Clinical trial NCT04656275: A Study in Patients With Non-cystic Fibrosis Bronchiectasis to Test How Well Different Doses of BI 1323495 Are Tolerated and How BI 1323495 Affects Biomarkers of Inflammation
Official title: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Different Oral Doses of BI 1323495 Bid Versus Placebo in Patients With Non-cystic Fibrosis Bronchiectasis (Randomised, Double-blind, Placebo-controlled, Parallel Group Trial)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-cystic Fibrosis Bronchiectasis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2020-12-07
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is open to adults with non-cystic fibrosis bronchiectasis. The main purpose of this study is to find out how a medicine called BI 1323495 is tolerated by people with non-cystic bronchiectasis.

The study tests 2 different doses of BI 1323495. Some of the participants get placebo. It is decided by chance who gets BI 1323495 and who gets placebo. Participants take BI 1323495 or placebo as tablets twice a day for 3 months. Placebo tablets look like BI 1323495 tablets but do not contain any medicine. Participants can also continue taking standard medicines for noncystic bronchiectasis throughout the study.

Participants are in the study for about 4 months. During this time, the participants visit the study site about 11 times and get about 2 phone calls. At the visits, doctors check the health of the participants and note any health problems that could have been caused by BI 1323495.


Eligibility criteria: Inclusion Criteria:

* 18 years to 80 years (inclusive) at the time of informed consent signature, male and female (not of childbearing potential) subjects

  --For 'female not of childbearing potential' at least one of the following criteria must be fulfilled:
  * Permanently sterile (permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy; tubal ligation is not a method of permanent sterilisation)
  * Postmenopausal, defined as at least 1 year of spontaneous amenorrhea without an alternative medical cause (in questionable cases a blood sample with Follicle Stimulating Hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory).
  * Men must be vasectomised with documented absence of sperm or use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after the last administration of trial medication if their sexual partner is a woman of childbearing potential (WOCBP)
* Clinical history consistent with non cystic fibrosis bronchiectasis (nCFB) (cough, chronic sputum production and/or recurrent respiratory infections) and proven and documented diagnosis of bronchiectasis by computed tomography (CT) scan including dilated airways compatible with bronchiectasis at initial diagnosis. Bronchiectasis of various etiologies will be allowed, with exclusion criteria as below.
* Vaccination against Streptococcus pneumoniae in accordance with national vaccination recommendations
* Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation.
* FEV1 ≥ 30 % predicted (post-bronchodilator) at Screening Visit 1.
* Stable (i.e., no dose change) regimen of standard nCFB treatment (including - but not limited to - hypertonic inhalation solutions, mucolytics, Long Acting Muscarinic Agonists (LAMA)/ Long Acting Beta Agonists (LABA) / inhaled corticosteriods (iCS), oral antibiotic maintenance regimen, and physiotherapy), if applicable, administered at least for 4 weeks prior to Screening Visit 1 and throughout the run-in period.
* Regular daily sputum producers with a history of chronic expectoration who are able to provide a typical bronchiectasis sputum sample at Screening Visit 1.
* Sputum neutrophil elastase positive based on point of care test (NEATstik® score ≥ 6) assessment at Visit 2a and Visit 2b.
* Subjects genotyped as UDP-Glucuronosyltransferase-2B17 (UGT2B17) extensive metabolizers prior to randomisation, i.e., carrying at least one functional allele of the UGT2B17 gene (\*1/\*1 or \*1/\*2)

Exclusion Criteria:

* Any finding in the medical examination (including BP, pulse rate (PR), or ECG) and/or laboratory value and/or any evidence of a concomitant disease assessed as clinically relevant by the investigator.
* Concomitant diagnosis of pulmonary disease other than bronchiectasis, chronic obstructive pulmonary disease (COPD), or asthma.
* A current diagnosis of cystic fibrosis (CF), primary immunodeficiency, active Allergic Bronchopulmonary Aspergillosis (ABPA) (defined by receipt of corticosteroids, anti-fungal treatment or monoclonal antibody treatment), or alpha-1 antitrypsin (A1AT) deficiency as underlying disease.
* A history or current immunodeficiency or are currently being treated (or are planned to be treated) with immunomodulatory drugs (except for iCS or low-dose oral corticosteroids), including disease-modifying anti-rheumatic drugs (DMARDs), and/or Immunglobulin G (IgG) treatments. Other medication that is excluded will be provided in the investigator site file (ISF). On the day of the site visit with lung function measurement, no bronchodilators should be used until after completion of lung function assessment
* Any acute infections defined as infections requiring antibiotic therapy, or Upper Respiratory Tract Infection (URTI). Are currently being treated (or are planned to be treated) for a nontuberculous mycobacterial (NTM) lung infection or tuberculosis.
* A history of invasive pneumococcal disease.
* Inhaled antibiotic treatment or cycling oral antibiotic treatment with changed dose regimen 4 weeks prior to Screening Visit 1.
* A treatment for a pulmonary exacerbation 4 weeks prior to Screening Visit 1.
* Laboratory confirmed severe acute respiratory syndrome (SARS)-coronavisurs (CoV)-2 infection (PCR positive) within 4 weeks prior to Screening Visit 1.
* Household contact with an individual with confirmed SARS-CoV-2 infection within 4 weeks prior to Screening Visit 1.
* Further exclusion criteria apply

Primary outcomes:
measure: Number of Subjects With Drug-related Adverse Events (AEs)
timeFrame: From drug administration until 12:00 AM on day after last administration of study drug + 7 days residual effect period (REP) or 12:00 AM on day after last contact date, which ever occurs first. Up to 13 weeks.
Secondary outcomes:
measure: Change From Baseline to Day 15, Day 29, Day 57, Day 78, Day 82 and Day 98 in Absolute Neutrophil Elastase (NE) Activity in Sputum
timeFrame: At baseline Day -6, Day -2, Day 1 before the first dose and at Day 15, Day 29, Day 57, Day 78, Day 82 and Day 98.
measure: Change From Baseline to Week 12 (at Week 2, Week 4, Week 8, Week 12) in Neutrophil Cell Count in Sputum
timeFrame: At baseline Day -6, Day -2, Day 1 before the first dose and at at Week 2, Week 4, Week 8, Week 12 during treatment.
measure: Change From Baseline to Week 12 in Neutrophil Elastase (NE) Activity in Whole Blood After Stimulation With Zymosan (Normalized to Neutrophil Counts)
timeFrame: At baseline Day 1, 2.5 hours (hrs) before the first dose and at Day 15, Day 29, Day 57, Day 78, Day 82 and Day 98.
measure: Change From Baseline to Week 12 in Absolute Post-bronchodilator Forced Expiratory Volume in One Second, FEV1
timeFrame: At baseline Day -2 before the first dose and at at Week 2, Week 8, Week 12 during treatment.
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: IKF Pneumologie GmbH & Co. KG
city: Großhansdorf
country: Germany
facility: Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
city: Lübeck
country: Germany
facility: KLB Gesundheitsforschung Lübeck GmbH
Study officials:
References: