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AzTrials

Chronic Obstructive Pulmonary DiseasePhase 3NCT04535986

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

A Phase 3 study testing Ensifentrine in people with Chronic Obstructive Pulmonary Disease, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 122 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Chronic Obstructive Pulmonary Disease
What is being tested?
Ensifentrine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
763 participants
Where
122 sitesin 12 countries
Study dates
29 Sep 2020to 2 Dec 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • Pre- and Post-albuterol/salbutamol FEV1/FVC ratio of <0.70.
  • Post-albuterol/salbutamol FEV1 ≥30 % and ≤70% of predicted normal calculated using the National Health and Nutrition Examination Survey III.
  • Maintenance Therapy: Patients on no maintenance/background therapy or patients on stable maintenance LAMA or LABA therapy are eligible. Patients taking maintenance LAMA or LABA therapy must demonstrate stable use of the maintenance LAMA or LABA therapy for at least 3 months prior to Screening and agree to continue use for the duration of the study. Background maintenance LAMA or LABA bronchodilator therapy will be capped at 50% of patients.
  • Other Requirements for Inclusion
  • Capable of withholding SABAs for 4 hours prior to initiation of any spirometry. Patients in the maintenance LAMA or LABA therapy stratum must be capable of withholding Twice-Daily maintenance LAMA or LABA for 24 hours and Once-Daily maintenance LAMA or LABA for 48 hours prior to initiation of any spirometry.
  • Capable of using the study nebulizer correctly and complying with all study restrictions and procedures.
  • Ability to perform acceptable spirometry in accordance with ATS/ERS guidelines.
  • Symptoms of COPD: A score of ≥2 on the mMRC Dyspnea Scale.
  • Completion of the e-Diary at least 5 of the last 7 days of the Run-in period.

Who cannot join

  • 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.
  • Long term oxygen use defined as oxygen therapy prescribed for greater than 12 hours per day. As needed oxygen use (≤12 hours per day) is not exclusionary.
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  • 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).
  • History of or current malignancy of any organ system, treated or untreated within the past 5 years, except for localized basal or squamous cell carcinoma of the skin.
  • Findings on physical examination that an investigator considers to be clinically significant at Screening.
  • Prior/Concomitant Therapy
  • Use of prohibited medications within the time intervals.
  • History or Suspicion of Drug or Alcohol Abuse
  • Current or history of past drug or alcohol abuse within the past 5 years.
  • Laboratory and Other Diagnostic Parameters
  • Glomerular Filtration Rate (eGFR) <30 mL/min. The Chronic Kidney Disease Epidemiology Collaboration Creatinine (2009) calculation will be used (Levey, 2009).
  • Alanine aminotransferase (ALT) ≥ 2 x upper limit of normal (ULN), alkaline phosphatase and/or bilirubin > 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Any other abnormal hematology, biochemistry, or viral serology deemed by an investigator to be clinically significantly abnormal. Abnormal chemistry and/or hematology may be repeated during Screening.
  • Chest X-ray (CXR; posterior-anterior) at Screening, or in the 12 months prior to Screening with clinically significant abnormalities not attributable to COPD. If a CXR within the past 12 months is not available but a computerized tomography (CT) scan within the same time period is available, the CT scan may be reviewed in place of a CXR. For subjects in Germany, if a CXR or CT scan is not available in the 12 months prior to Screening, the subject is not eligible for the study.
  • Electrocardiogram (ECG) finding that is significantly abnormal on the 12-lead ECG obtained at Screening.
  • Other Exclusions
  • Use of an experimental drug within 30 days or 5 half-lives of Screening, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical study within 30 days prior to Screening.
  • Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical study within 30 days prior to Screening.
  • Intolerance or hypersensitivity to albuterol/salbutamol or ensifentrine (RPL554) or any of its excipients/components.
  • Prior receipt of blinded study medication in an ensifentrine (RPL554) study.
  • Affiliation with the investigator site, including an Investigator, Sub-Investigator, study coordinator, study nurse, other employee of participating investigator or study site or a family member of the aforementioned.
  • Inability to read, understand, and/or complete questionnaires (in the opinion of the Investigator).
  • A disclosed history or one known to the Investigator of significant non-compliance in previous investigational studies or with prescribed medications.
  • Any other reason that the Investigator considers makes the patient unsuitable to participate.
  • COPD exacerbation or lower respiratory tract infection between Screening and Randomization (defined as use of any additional treatment other than current treatment and rescue medication and/or emergency department or hospital visit). Patients with a severe COPD exacerbation that requires hospitalization may not be rescreened.
  • Positive COVID-19 result at Screening or between Screening and Randomization.
  • Prohibited medication use between Screening Visit 0 and Visit 1.
  • Significantly abnormal ECG finding on the 12-lead ECG obtained at Screening as assessed by the investigator or site medical doctor/medically qualified person or on the pre-dose (prior to randomization) ECG obtained at Visit 1.
  • In the event that the central ECG reviewer discovers a significant ECG abnormality on the Visit 1 ECG, the patient will be discontinued.
  • Did not meet one or more of the Inclusion Criteria or met one or more of the Exclusion Criteria.

