The primary objective of the trial is to assess a non-flat dose-response curve and to evaluate the dose-response relationship for 3 oral dose regimens of BI 1291583 versus placebo, on the primary endpoint, time to first pulmonary exacerbation up to…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the time to first pulmonary exacerbation up to 48 weeks
after first drug adminstration.
Secondary outcome
The key secondary endpoint is the rate of pulmonary exacerbations (number of
events per person-time) up to week 48 after first drug administration.
secondary endpoints:
1) Absolute change from baseline in Quality of Life Questionnaire -
Bronchiectasis (QOL-B) respiratory symptoms domain score at week 24 after first
drug administration
2) Relative change from baseline in neutrophil elastase (NE) activity in sputum
at week 12 after first drug administration
3) Absolute change from baseline in St. George's Respiratory Questionnaire
(SGRQ) Symptoms score at week 24 after first drug administration
4) Absolute change from baseline in percent predicted postbronchodilator forced
expiratory volume in one second (FEV1%pred) at week 24 after first drug
administration
5) Occurrence of an exacerbation by week 24
Background summary
Bronchiectasis is a heterogenous respiratory syndrome characterised by abnormal
and irreversible dilated bronchioles. Patients with bronchiectasis can have a
variety of symptoms which include persistent cough, production of large volumes
of sputum, dyspnea, chronic fatigue and hemoptysis. These symptoms are
burdensome and are often associated with social stigmatism, urine incontinence,
anxiety, depression and a reduced quality of life.
Bronchiectasis is characterised by neutrophilic bronchial inflammation. Serine
proteases released by neutrophils, such as neutrophil elastase, cause
structural damage to the airways, mucus gland hyperplasia, impaired mucus
clearance, and result in a vicious cycle of recurrent severe infections and
further airway damage.
There is a high unmet medical need for efficacious anti-inflammatory treatments
to ameliorate neutrophilic bronchial inflammation. This dose finding trial will
investigate BI 1291583 in patients with bronchiectasis to evaluate efficacy,
safety and tolerability over at least 24 weeks and up to 48 weeks.
Also refer to protocol sections 1.1 (medical background) and 1.3 (rationale for
performing the trial).
Study objective
The primary objective of the trial is to assess a non-flat dose-response curve
and to evaluate the dose-response relationship for 3 oral dose regimens of BI
1291583 versus placebo, on the primary endpoint, time to first pulmonary
exacerbation up to 48 weeks.
Study design
This is a multi-center, randomised, placebo-controlled, double-blind, parallel
group clinical trial to investigate the efficacy, safety and tolerability of
three different doses of BI 1291583 (orally, qd).
Approximately 240 eligible patients will be randomised in a 2:1:1:2 ratio to
one of the treatment groups.
Also refer to protocol section 3.1.
Intervention
24 to 48 weeks of treatment with BI 1291538 (orally, qd).
- Placebo qd (n = 80)
- BI 1291583 1 mg qd (n = 40)
- BI 1291583 2.5 mg qd (n = 40)
- BI 1291583 5 mg qd (n = 80)
Also refer to protocol section 4.1.
Study burden and risks
Burden:
Study subjects will visit the hospital more often compared to regular care.
Additionally, the visits are likely to take more time. Study visits can be
experienced as intensive and time-consuming. During the visits, additional
tests are performed, including Pulmonary Function Tests, and blood is drawn.
All assessments are summarized in the protocol flowchart (p. 5-7).
Risks:
The risks relating to specific study procedures are summarized in protocol
table 1.4.2.
The clinical data of BI 1291583 showed an acceptable safety profile in healthy
volunteers. No clinical data of BI 1291583 in patients are available to date. A
Phase II trial with another CatC inhibitor, brensocatib, showed that 24 weeks
treatment resulted in a slightly increased occurrence of periodontal disease
and skin exfoliation. No elevated risk of infection was reported in previous
clinical studies with other inhibitors of CatC or with inhibitors of NE.
Also refer to protocol section 1.4.
Basisweg 10
Amsterdam 1043 AP
NL
Basisweg 10
Amsterdam 1043 AP
NL
Listed location countries
Age
Inclusion criteria
- Male or female patients
- Age of patients when signing the informed consent >=18 and <=85 years.
- 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.
- 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 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
Exclusion criteria
- AST and / or ALT >3.0 x 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 CKD-EPI formula <30
mL/min at Visit 1.
- An absolute blood neutrophil count <1,000/mm3 at Visit 1.
- 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.
- A current diagnosis of
-- Cystic Fibrosis
-- Hypogammaglobulinemia
-- Common variable immunodeficiency
-- α1-antitrypsin deficiency 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 [Laboratory tests (e.g.
Quantiferon Gold test) may be performed at the discretion of the investigator]
-- 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 (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, or 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).
- 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 criteria apply.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-003304-41-NL |
| ClinicalTrials.gov | NCT05238675 |
| CCMO | NL79730.100.21 |