovo, EOOD

Haskovo, 6300, Bulgaria

Location

Medical center Medconsult Pleven OOD

Pleven, 5800, Bulgaria

Location

UMHAT-Plovdiv AD

Plovdiv, 4003, Bulgaria

Location

Medical Center Hera EOOD

Sofia, 1510, Bulgaria

Location

MC "Sv. Ivan Rilski", OOD

Vidin, 3700, Bulgaria

Location

MUDr. I. Cierna Peterova s.r.o.

Brandýs nad Labem, 25001, Czechia

Location

Fakultni nemocnice Brno, Dept of Klinika nemoci plicnich a tuberkulozy

Brno, 625 00, Czechia

Location

EDUMED s.r.o.

Broumov, 550 01, Czechia

Location

MUDr. Petr Pravda

Hlučín, 74801, Czechia

Location

MediTrial s.r.o.

Jindřichův Hradec, 377 01, Czechia

Location

Plicni ambulance Kralupy s.r.o.

Kralupy nad Vltavou, 278 01, Czechia

Location

CEFISPIRO s.r.o.

Lovosice, 41002, Czechia

Location

Odborná plicní ambulance Opava s.r.o.

Opava, 74601, Czechia

Location

DAWON spol. s.r.o., Plicni ambulance

Prague, 149 00, Czechia

Location

Plicni centrum s.r.o.

Prague, 15300, Czechia

Location

MUDr. Josef Veverka, Plicni ambulacne

Rokycany, 33701, Czechia

Location

Plicni stredisko Teplice s.r.o.

Teplice, 41501, Czechia

Location

MECS GmbH Cottbus

Cottbus, Brandenburg, 03050, Germany

Location

Clinical Studies Pankow Dr Dr Evelin Liefring/Ishak Teber

Berlin, City state Bremen, 13187, Germany

Location

Praxis Dr. Keller

Frankfurt am Main, Hesse, 60389, Germany

Location

IKF Pneumologie GmbH & Co. KG

Frankfurt am Main, Hesse, 60596, Germany

Location

Dr. Christian Schlenska

Peine, Lower Saxony, 31224, Germany

Location

Zentrum fur Klinische Forschung

Cologne, North Rhine-Westphalia, 51069, Germany

Location

Framol-med GmbH, Pneumologische Gemeinschaftspraxis Rheine

Rheine, North Rhine-Westphalia, 48431, Germany

Location

Pneumologische Praxis Dr. Falk Brunner

Leipzig, Saxony, 04157, Germany

Location

Salvus-Klinische Studien GmbH.

Leipzig, Saxony, 04207, Germany

Location

SMO.MD GmbH

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

PRI Pulmonary Research Institute, Pneumologisches Forschungsinstitut GmbH

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

KLB Gesundheitsforschung Luebeck GmbH; Praxis Dr. med. Jens Becker

Lübeck, Schleswig-Holstein, 23552, Germany

Location

Studienpraxis Berlin-Brandenburg

Berlin, 10119, Germany

Location

Praxis an der Oper.

Berlin, 10625, Germany

Location

Ballenberger, Freytag, Wenisch Institut für klinische Forschung

Neu-Isenburg, 63263, Germany

Location

General Hospital of Athens of Chest Diseases "SOTIRIA", 7th Respiratory Clinic

Athens, 11527, Greece

Location

University General Hospital of Heraklion, Pulmonary Clinic

Heraklion, 71110, Greece

Location

University General Hospital of Ioannina, University Respiratory Clinic

Ioannina, 45500, Greece

Location

University General Hospital of Larissa, University Pulmonary Clinic

Larissa, 41110, Greece

Location

Clinexpert Kft.

Budapest, 1033, Hungary

Location

Szalay János Rendelőintézet Tüdőgyógyászati Szakrendelés

Hajdúnánás, 4080, Hungary

Location

Bajcsy-Zsilinszky Kórház és Rendelőintézet Monori Rendelőintézete

Monor, 2200, Hungary

Location

Karolina Kórház-Rendelőintézet, Tüdőgyógyászat

Mosonmagyaróvár, 9200, Hungary

Location

Püspökladányi Egészségügyi Szolgáltató Nonprofit Kft.

