A Phase II Study of Ensifentrine in Non-Cystic Fibrosis Bronchiectasis

Официальное название

A Phase II, Randomized, Double-Blind, Placebo- Controlled Study of Ensifentrine in Subjects With Non-Cystic Fibrosis Bronchiectasis

Обзор

This study is a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of ensifentrine inhalation suspension (3 mg) delivered twice daily via standard jet nebulizer up to 52 weeks, compared to placebo, in participants with non-cystic fibrosis bronchiectasis (NCFBE).

Подробное описание

The primary objective of this study is to assess the effect of ensifentrine vs placebo in addition to standard of care on pulmonary exacerbations, symptoms and quality of life in participants with NCFBE.

Participants will be treated for up to 52 weeks (some subjects may end earlier as the sponsor may end the study after the last subject in the study completes the Week 24 visit).

Participants will be randomized to receive either ensifentrine suspension or placebo via standard jet nebulizer during the treatment period and neither participants nor study staff will know which a participant is receiving.

Вмешательства

• Препарат Nebulized Ensifentrine Suspension; 3 mg
  Administered by a standard jet nebulizer, twice daily up to a maximum of 52 weeks
• Препарат Nebulized Placebo Solution
  Administered by a standard jet nebulizer, twice daily up to a maximum of 52 weeks

Первичные конечные точки

• Rate of protocol-defined pulmonary exacerbations (number of events per subject-year) [Срок оценки: Through study completion (up to 52 weeks)]

Вторичные конечные точки (11)

• Time to the onset of the first protocol-defined pulmonary exacerbation [Срок оценки: Through study completion (up to 52 weeks)]
• Change from Baseline in Evaluating Respiratory Symptoms (E-RS) Cough and Sputum Domain score [Срок оценки: Baseline, Week 6, Week 12, and Week 24]
• Change from Baseline in Saint George's Respiratory Questionnaire (SGRQ) total score [Срок оценки: Baseline, Week 6, Week 12, and Week 24]
• Change from Baseline in quality of life - bronchiectasis questionnaire (QOL-B) Respiratory Symptoms Domain score [Срок оценки: Baseline, Week 6, Week 12, and Week 24]
• Change from Baseline in Chronic Airways Assessment Test (CAAT) total score [Срок оценки: Baseline, Week 6, Week 12, and Week 24]
• Change from Baseline in Percent of the predicted forced expiratory volume over 1 second (FEV1) [Срок оценки: Baseline, Week 12, and Week 24]
• Change from Baseline of forced vital capacity (FVC) [Срок оценки: Baseline, Week 12, and Week 24]
• Incidence of Adverse Events [Срок оценки: Through study completion (approximately 52 weeks)]
• PK Sub-study only: Ensifentrine area under the curve from time 0 to 12 hours (AUC 0 -12) [Срок оценки: Week 12, Week 18, and Week 24]
• PK Sub-study only: Ensifentrine maximum plasma drug concentration (Cmax) [Срок оценки: Week 12, Week 18, and Week 24]
• Pharmacokinetic (PK) Sub-study only: Ensifentrine time to Cmax (tmax) post morning dose [Срок оценки: Week 12, Week 18, and Week 24]

Критерии участия

Критерии включения

• 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 1 of the following conditions apply:

• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance from Screening throughout the study and for at least 30 days after the last dose of blinded study medication
• 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 the prior 5 years; subjects whose past CT image records are not available will require chest CT scan during screening Notes: If a subject has no clinical history consistent with bronchiectasis, they may not be re-screened
• Current sputum producer with a history of chronic expectoration and able to provide sputum sample spontaneously at the clinic during screening
• ≥ 1 documented pulmonary exacerbation defined by an antimicrobial prescription (i.e., antibiotic or antiviral) by a physician for the signs and symptoms of respiratory infections in the past 12 months before screening
• Capable of using the study nebulizer correctly
• Ability to perform acceptable spirometry in accordance with American Thoracic Society and European Respiratory Society guidelines as assessed by the Investigator

Критерии исключения

• A diagnosis of COPD or a primary diagnosis of asthma, as judged by the investigator
• Bronchiectasis due to cystic fibrosis, primary hypogammaglobulinemia common variable immunodeficiency, severe immunodeficiency, or requirement for treatment with intravenous immunoglobulin
• Current smoker defined as by the Centers for Disease Control and Prevention (CDC)
• Meets both of the following

