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

  • STATUS
    Recruiting
  • days left to enroll
    23
  • participants needed
    800
  • sponsor
    Verona Pharma plc
Updated on 17 December 2021

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).

Details
Condition Chronic Obstructive Pulmonary Disease
Treatment Placebo, Ensifentrine
Clinical Study IdentifierNCT04542057
SponsorVerona Pharma plc
Last Modified on17 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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
Other Requirements for Inclusion
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
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
Randomization Criteria Criteria for Inclusion at Randomization
Capable of using the study nebulizer correctly and complying with all study
restrictions and procedures
Completion of the e-Diary at least 5 of the last 7 days of the Run-in period
Ability to perform acceptable spirometry in accordance with ATS/ERS guidelines
Symptoms of COPD: A score of ≥2 on the mMRC Dyspnea Scale

Exclusion Criteria

Current Condition or Medical History
COPD exacerbation requiring oral or parenteral steroids within 3 months of Screening
Previous lung resection or lung reduction surgery within 1-year of Screening
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
Lower respiratory tract infection within 6 weeks of Screening
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
Myocardial infarction or unstable angina within 6 months prior to Screening
Long term oxygen use defined as oxygen therapy prescribed for greater than 12 hours
Diagnosis of New York Heart Association Class III and Class IV heart failure
per day. As needed oxygen use (≤12 hours per day) is not exclusionary
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
Other respiratory disorders including, but not limited to, a current diagnosis of
Prior/Concomitant Therapy
asthma, active tuberculosis, lung cancer, sarcoidosis, lung fibrosis, interstitial
lung diseases, unstable sleep apnea, known alpha-1 antitrypsin deficiency, core
History or Suspicion of Drug or Alcohol Abuse
pulmonale, clinically significant pulmonary hypertension, clinically significant
bronchiectasis, or other active pulmonary diseases
Laboratory and Other Diagnostic Parameters
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
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
Unstable or life-threatening cardiac arrhythmia requiring intervention within 3
months prior to Screening
Other Exclusions
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
study
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
Use of prohibited medications within the time intervals
Current or history of past drug or alcohol abuse within the past 5 years
Glomerular Filtration Rate (eGFR) <30 mL/min. The Chronic Kidney Disease Epidemiology
Collaboration Creatinine (2009) calculation will be used
Criteria for Exclusion from Randomization
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
Positive COVID-19 result at Screening or between Screening and Randomization
is fractionated and direct bilirubin <35%)
Prohibited medication use between Screening Visit 0 and Visit 1
Hepatitis B antibody
Positive findings for both Hepatitis B surface antigen (HBsAg) and Hepatitis B
core antibody (anti-HBc) are excluded, as this indicates acute or chronic
infection
Negative findings for HBsAg and Hepatitis B surface antibody (anti-HBs) but
positive findings for anti-HBc are excluded as this may indicate current or
resolving infection
Positive findings for anti-HBc and anti-HBs but negative findings for HBsAg are
not excluded, as this indicates immunity due to natural infection
Positive findings for anti-HBs but negative findings for HBsAg and anti-HBc are
not excluded, as this indicates immunity due to hepatitis B vaccination
Hepatitis C antibody positive
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
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
trial 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 trial 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
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
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