Püspökladány, 4150, Hungary

Location

Markusovszky Egyetemi Oktatókórház Tüdőgondozó

Szombathely, 9700, Hungary

Location

NZOZ Centrum Medyczne KERmed

Bydgoszcz, 85-231, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Centrum Alergologii Sp. z o. o.

Lublin, 20-552, Poland

Location

ETG Siedlce

Siedlce, 08-110, Poland

Location

NASZ LEKARZ Ośrodek Badań Klinicznych

Torun, 87-100, Poland

Location

ETG Warszawa

Warsaw, 02-793, Poland

Location

S.C Centrul Medical Unirea S.R.L, Campus Medical Brasov

Brasov, 500091, Romania

Location

S.C Centrul Medical de Diagnostic si Tratament Ambulator Neomed S.R.L

Brasov, 500283, Romania

Location

Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca

Brasov, 500366, Romania

Location

Quantum Medical Center S.R.L.

Bucharest, 012071, Romania

Location

Institutul de Pneumoftiziologie "Marius Nasta"

Bucharest, 050159, Romania

Location

S.C Cardiomed S.R.L

Cluj-Napoca, 400371, Romania

Location

Impatiens SRL

Codlea, 505100, Romania

Location

Fundatia Cardioprevent

Timișoara, 300134, Romania

Location

Spitalul Clinic de Boli Infectioase si Pneumoftiziologie "Dr. Victor Babes" Timisoara

Timișoara, 300310, Romania

Location

NSHI "Departmental CH on St. Barnaul of JSCO "Russian Railways"

Barnaul, 656038, Russia

Location

SBHI "Regional Clinical Hospital #3"

Chelyabinsk, 454091, Russia

Location

FSBI "Scientific-research Institute for Complex Problems of cardiovascular disease"

Kemerovo, 650002, Russia

Location

LLC "Novosibirsk GastroCenter"

Novosibirsk, 630007, Russia

Location

SBIH of Novosibirsk Region "Clinical Emergency Hospital #2"

Novosibirsk, 630008, Russia

Location

City Clinical Hospital #25

Novosibirsk, 630075, Russia

Location

SPb SBHI "Vvedenskaya hospital"

Saint Petersburg, 191180, Russia

Location

"LEC at the LLC "LLC "Energiy Zdorovya"

Saint Petersburg, 194156, Russia

Location

LLC "Institute of Medical Examinations"

Saint Petersburg, 196084, Russia

Location

Research center Eco-safety, LLC

Saint Petersburg, 196143, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

SPb SBIH "City Hospital # 40 of Kurortnyi region"

Sestroretsk, 197706, Russia

Location

SBHI of Yaroslavl Region "Clinical Hospital # 2"

Yaroslavl, 1500030, Russia

Location

SBHI of Yaroslavl Region "Clinical Hospital # 2"

Yaroslavl, 150010, Russia

Location

SBHI Outpatient 2

Yaroslavl, 150047, Russia

Location

LLC MA New Hospital

Yekaterinburg, 620109, Russia

Location

City Hospital #6

Yekaterinburg, 620149, Russia

Location

Nemocnica s poliklinikou Sv. Jakuba, n.o. Bardejov

Bardejov, 08501, Slovakia

Location

Inspiro, s.r.o.

Humenné, 06601, Slovakia

Location

Plucna ambulancia Hrebenar, s.r.o.

Spišská Nová Ves, 05201, Slovakia

Location

Yeungnam University Hospital

Daegu, 42415, South Korea

Location

Kyung Hee University Hospital

Seoul, 02447, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

The Catholic University of Korea, Yeouido St.Mary's Hospital

Seoul, 07345, South Korea

Location

Respiratory Clinical Trials Ltd

London, Greater London, W1T6AH, United Kingdom

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: August 19, 2020
• First Posted: September 2, 2020
• Study Start: September 29, 2020
• Primary Completion: September 12, 2022
• Study Completion: December 2, 2022
• Last Updated: November 13, 2023
• Results First Posted: November 13, 2023

Record last verified: 2023-11

Locations

RU (17); GB (1); BU (5); US (39); DE (15); GR (4); PL (6); RO (9); SL (3); HU (6); KR (5); CZ (12)