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

  • STATUS
    Recruiting
  • End date
    Aug 28, 2022
  • participants needed
    800
  • sponsor
    Verona Pharma plc
Updated on 28 November 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 Lung Disease, COPD (Chronic Obstructive Pulmonary Disease), chronic obstructive pulmonary disease (copd), COPD, chronic obstructive pulmonary disease
Treatment Placebo, Ensifentrine
Clinical Study IdentifierNCT04535986
SponsorVerona Pharma plc
Last Modified on28 November 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) 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
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
Inclusion Criteria at Randomization (RPL554-CO-301)
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

Exclusion Criteria

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
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
)
\. 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%)
\. 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. 20. Hepatitis C antibody positive. 21. 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. 22. 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. 23. 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
Exclusion Criteria at Randomization (RPL554-CO-301)
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
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