A study to test whether different doses of BI 1291583 help people with bronchiectasis

JRCT ID: jRCT2041220074

Registered date:18/10/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: non-cystic fibrosis bronchiectasis (nCFB)
• Date of first enrollment: 11/10/2022
• Target sample size: 240
• Countries of recruitment: USA,Japan,Canada,Japan,Mexico,Japan,Belgium,Japan,Bulgaria,Japan,Czech Republic,Japan,Denmark,Japan,France,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,Israel,Japan,Itary,Japan,Netherlands,Japan,Poland,Japan,Portugal,Japan,Spain,Japan,Turkey,Japan,United Kingdom,Japan,Rep. of Korea,Japan,Australia,Japan,Latvia,Japan
• Study type: Interventional

Intervention(s)

Drug: BI 1291583 (1mg, 2.5mg, 5mg)
Other: Placebo
Route: oral

Outcome(s)

• Primary Outcome: Time to first pulmonary exacerbation up to 48 weeks after first drug administration (Time Frame: Up to week 48)

Secondary Outcome

1. Rate of pulmonary exacerbations (number of events per person-time) up to week 48 after first drug administration [ Time Frame: Up to week 48 ]
2. 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 ]
3. 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 ]
4. 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 ]
5. 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 ]
6. Occurrence of an exacerbation by week 24 after first drug administration [ Time Frame: Up to week 24 ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

1. Male or female patients: Women of childbearing potential (WOCBP) adhering to contraception requirements may be included as soon as regulatory criteria are fulfilled. At start of the trial this is only considered possible for WOCBP in the USA, Canada, Mexico and Turkey.
WOCBP and men able to father a child must be ready and able to use highly effective methods of birth control per International Council for Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly, preferably with low user dependency, and one barrier method in addition. A list of contraception methods meeting these criteria and instructions on the duration of their use are 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.
2.Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation.
3. Age of patients when signing the informed consent >=18 and =<85 years.
4. Clinical history consistent with bronchiectasis (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.
5. 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
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.
6. Current sputum producers with a history of chronic expectoration who are able to provide a spontaneous (not induced) sputum sample at Screening Visit 1.

Exclude criteria

1. 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).
2. Estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula < 30 mL/min at Visit 1.
3. An absolute blood neutrophil count <1000/mm3 at Visit 1 (equivalent to <1,000 cells/uL or <109 cells/L).
4. 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.
5. Positive serological tests for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection, or known infection status.
Concomitant diagnosis and therapy
6. A current diagnosis of:
- Cystic Fibrosis
- Hypogammaglobulinemia
- Common variable immunodeficiency
- alpha1-antitrypsin deficiency
- Allergic bronchopulmonary aspergillosis being treated or requiring treatment
- Tuberculosis or non tuberculous mycobacterial infection being treated or requiring treatment according to local guidelines
- Acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
- 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.
7. Acute respiratory infection or any other acute infection requiring systemic or inhaled therapy within 4 weeks prior Visit 1 and throughout screening.
8. 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.
9. Received any live attenuated vaccine within 4 weeks prior to Visit 2.
10. 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.
11. 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.

Related Information

• Primary Sponsor: Imazu Susumu
• Secondary ID(s): NCT05238675