A Study to Test Whether Different Doses of BI 1291583 Help People With Bronchiectasis

• ClinicalTrials.gov Identifier: NCT05238675
• Recruitment Status: Active, not recruiting
• First Posted: February 14, 2022
• Last Update Posted: April 30, 2024
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: February 3, 2022
• First Posted Date: February 14, 2022
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: March 21, 2022
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 3, 2022): Time to first pulmonary exacerbation up to 48 weeks after first drug administration [ Time Frame: Up to week 48 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 15, 2022)

• Key secondary: Rate of pulmonary exacerbations (number of events per person-time) up to week 48 after first drug administration [ Time Frame: Up to week 48 ]
• Absolute change from baseline in Quality of Life Questionnaire - Bronchiectasis (QOLB) respiratory symptoms domain score at week 24 after first drug administration [ Time Frame: At baseline and at week 24 ]
• Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 12 after first drug administration [ Time Frame: At baseline and at week 12 ]
• Absolute change from baseline in St. George's Respiratory Questionnaire (SGRQ) Symptoms score at week 24 after first drug administration [ Time Frame: At baseline and at week 24 ]
• Absolute change from baseline in percent predicted post-bronchodilator forced expiratory volume in one second (FEV1%pred) at week 24 after first drug administration [ Time Frame: At baseline and at week 24 ]
• Occurrence of an exacerbation by week 24 after first drug administration [ Time Frame: Up to week 24 ]

Original Secondary Outcome Measures (submitted: February 3, 2022)

• Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 12 after first drug administration [ Time Frame: At baseline and at week 12 ]
• Rate of pulmonary exacerbations (number of events per person-time) up to week 48 after first drug administration [ Time Frame: Up to week 48 ]
• Absolute change from baseline in St. George's Respiratory Questionnaire (SGRQ) Symptoms score at week 24 after first drug administration [ Time Frame: At baseline and at week 24 ]
• Absolute change from baseline in percent predicted post-bronchodilator forced expiratory volume in one second (FEV1%pred) at week 24 after first drug administration [ Time Frame: At baseline and at week 24 ]
• Occurrence of an exacerbation by week 24 after first drug administration [ Time Frame: Up to week 24 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Test Whether Different Doses of BI 1291583 Help People With Bronchiectasis
• Official Title: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Dose-finding Study Evaluating Efficacy, Safety and Tolerability of BI 1291583 qd Over at Least 24 Weeks in Patients With Bronchiectasis (AirleafTM)

Brief Summary

This study is open to adults with bronchiectasis. People can join the study if they produce sputum and have a history of flare-ups (also called exacerbations).

The purpose of this study is to find out whether a medicine called BI 1291583 helps people with bronchiectasis.

Participants are put into 4 groups randomly, which means by chance. Participants in groups 1, 2, and 3 get different doses of BI 1291583. Participants in group 4 get placebo. Placebo tablets look like BI 1291583 tablets, but do not contain any medicine. Participants take the tablets once a day.

Participants are in the study for between 6 months and 1 year. During this time, they visit the study site about 10 times and get about 5 phone calls from the site staff.

The doctors document when participants experience flare-ups during the study. The time to the first flare-ups is compared between the treatment groups. Doctors also regularly check participants' health and take note of any unwanted effects.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Bronchiectasis

Intervention

• Drug: BI 1291583
  BI 1291583
• Drug: Placebo
  Placebo

Study Arms

• Experimental: BI 1291583: Low dose group
  Intervention: Drug: BI 1291583
• Experimental: BI 1291583: Medium dose group
  Intervention: Drug: BI 1291583
• Experimental: BI 1291583: High dose group
  Intervention: Drug: BI 1291583
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 23, 2023): 322
• Original Estimated Enrollment (submitted: February 3, 2022): 240
• Estimated Study Completion Date: May 29, 2024
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

- Male or female patients: Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly, as well as one barrier method. A list of contraception methods meeting these criteria is provided in the patient information.

Men participating in this clinical trial must use male contraception (condom or sexual abstinence) if their sexual partner is a WOCBP.

• Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation.
• Age of patients when signing the informed consent ≥18 (for Korea: ≥19) and ≤85 years.
• Clinical history consistent with bronchiectasis (e.g., cough, chronic sputum production and/or recurrent respiratory infections) and investigator confirmed diagnosis of bronchiectasis by computed tomography (CT) scan. Subjects whose past chest radiographic image records are not available will undergo a chest CT scan during Screening. Historical scans must not be older than 5 years.

• History of pulmonary exacerbations requiring antibiotic treatment. In the 12 months before Visit 1, patients must have had either:

  • at least 2 exacerbations, or
  • at least 1 exacerbation and a St. George´s Respiratory Questionnaire (SGRQ) Symptoms score of >40 at screening visit 1.

For patients on stable oral or inhaled antibiotics as chronic treatment for bronchiectasis, at least one exacerbation must have occurred since initiation of stable antibiotics.

- Current sputum producers with a history of chronic expectoration who are able to provide a spontaneous (not induced) sputum sample at Screening Visit 1.

Exclusion Criteria:

Laboratory and medical examination

• Aspartate Aminotransferase (AST) and / or Alanine Aminotransferase (ALT) >3.0 x upper limit of normal (ULN) at Visit 1, or moderate or severe liver disease (defined by Child-Pugh score B or C hepatic impairment).
• Estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula < 30 mL/min at Visit 1.
• An absolute blood neutrophil count <1,000/mm^3 at Visit 1 (equivalent to <1,000 cells/µL or <109 cells/L).
• Any findings in the medical examination and/or laboratory value assessed at Screening Visit 1 or during screening period, that in the opinion of the investigator may put the patient at risk by participating in the trial.
• Positive serological tests for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection, or known infection status.

Concomitant diagnosis and therapy

• A current diagnosis of:

  • Cystic Fibrosis
  • Hypogammaglobulinemia
  • Common variable immunodeficiency
  • α1-antitrypsin deficiency being treated with augmentation therapy
  • Allergic bronchopulmonary aspergillosis being treated or requiring treatment
  • Tuberculosis or non-tuberculous mycobacterial infection being treated or requiring treatment according to local guidelines
  • Palmoplantar keratosis; or keratoderma climactericum
  • Hypothyroidism, myxedema, chronic lymphedema with associated hyperkeratosis of the skin, acrocyanosis. If a subject has hypothyroidism but is treated and compensated, the subject is allowed into the trial
  • Psoriasis affecting palms and soles; or body surface area for psoriasis ≥ 10%
  • Reactive arthritis (Reiter's syndrome); keratoderma blennorrhagicum
  • Pityriasis rubra pilaris
  • Atopic dermatitis affecting palms and soles; or body surface area for atopic dermatitis ≥ 10%
  • Active extensive verruca vulgaris, as per investigator's discretion
  • Active fungal infection of hand and/or feet not adequately treated, or not responsive to antifungal therapy, as per investigator's discretion.
• Any clinically relevant (at the discretion of the investigator) acute respiratory infection within 4 weeks prior Visit 2, or any other acute infection requiring systemic or inhaled anti-infective therapy within 4 weeks prior Visit 2.
• Any evidence of a concomitant disease, such as Papillon-Lefevre Syndrome, relevant pulmonary, gastrointestinal, hepatic, renal, cardiovascular, metabolic, immunological, hormonal disorders, or patients who are immunocompromised with a higher risk of invasive pneumococcal disease or other invasive opportunistic infections (such as histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis), that in the opinion of the investigator, may put the patient at risk by participating in the study.
• Received any live attenuated vaccine within 4 weeks prior to Visit 2.

• Medical conditions associated with periodontal disease (to be evaluated by a periodontist or dentist):

  • Any tooth that can potentially cause pain or infection as noted in the oral exam unless they are corrected before the study (e.g. pulp necrosis).
  • Severe periodontal disease defined as with pocket depth measurements ≥ 6 mm on 2 or more teeth.
  • Class-3 mobility or Class-3 furcation involvement.
  • Scheduled tooth extraction during the study period.
• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.

Further exclusion criteria apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Latvia, Mexico, Netherlands, Poland, Portugal, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05238675
• Other Study ID Numbers: 1397-0012; 2021-003304-41 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link http://trials.boehringeringelheim.com/ to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• URL: https://www.mystudywindow.com/msw/datasharing

• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: April 2024