ENSIFENTRINE for Non-Cystic Fibrosis Bronchiectasis

Inclusion criteria

• {"criterion_text":"- 1. 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 inform consent form (ICF) and in this protocol.\n- 10. Willing and able to attend all study visits and adhere to all study assessments and procedures.\n- 2. Age: Subject must be 18 to 85 years of age, inclusive, at the time of signing the ICF.\n- 3. Sex: • Males are eligible to participate if they agree to use contraception as described in the contraceptive guidance (Appendix 7) from signing the ICF, 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 1 of the following conditions apply: a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 7. OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 7 from signing the ICF, throughout the study, and for at least 30 days after the last dose of blinded study medication.\n- 4. Clinical history consistent with bronchiectasis (cough, chronic sputum production, and/or recurrent respiratory infections) confirmed by chest CT demonstrating bronchiectasis affecting 1 or more lobes. Confirmation may be based on prior chest CT within 5 years prior to signing the ICF; subjects whose past CT image records are not available will require chest CT scan during screening. Note: If a subject has no clinical history consistent with bronchiectasis, they may not be re-screened.\n- 5. Current sputum producer with a history of chronic expectoration and able to provide sputum sample at the clinic during screening. Note: If a subject is unable to produce sputum spontaneously during the Screening Period, the subject is considered a screen failure and may be re-screened only once with Medical Monitor approval .\n- 6. Sputum color at screening of mucopurulent or purulent as assessed by the sputum color chart (Murray et al. 2009).\n- 7. ≥ 1 documented pulmonary exacerbation defined by an antibiotic prescription by a physician for the signs and symptoms of respiratory infections in the past 12 months prior to signing the ICF. Note: The number of subjects randomized with exactly 1 documented pulmonary exacerbation in the past 12 months prior to signing the ICF will be capped at approximately 30% for the entire study population.\n- 8. Capable of using the study nebulizer correctly.\n- 9. Ability to perform acceptable spirometry in accordance with American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (Graham et al. 2019). Note: Subjects who need to repeat spirometry because they did not meet the acceptability criteria will be allowed to repeat the test up to 2 times without being rescreened."}

Exclusion criteria

• {"criterion_text":"- 1. Either: a. A diagnosis of COPD OR b. A primary diagnosis of asthma, as judged by the PI.\n- 10. Initiated or altered therapy with ICS within 4 weeks prior to Visit 2.\n- 11. Unable to withhold short-acting beta-agonists or short-acting muscarinic antagonists for ≥ 4 hours prior to spirometry.\n- 12. Significant hemoptysis within 6 weeks prior to Visit 2.\n- 13. Currently participating in or scheduled to participate in an intensive pulmonary rehabilitation program.\n- 14. Current or chronic history of clinically significant, unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, or known hepatic or biliary abnormalities except for Gilbert syndrome or asymptomatic gallstones.\n- 15. History of or current malignancy of any organ system, treated or untreated within the 5 years prior to signing the ICF, except for localized basal or squamous cell carcinoma of the skin.\n- 16. Current diagnosis or history of severe depression or suicidal ideation or other significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the PI.\n- 17. Subject has clinically significant findings on physical examination that may increase the risk associated with study participation, study treatment administration, or may interfere with the interpretation of study results, and in judgement of the PI would make the subject inappropriate for entry into this study.\n- 18. eGFR < 30 mL/min .\n- 19. Screening ALT ≥ 2 × ULN, AST ≥ 2 × ULN, alkaline phosphatase and/or bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if fractionated bilirubin < 35%).\n- 2. Bronchiectasis due to cystic fibrosis, hypogammaglobulinemia common variable immunodeficiency, severe immunodeficiency, or requirement for treatment with intravenous immunoglobulin.\n- 20. Any other abnormal hematology, biochemistry, or viral serology deemed by the PI to be clinically significant. Abnormal chemistry and/or hematology may be repeated during the Screening Period.\n- 21. ECG finding that is significantly abnormal as defined in Appendix 4 on a 12-lead ECG obtained during the Screening Period.\n- 22. Participation in any other interventional, clinical studies within 3 months before Day 1, or 5 half-lives, whichever is longer.\n- 23. Intolerance of or hypersensitivity to ensifentrine or any of its excipients/components.\n- 24. Current or history of drug or alcohol abuse within the 5 years prior to signing the ICF.\n- 25. Affiliation with the PI site, including an PI, Sub-PI, study coordinator, study nurse, other employee of participating PI or study site or a family member of the aforementioned.\n- 3. Current smoker defined as by the CDC.\n- 4. Former cigarette smokers with a history of cigarette smoking ≥ 10 pack years at Screening. Pipe and/or cigar use cannot be used to calculate pack-year history.\n- 5. A diagnosis of primary ciliary dyskinesia.\n- 6. Current treatment for nontuberculous mycobacterial lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis.\n- 7. Presence of acute exacerbation or another acute infection that required antibiotic treatment within 4 weeks of signing the ICF (or within 12 weeks of signing the ICF if the antibiotic prescription is a macrolide).\n- 8. Use of the following prohibited medications within the designated time periods: a. Immunomodulatory agents within 3 months prior to signing the ICF.b. CFTR modulators within 1 week prior to signing the ICF.c. Treated with doses of cyclic antibiotics 90 days prior to signing the ICF.d. Theophylline and PDE4 inhibitors within 48 hours prior to signing the ICF.e. Brensocatib within 3 months or 5 half-lives, whichever is longer, prior to signing the ICF.f. Ohtuvayre at any time prior signing the ICF.\n- 9. Initiated or altered therapy with oral or inhaled antibiotics as chronic treatment for NCFBE within 90 days prior to signing the ICF."}

