Evaluation of Long-Term Safety and Efficacy of BI 1291583 in Patients with Bronchiectasis: A Randomized, Double-Blind, Parallel Group, Roll-Over Study
- Trial ID
- 2023-503290-38-00
- Protocol
- 1397-0017
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** of BI 1291583 in patients with **bronchiectasis** by assessing the absolute number and the percentage of patients experiencing treatment-emergent adverse events (TEAEs) throughout the trial. This is clinically relevant as it provides critical information on the safety profile of the medication, which is essential for determining its suitability for long-term use in managing bronchiectasis.
Secondary objectives include:
- Assessing the impact of BI 1291583 in prolonging the time to the first pulmonary exacerbation. This is important for understanding the potential of the drug to delay the worsening of respiratory symptoms, thereby improving patient outcomes.
- Evaluating the impact of BI 1291583 in reducing the rate of pulmonary exacerbation events. This objective aims to determine the drug's effectiveness in decreasing the frequency of exacerbations, which can lead to better disease management and quality of life for patients.
Participants
The clinical trial involves a total of **112 participants** diagnosed with **bronchiectasis**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on their completion of the treatment period in a prior Phase II trial, specifically trials 1397-0012 or 1397-0013, as per the protocol. The trial includes individuals who are part of a vulnerable population, and both genders are represented. Women of childbearing potential are required to adhere to stringent contraceptive measures to ensure a low failure rate. All participants provided signed and dated written informed consent in compliance with Good Clinical Practice and local legislation. The trial does not specify particular lifestyle considerations such as diet or physical activity.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the long-term safety and efficacy of oral doses of BI 1291583 in patients with **bronchiectasis**. The trial is a roll-over study, meaning it includes participants who have completed a previous Phase II trial with the same investigational product. The primary objective is to assess the safety by monitoring the occurrence of treatment-emergent adverse events (TEAEs) throughout the trial. Secondary endpoints include the time to first pulmonary exacerbation and the rate of pulmonary exacerbations over the course of the study.
The trial is expected to last until March 2026, with recruitment having started in June 2023. Participants will be involved in the study for a maximum treatment period of 12 months. The study involves several key visits: an inclusion (screening) visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to conclude participation. The inclusion criteria require participants to have completed a previous trial with BI 1291583, be male or female with women of childbearing potential using effective contraception, and provide informed consent. There are no specific exclusion criteria listed.
Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The investigational product, BI 1291583, is administered orally in tablet form, with doses of 1 mg, 2.5 mg, and 5 mg being evaluated. Placebo tablets matching these doses are also used to maintain the double-blind design. An auxiliary medication, **salbutamol sulfate**, is provided for inhalation use as needed. The trial is conducted in accordance with Good Clinical Practice (GCP) and local regulations, ensuring the safety and rights of participants are prioritized throughout the study.
Treatment
The clinical trial involves the administration of **BI 1291583**, an investigational medication, in three different dosages: 1 mg, 2.5 mg, and 5 mg. **BI 1291583** is formulated as a tablet and is administered orally. The maximum daily doses for the 1 mg, 2.5 mg, and 5 mg formulations are 1 mg, 2.5 mg, and 5 mg, respectively. The total maximum dose over the treatment period is 365 mg for the 1 mg dosage, 912.5 mg for the 2.5 mg dosage, and 1825 mg for the 5 mg dosage. The treatment period extends up to 12 months. **BI 1291583** is of chemical origin and is not a paediatric formulation. Participant compliance is monitored throughout the trial to ensure adherence to the dosing schedule.
In addition to the experimental medication, the trial includes the use of **placebo** tablets that match the appearance of the **BI 1291583** tablets in 1 mg, 2.5 mg, and 5 mg dosages. These placebos are used to maintain the double-blind nature of the study. The placebo tablets are administered orally with the same frequency and duration as the corresponding **BI 1291583** dosages.
**Salbutamol sulfate** is included as an auxiliary treatment in the trial. It is administered as a pressurised inhalation suspension for inhalation use. The maximum daily dose of **salbutamol sulfate** is 400 micrograms, with a total maximum dose of 2800 micrograms over the 12-month treatment period. An actuator device is used to facilitate the administration of the inhalation suspension. **Salbutamol sulfate** is of chemical origin and is not a paediatric formulation.