Trial locations and contacts

122 sites in 12 countries.

122 sites in 12 countries

United States39 sites

  • Pulmonary Research of Abingdon, LLC

    Abingdon, Virginia, 24210

  • John Hopkins University School of Medicine

    Baltimore, Maryland, 21224

  • Chattanooga Research & Medicine (CHARM)

    Chattanooga, Tennessee, 37404

  • Clinical Research of West Florida, Inc.

    Clearwater, Florida, 33765

  • St. Francis Medical Institute

    Clearwater, Florida, 33765

  • Medtrial

    Columbia, South Carolina, 29204

  • Remington Davis Clinical Research

    Columbus, Ohio, 43215

  • iResearch Atlanta, LLC

    Decatur, Georgia, 30030

  • Clinical Research Associates of Central PA, LLC

    DuBois, Pennsylvania, 15801

  • Pulmonary Research Institute of SE Michigan

    Farmington Hills, Michigan, 48336

  • Velocity Clinical Research - Grants Pass

    Grants Pass, Oregon, 97527

  • Qway Research, LLC

    Hialeah, Florida, 33010

  • West Houston Clinical Research Services

    Houston, Texas, 77055

  • Beach Physicians Medical Group

    Huntington Beach, California, 92647

  • MultiSpecialty Clinical Research, Inc.

    Johnson City, Tennessee, 37601

  • New Phase Research Development

    Knoxville, Tennessee, 37909

  • Multi-Specialty Research Associates, Inc.

    Lake City, Florida, 32055

  • MDFirst Research

    Lancaster, South Carolina, 29720

  • Sierra Clinical Research

    Las Vegas, Nevada, 89106

  • Alliance for Multispecialty Research, LLC

    Las Vegas, Nevada, 89119

  • Downtown LA Research Center, Inc.

    Los Angeles, California, 90017

  • Elite Clinical Research

    Miami, Florida, 33144

  • Global Research Solutions Corp

    Miami, Florida, 33144

  • Phoenix Medical Research

    Miami, Florida, 33165

  • Monroe Biomedical Research

    Monroe, North Carolina, 28112

  • IMA Clinical Research, LLC

    New York, New York, 10036

  • Florida Institute for Clinical Research

    Orlando, Florida, 32825

  • LinQ Research, LLC

    Pearland, Texas, 77584

  • Phoenix Medical Group

    Peoria, Arizona, 85381

  • University of Pittsburgh Physicians, Emphysema/COPD Research Center

    Pittsburgh, Pennsylvania, 15213

  • IACT Health

    Rincon, Georgia, 31326

  • Midwest Chest Consultants

    Saint Charles, Missouri, 63301

  • Sherman Clinical Research

    Sherman, Texas, 75092

  • The Clinical Research Center, LLC

    St Louis, Missouri, 63141

  • Precision Clinical Research

    Sunrise, Florida, 33351

  • In-Quest Medical Research, LLC

    Suwanee, Georgia, 30024

  • Clinical Research of West Florida, Inc.