Primary endpoints

• {"endpoint_text":"- Rate of protocol-defined pulmonary exacerbations over the study interval (number of events per subject-year).","definition_or_measurement_approach":"Number of protocol-defined pulmonary exacerbation events per subject-year (as stated: \"(number of events per subject-year)\")."}

Secondary endpoints

• {"endpoint_text":"- Time to the onset of the first protocol-defined pulmonary exacerbation over the study interval. Mean change from Baseline at Week 24 in: ­ E-RS Cough and Sputum Domain, ­ SGRQ, QOL-B Respiratory Symptoms Domain, ­ CAAT, ­ Percent of the predicted FEV1, Mean change from Baseline at Weeks 6 and 12 in: ­ E-RS Cough and Sputum Domain, SGRQ, ­ QOL-B Respiratory Symptoms Domain, CAAT, ­ Percent of the predicted FEV1 (Wk 12 only) Mean change from Baseline at Weeks 6, 12, and 24 in: ­QOL-B total score","definition_or_measurement_approach":"Includes time-to-event (time to first protocol-defined pulmonary exacerbation) and mean change from baseline at specified visits (Weeks 6, 12, 24) for patient-reported outcomes (E-RS Cough and Sputum Domain, SGRQ, QOL-B Respiratory Symptoms Domain, CAAT) and lung function (percent predicted FEV1) as stated in the endpoint description."}

Italy

Earliest CTIS Part Ii Submission Date

06-11-2024

Latest Decision Or Authorization Date

14-07-2025

Processing Time Days

250

Number Of Sites

5

Number Of Participants

35

Spain

Earliest CTIS Part Ii Submission Date

06-11-2024

Latest Decision Or Authorization Date

16-07-2025

Processing Time Days

252

Number Of Sites

8

Number Of Participants

35

Primary sponsor

Full Name

Verona Pharma PLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

PPD Development LP

Responsibilities

sponsorDuties codes: 1,10,11,12,13,2,3,5,6,7,8 (broad operational responsibilities as listed in record)

Name

Eresearchtechnology Inc.

Responsibilities

Questionnaires and Subject eDiaries

Name

Bioclinica Inc.

Responsibilities

HRCT (High resolution computed tomography)

Name

Fisher Clinical Services GmbH / Fisher Clinical Services Inc.

Responsibilities

Importation, QP release, storage and distribution of IMP; IP packaging and labelling

Name

4g Clinical LLC

Responsibilities

Operational support (sponsorDuties code: 3)

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"United Biosource LLC","duties_or_roles":"sponsorDuties codes: 8 (contact email: VeronaSafety@ubc.com)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement in Spain","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"University Of Dundee(The)","duties_or_roles":"Bronchoscopy sub-study samples analysis; code 4","organisation_type":"Educational Institution"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Central Lab;PK sample analysis; code 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Questionnaires and Subject eDiaries","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Importation, QP release, storage and distribution of IMP","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: 1,10,11,12,13,2,3,5,6,7,8 (multiple operational responsibilities listed)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"IP packaging and labelling","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"HRCT (High resolution computed tomography)","organisation_type":"Laboratory/Research/Testing facility"}