Efficacy
The efficacy of the clinical trial will be assessed through several key endpoints. The primary endpoint focuses on the **occurrence of treatment-emergent adverse events (TEAEs)** throughout the trial duration. Secondary endpoints include the time to the first pulmonary exacerbation from the initial drug administration to the trial's conclusion, as well as the rate of pulmonary exacerbations, measured as the number of events per person-time over the course of the trial. These endpoints will provide comprehensive insights into the efficacy of the treatment in patients with bronchiectasis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients who completed treatment period in Phase II trial (1397-0012 or 1397-0013) as planned per protocol.
- 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.
- Signed and dated written informed consent prior to admission to the trial, in accordance with Good Clinical Practice (GCP) and local legislation.
Exclusion Criteria
- Moderate or severe liver disease (defined by Child-Pugh score B or C hepatic impairment) or AST and/or ALT >3.0x ULN at Visit 1 (or at the last safety assessment in the parent trial, if no more than 6 weeks passed since then).
- Estimated glomerular filtration rate (eGFR) according to CKD-EPI formula <30 mL/min at Visit 1. (or at the last safety assessment in the parent trial, if no more than 6 weeks passed since then).
- An absolute blood neutrophil count <1,000/mm3 (equivalent to <1,000 cells/μL or <109 cells/L) at Visit 1 (or at the last safety assessment in the parent trial, if no more than 6 weeks passed since then).
- Any findings in the medical examination and/or laboratory value assessed at Visit 1 (or at the last safety assessment in the parent trial, concerning the lab tests, if no more than 6 weeks passed since then)., that in the opinion of the investigator may put the patient at risk by participating in the trial.
- A new diagnosis of: • Hypogammaglobulinemia • Common variable immunodeficiency • α1-antitrypsin deficiency being treated 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 and responsive to antifungal therapy, as per investigator’s discretion
- Any clinically relevant respiratory infection within 4 weeks prior Visit 2 - unless recovered in the opinion of the investigator by Visit 2
- Any acute infection requiring systemic or inhaled anti-infective therapy within 4 weeks prior Visit 2
- Positive serological tests for hepatitis B, hepatitis C (also confirmed with HCV RNA), or human immunodeficiency virus (HIV) infection, or known infection status at Visit 2.
- Any new evidence of a concomitant disease, such as PLS, 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 trial.
- Received any live attenuated vaccine within 4 weeks prior to Visit 1.
- Medical conditions associated with severe periodontal disease (to be evaluated by a periodontist or dentist) at Visit 1: • Any tooth that can potentially cause pain or infection as noted in the oral exam unless they are corrected before Visit 2 (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
- Patients who must or wish to continue the intake of restricted medications (Table 6) or any drug considered likely to interfere with the safe conduct of the trial.
- Further exclusion criteria apply.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 10 Jun 2023 | 4 |
 Bulgaria | Not Recruiting | 10 Jun 2023 | 6 |
 Czechia | Not Recruiting | 10 Jun 2023 | 2 |
 Denmark | Not Recruiting | 10 Jun 2023 | 7 |
 France | Not Recruiting | 10 Jun 2023 | 10 |
 Germany | Not Recruiting | 10 Jun 2023 | 24 |
 Greece | Not Recruiting | 10 Jun 2023 | 4 |
 Hungary | Not Recruiting | 10 Jun 2023 | 4 |
 Italy | Not Recruiting | 10 Jun 2023 | 8 |
 Latvia | Not Recruiting | 10 Jun 2023 | 19 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
SALBUTAMOL SULFATE | Other | — | INHALATION USE | 400 | 12 | SUB04303MIG |
Placebo matching to BI 1291583 1 mg | Placebo | N/A | — | — | — | N/A |
Placebo matching to BI 1291583 5 mg | Placebo | N/A | — | — | — | N/A |
BI 1291583 2.5 mg | Test | TABLET | ORAL USE | 2.5 | 12 | PRD10212211 |
BI 1291583 1 mg | Test | TABLET | ORAL USE | 1 | 12 | PRD10211733 |
BI 1291583 5 mg | Test | TABLET | ORAL USE | 5 | 12 | PRD10211734 |
Placebo matching to BI 1291583 2.5 mg | Placebo | N/A | — | — | — | N/A |