    Tampa, Florida, 33606

  • AMR Tempe

    Tempe, Arizona, 85281

  • TPMG Clinical Research Williamsburg

    Williamsburg, Virginia, 23188

Other trials in United States

Russia17 sites

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

    Barnaul, 656038

  • SBHI "Regional Clinical Hospital #3"

    Chelyabinsk, 454091

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

    Kemerovo, 650002

  • LLC "Novosibirsk GastroCenter"

    Novosibirsk, 630007

  • SBIH of Novosibirsk Region "Clinical Emergency Hospital #2"

    Novosibirsk, 630008

  • City Clinical Hospital #25

    Novosibirsk, 630075

  • SPb SBHI "Vvedenskaya hospital"

    Saint Petersburg, 191180

  • "LEC at the LLC "LLC "Energiy Zdorovya"

    Saint Petersburg, 194156

  • LLC "Institute of Medical Examinations"

    Saint Petersburg, 196084

  • Research center Eco-safety, LLC

    Saint Petersburg, 196143

  • Pavlov First Saint Petersburg State Medical University

    Saint Petersburg, 197022

  • SPb SBIH "City Hospital # 40 of Kurortnyi region"

    Sestroretsk, 197706

  • SBHI of Yaroslavl Region "Clinical Hospital # 2"

    Yaroslavl, 1500030

  • SBHI of Yaroslavl Region "Clinical Hospital # 2"

    Yaroslavl, 150010

  • SBHI Outpatient 2

    Yaroslavl, 150047

  • LLC MA New Hospital

    Yekaterinburg, 620109

  • City Hospital #6

    Yekaterinburg, 620149

Other trials in Russia

Germany15 sites

  • Clinical Studies Pankow Dr Dr Evelin Liefring/Ishak Teber

    Berlin, Free Hanseatic City of Bremen, 13187

  • Studienpraxis Berlin-Brandenburg

    Berlin, 10119

  • Praxis an der Oper.

    Berlin, 10625

  • Zentrum fur Klinische Forschung

    Cologne, North Rhine-Westphalia, 51069

  • MECS GmbH Cottbus

    Cottbus, Brandenburg, 03050

  • Praxis Dr. Keller

    Frankfurt am Main, Hesse, 60389

  • IKF Pneumologie GmbH & Co. KG

    Frankfurt am Main, Hesse, 60596

  • PRI Pulmonary Research Institute, Pneumologisches Forschungsinstitut GmbH

    Großhansdorf, Schleswig-Holstein, 22927

  • Pneumologische Praxis Dr. Falk Brunner

    Leipzig, Saxony, 04157

  • Salvus-Klinische Studien GmbH.

    Leipzig, Saxony, 04207

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

    Lübeck, Schleswig-Holstein, 23552

  • SMO.MD GmbH

    Magdeburg, Saxony-Anhalt, 39120

  • Ballenberger, Freytag, Wenisch Institut für klinische Forschung

    Neu-Isenburg, 63263

  • Dr. Christian Schlenska

    Peine, Lower Saxony, 31224

  • Framol-med GmbH, Pneumologische Gemeinschaftspraxis Rheine

    Rheine, North Rhine-Westphalia, 48431

Other trials in Germany

Czechia12 sites

  • MUDr. I. Cierna Peterova s.r.o.

    Brandýs nad Labem, 25001

  • Fakultni nemocnice Brno, Dept of Klinika nemoci plicnich a tuberkulozy

    Brno, 625 00

  • EDUMED s.r.o.

    Broumov, 550 01

  • MUDr. Petr Pravda

    Hlučín, 74801

  • MediTrial s.r.o.

    Jindřichův Hradec, 377 01

  • Plicni ambulance Kralupy s.r.o.

    Kralupy nad Vltavou, 278 01

  • CEFISPIRO s.r.o.

    Lovosice, 41002

  • Odborná plicní ambulance Opava s.r.o.

    Opava, 74601

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

    Prague, 149 00

  • Plicni centrum s.r.o.

    Prague, 15300

  • MUDr. Josef Veverka, Plicni ambulacne

    Rokycany, 33701

  • Plicni stredisko Teplice s.r.o.