• Former cigarette smokers with a history of cigarette smoking ≥ 10 pack years at Screening \[number of pack years = (number of cigarettes per day / 20) × number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. 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 Screening AND
• Evidence within 1 year prior to randomization of obstructed lung function as shown by forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of < 0.70
• A diagnosis of primary ciliary dyskinesia (PCD) is not exclusionary. Subjects with a diagnosis of PCD are permitted to be enrolled, but the proportion of subjects with PCD enrolled in the study may be limited
• Current treatment for nontuberculous mycobacterial lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis
• Presence of acute exacerbation or acute infection that required acute treatment within 28 days of randomization
• Use of the following prohibited medications within the designated time periods:

• Chronic, systemic immunomodulatory agents for any chronic indication (including but not limited to the following: methotrexate, systemic corticosteroids, see adalimumab, azathioprine, dupilumab, cyclosporine, hydroxychloroquine, etc.) within 90 days prior to signing the ICF
• CFTR modulators (e.g., ivacaftor, lumacaftor, tezacaftor) within 1 week prior to signing the ICF
• Theophylline and oral PDE4 inhibitors (e.g., roflumilast, apremilast, crisaborole) within 48 hours prior to signing the ICF
• Ohtuvayre at any time prior to signing the ICF
• Initiated or altered therapy within 90 days prior to randomization with:

• oral or inhaled antibiotics as chronic treatment (including macrolides)
• Cyclic antibiotics: defined as prescribed regular cycles of on antibiotic treatment and off antibiotic treatment (for example, but not limited to, 28 days on an antibiotic and 28 days off an antibiotic). Note: Subjects on cyclic antibiotics must be actively taking antibiotics for at least 7 days prior to randomization through the day of randomization
• Dipeptidyl peptidase 1 (DPP1) or cathepsin C (CatC) inhibitor (e.g., brensocatib)
• Initiated or altered therapy with ICS within 4 weeks prior to randomization
• Unable to withhold short-acting beta-agonists or short-acting muscarinic antagonists for ≥ 4 hours prior to spirometry
• Significant hemoptysis (≥ 300 mL or requiring blood transfusion) within 6 weeks prior to randomization
• Currently participating in or scheduled to participate in an intensive pulmonary rehabilitation program (a maintenance rehabilitation program is allowed if their schedule and procedure will be consistent for the duration of the study)
• Current or chronic history of 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 Note: Chronic stable hepatitis B and C is not exclusionary if the subject otherwise meets study entry criteria
• 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
• Estimated glomerular filtration rate (eGFR) < 30 mL/min
• Alanine aminotransferase (ALT) ≥ 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≥ 2 × ULN, alkaline phosphatase and/or bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable only in subjects with a diagnosis of Gilbert's syndrome)
• Participation in any other interventional, clinical studies (drugs or devices) within 30 days, or 5 half-lives, whichever is longer, prior to signing the ICF
• Intolerance of or hypersensitivity to ensifentrine or any of its excipients/components
• Current or history of drug or alcohol abuse within the past 5 years
• Significantly abnormal ECG finding

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 29 центров

• Kirklin Clinic of UAB Hospital — Birmingham
• So Cal Institute for Respiratory Diseases, Inc. — Los Angeles
• University of California Davis Medical Center — Sacramento
• National Jewish Health Main Campus — Denver
• MedStar Georgetown University Hospital — Washington D.C.
• University of Miami — Miami
• Emory University at Saint Joseph Pulmonary Clinic — Atlanta
• Augusta University — Augusta
• … и ещё 21 центр

Великобритания · 9 центров

• Ninewells Hospital - PPDS — Dundee
• Queen Elizabeth University Hospital - PPDS — Glasgow
• Birmingham Heartlands Hospital — Birmingham
• Queens Hospital Belfast — Belfast
• Royal Papworth Hospital — Cambridge
• Royal Infirmary of Edinburgh - PPDS — Edinburgh
• Liverpool Heart and Chest Hospital - PPDS — Liverpool
• Royal Brompton Hospital — London
• … и ещё 1 центр

Испания · 8 центров

• Hospital Universitario A Coruña — A Coruña
• Hospital del Mar — Barcelona
• Hospital Clinic de Barcelona — Barcelona
• Hospital Universitario Vall d'Hebron - PPDS — Barcelona
• Hospital Universitario de Bellvitge — Barcelona
• Hospital General Universitario Gregorio Marañon — Madrid
• Hospital Universitario La Paz - PPDS — Madrid
• Hospital Universitario Quironsalud Madrid — Madrid

Италия · 5 центров

• IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna
• Fondazione IRCCS San Gerardo dei Tintori — Monza
• Istituto Clinico Humanitas — Rozzano
• Fondazione IRCCS Policlinico San Matteo — Pavia
• AOU Policlinico Gaspare Rodolico-San Marco Presidio Ospedaliero Gaspare Rodolico — Catania

Идентификаторы

NCT: NCT06559150 · RPL554-NCFB-220 · 2024-514845-12

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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