    Teplice, 41501

Other trials in Czechia

Romania9 sites

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

    Brasov, 500091

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

    Brasov, 500283

  • Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca

    Brasov, 500366

  • Quantum Medical Center S.R.L.

    Bucharest, 012071

  • Institutul de Pneumoftiziologie "Marius Nasta"

    Bucharest, 050159

  • S.C Cardiomed S.R.L

    Cluj-Napoca, 400371

  • Impatiens SRL

    Codlea, 505100

  • Fundatia Cardioprevent

    Timișoara, 300134

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

    Timișoara, 300310

Other trials in Romania

Hungary6 sites

  • Clinexpert Kft.

    Budapest, 1033

  • Szalay János Rendelőintézet Tüdőgyógyászati Szakrendelés

    Hajdúnánás, 4080

  • Bajcsy-Zsilinszky Kórház és Rendelőintézet Monori Rendelőintézete

    Monor, 2200

  • Karolina Kórház-Rendelőintézet, Tüdőgyógyászat

    Mosonmagyaróvár, 9200

  • Püspökladányi Egészségügyi Szolgáltató Nonprofit Kft.

    Püspökladány, 4150

  • Markusovszky Egyetemi Oktatókórház Tüdőgondozó

    Szombathely, 9700

Other trials in Hungary

Poland6 sites

  • NZOZ Centrum Medyczne KERmed

    Bydgoszcz, 85-231

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, 80-214

  • Centrum Alergologii Sp. z o. o.

    Lublin, 20-552

  • ETG Siedlce

    Siedlce, 08-110

  • NASZ LEKARZ Ośrodek Badań Klinicznych

    Torun, 87-100

  • ETG Warszawa

    Warsaw, 02-793

Other trials in Poland

Bulgaria5 sites

  • SHATPPD - Haskovo, EOOD

    Haskovo, 6300

  • Medical center Medconsult Pleven OOD

    Pleven, 5800

  • UMHAT-Plovdiv AD

    Plovdiv, 4003

  • Medical Center Hera EOOD

    Sofia, 1510

  • MC "Sv. Ivan Rilski", OOD

    Vidin, 3700

Other trials in Bulgaria

South Korea5 sites

  • Yeungnam University Hospital

    Daegu, 42415

  • Kyung Hee University Hospital

    Seoul, 02447

  • Asan Medical Center

    Seoul, 05505

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

    Seoul, 06591

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

    Seoul, 07345

Other trials in South Korea

Greece4 sites

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

    Athens, 11527

  • University General Hospital of Heraklion, Pulmonary Clinic

    Heraklion, 71110

  • University General Hospital of Ioannina, University Respiratory Clinic

    Ioannina, 45500

  • University General Hospital of Larissa, University Pulmonary Clinic

    Larissa, 41110

Other trials in Greece

Slovakia3 sites

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

    Bardejov, 08501

  • Inspiro, s.r.o.

    Humenné, 06601

  • Plucna ambulancia Hrebenar, s.r.o.

    Spišská Nová Ves, 05201

Other trials in Slovakia

United Kingdom1 site

  • Respiratory Clinical Trials Ltd

    London, Greater London, W1T6AH

Other trials in United Kingdom

About this study

Official title: A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ensifentrine Over 24 Weeks (With a 48-week Safety Subset) in Subjects With Moderate to Severe COPD

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).

Being tested
Ensifentrine, Placebo
Keywords
COPD
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnsifentrineDrug

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

  • PlaceboDrug

    Dosage Formulation: Ensifentrine Placebo Nebulizer solution Frequency: Twice Daily for 24 weeks or 48 weeks

Study groups in NCT04535986
Study groupRoleWhat they receive
Arm 1ExperimentalEnsifentrine Nebulized Suspension; 3 mg BID
Receives: Drug: Ensifentrine
Arm 2Placebo comparatorPlacebo Nebulized BID
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline (pre-dose on Day 1) and Week 12

Secondary outcomes (9)

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

    Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Peak FEV1 is the maximum value in the 4 hours after dosing. 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 ATS/ERS guidelines.

    Measured: Baseline (pre-dose on Day 1), post-dose on Day 1, Weeks 6, 12, and 24

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

    The E-RS scale consists of 11 questions, with 3 sub-domains of: breathlessness, cough and sputum, and chest symptoms. The E-RS sub-domain score was calculated as the sum from the relevant questions. The E-RS total score was derived as the sum of the raw scores of the 11 items ranging from 0 to 40. Higher scores indicates severe respiratory symptoms. Scores were derived weekly as the mean over 7 days prior to the visit, using only days where data was recorded. The E-RS was collected daily by electronic diary (e-diary). Baseline is the mean over the 7 days prior to the first intake of study medication, using only days where data was recorded.

    Measured: Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24

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

    The SGRQ questionnaire consists of 17 questions, split into 2 parts. Part 1 consisted of the first 8 questions and was related to the symptoms subdomain. The remaining 9 questions were in Part 2, which were related to the activity and impacts subdomains. The total score was calculated by dividing the summed weights by the maximum possible weight for all items in the questionnaire and expressing the result as a percentage. Score ranging from 0 to 100 and higher scores indicated a worse outcome. Baseline is the score calculated on Day 1 prior to 4 hour post-dose spirometry.

    Measured: Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24

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

    Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Morning trough FEV1 was the last value collected prior to the morning dose. Baseline FEV1 is the mean of the two 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 ATS/ERS guidelines.

    Measured: Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24

  5. 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

    Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Average FEV1 AUC0-4h was defined as area under the curve over 4 hours of the FEV1, divided by 4 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 ATS/ERS guidelines.

    Measured: Baseline (pre-dose on Day 1), post-dose on Day 1, Weeks 6, 12, and 24

  6. Percentage of SGRQ Responders at Weeks 6, 12 and 24

    The SGRQ questionnaire consists of 17 questions, split into 2 parts. Part 1 consisted of the first 8 questions and was related to the symptoms subdomain. The remaining 9 questions were in Part 2, which were related to the activity and impacts subdomains. The total score was calculated by dividing the summed weights by the maximum possible weight for all items in the questionnaire and expressing the result as a percentage. Responder was a patient with an improvement from baseline in SGRQ total score of 4 or more. Percentage of SGRQ responders are reported.

    Measured: Weeks 6, 12 and 24

  7. LS Mean Change From Baseline to the Mean Weekly Rescue Medication Use at Weeks 6, 12 and 24

    Use of rescue medication (albuterol/salbutamol) per week was calculated as the LS mean use daily over 7 days. Daily rescue medication use was collected in an e-diary throughout the study. Baseline is the mean over the 7 days prior to the first intake of study medication, calculated as the sum of puffs taken, divided by number of days data has been recorded.

    Measured: Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24

  8. LS Mean Transition Dyspnea Index (TDI) Questionnaire Total Score at Weeks 6, 12 and 24

    The TDI is a questionnaire that focused on 3 sub-domains: functional impairment, magnitude of task and magnitude of effort. Sub-domain score was calculated as the sum from the related questions. Total score was calculated as the sum of the sub-domain scores. The TDI measures the change in dyspnea severity from the baseline as measured by the baseline dyspnea index. It was rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement). Higher scores indicate better outcome. Change from baseline was assessed with the Baseline Dyspnea Index.

    Measured: Weeks 6, 12 and 24

  9. LS Mean Change From Baseline FEV1 to Evening Trough FEV1 at Week 12

    Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Evening trough FEV1 was the value collected at 12 hours post-morning dose and prior to the evening dose. 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 ATS/ERS guidelines.

    Measured: Baseline (pre-dose on Day 1) and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Sep 2020
  2. Study start29 Sep 2020
  3. Primary completion12 Sep 2022
  4. Study completion2 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
763 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04535986
Sponsor's protocol ID
RPL554-CO-301
Status last verified
Nov 2023
First submitted
19 Aug 2020
Last updated
13 Nov 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 39854278

  • 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.

    PubMed 39197510

  • 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.

    PubMed 39106052

  • 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.

    PubMed 37364283

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ensifentrine in people with Chronic Obstructive Pulmonary Disease, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 122 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 122 sites in United States, Russia, Germany, Czechia, Romania and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Baseline (pre-dose on Day 1) and Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04535986, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2023.

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