TerminatedNCT04656275Updated Nov 27, 2024Results posted

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

A Phase 1 interventional study of BI 1323495 and Placebo in Non-cystic Fibrosis Bronchiectasis, sponsored by Boehringer Ingelheim. Terminated at 3 sites in Germany. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-11-27.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Why this study was terminated

Company decision

Phase: Phase 1
Study type: Interventional
Enrollment: 7
Allocation: Randomized
Ages: 18 Years to 80 Years
Sex: All

Study 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.

Conditions studied

Non-cystic Fibrosis Bronchiectasis

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In context

Bronchiectasis

369 studies on the registry are indexed under Bronchiectasis; 105 are open to participants now.

This study's enrollment of 7 is below the median of 60 across 233 interventional studies indexed under Bronchiectasis.

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Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 80 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 7 participants (actual)

Study arms

Experimental
BI 1323495 treatment group (part 1)
Part 1
Drug: BI 1323495
Experimental
BI 1323495 treatment group (part 2)
Part 2
Drug: BI 1323495
Placebo comparator
Placebo group
Placebo
Drug: Placebo

Interventions

DrugBI 1323495
BI 1323495
DrugPlacebo
Placebo

What researchers measure

Primary outcomes

Number of Subjects With Drug-related Adverse Events (AEs)
Number of participants with drug-related adverse events (AEs) is presented. Participants with treatment-emergent drug-related Adverse Events (AEs) is reported.
Time frame: 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

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
The 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 is reported. The baseline value was calculated as the mean of the baseline values (at day -6, -2, day 1 predose). RFU is the standard output of a florescence reader. RFU (ex 360 nm, em460 nm).
Time frame: 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.
Change From Baseline to Week 12 (at Week 2, Week 4, Week 8, Week 12) in Neutrophil Cell Count in Sputum
The change from baseline to week 12 (at Week 2, Week 4, Week 8, Week 12) in absolute neutrophil cell count in sputum is reported. The baseline value was calculated as the mean of the baseline values (at day -6, -2, day 1 predose). RFU: Relative fluorescence unit
Time frame: 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.
Change From Baseline to Week 12 in Neutrophil Elastase (NE) Activity in Whole Blood After Stimulation With Zymosan (Normalized to Neutrophil Counts)
The change of NE activity from baseline to Day 15, Day 29, Day 57, Day 78, Day 82 and Day 98 in whole blood after stimulation with zymosan (normalized to neutrophil counts) is reported. Relative fluorescence unit (RFU) is the standard output of a florescence reader. RFU (ex 360 nm, em460 nm).
Time frame: 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.
Change From Baseline to Week 12 in Absolute Post-bronchodilator Forced Expiratory Volume in One Second, FEV1
The change from baseline to week 12 (at Week 2, Week 8, Week 12) in absolute post-bronchodilator forced expiratory volume in one second (FEV1).
Time frame: At baseline Day -2 before the first dose and at at Week 2, Week 8, Week 12 during treatment.

Results

Posted Nov 5, 2024

Limitations and caveats

The Part B of the study was not started due to the same reason that caused discontinuation of Part A, i.e. due to the need to clarify findings in nonclinical toxicity testing in animals.

Participant flow

This was a randomised, double blind, placebo-controlled, parallel group design, to compare safety and tolerability of different doses of BI 1323495 with placebo and to assess pharmacodynamics of BI 1323495 in sputum and in blood as well as early signs of clinical efficacy of BI 1323495 in patients with non-cystic fibrosis bronchiectasis (nCFB).

Participant flow — Overall Study
Milestone	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid
Started	2	5
Completed	0	1
Not completed	2	4
Withdrew: Study terminated by sponsor	2	4

Outcome measures

PrimaryNumber of Subjects With Drug-related Adverse Events (AEs)

Number of participants with drug-related adverse events (AEs) is presented. Participants with treatment-emergent drug-related Adverse Events (AEs) is reported.

Time frame:: 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.
Reported as:: Count of participants · Participants

Number of Subjects With Drug-related Adverse Events (AEs)
Participants	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid
Number of Subjects With Drug-related Adverse Events (AEs)	0	2

SecondaryChange From Baseline to Day 15, Day 29, Day 57, Day 78, Day 82 and Day 98 in Absolute Neutrophil Elastase (NE) Activity in Sputum

The 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 is reported. The baseline value was calculated as the mean of the baseline values (at day -6, -2, day 1 predose). RFU is the standard output of a florescence reader. RFU (ex 360 nm, em460 nm).

Time frame:: 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.
Reported as:: Mean · Relative fluorescence unit (RFU)

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
Relative fluorescence unit (RFU)	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid
Change from baseline to Day 15	3301.0	-156.9 ± 2028.5
Change from baseline to Day 29	2745.0	-194.4 ± 660.6
Change from baseline to Day 57	—	-497.1 ± 217.9
Change from baseline to Day 78	1665.0	—
Change from baseline to Day 82	—	383.0
Change from baseline to Day 98	—	582.3 ± 1257.7

SecondaryChange From Baseline to Week 12 (at Week 2, Week 4, Week 8, Week 12) in Neutrophil Cell Count in Sputum

The change from baseline to week 12 (at Week 2, Week 4, Week 8, Week 12) in absolute neutrophil cell count in sputum is reported. The baseline value was calculated as the mean of the baseline values (at day -6, -2, day 1 predose). RFU: Relative fluorescence unit

Time frame:: 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.
Reported as:: Mean · Neutrophils*10^9/Liter

Change From Baseline to Week 12 (at Week 2, Week 4, Week 8, Week 12) in Neutrophil Cell Count in Sputum
Neutrophils*10^9/Liter	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid
Time-matched change from baseline to Week 2	-9.7	27.1 ± 82.9
Time-matched change from baseline to Week 4	16.8	-7.8 ± 11.3
Time-matched change from baseline to Week 8	—	9.7 ± 23.4
Time-matched change from baseline to Week 12	-47.7	69.5

SecondaryChange From Baseline to Week 12 in Neutrophil Elastase (NE) Activity in Whole Blood After Stimulation With Zymosan (Normalized to Neutrophil Counts)

The change of NE activity from baseline to Day 15, Day 29, Day 57, Day 78, Day 82 and Day 98 in whole blood after stimulation with zymosan (normalized to neutrophil counts) is reported. Relative fluorescence unit (RFU) is the standard output of a florescence reader. RFU (ex 360 nm, em460 nm).

Time frame:: 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.
Reported as:: Mean · RFU/(10^9 cells/L)

Change From Baseline to Week 12 in Neutrophil Elastase (NE) Activity in Whole Blood After Stimulation With Zymosan (Normalized to Neutrophil Counts)
RFU/(10^9 cells/L)	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid
Time-matched change from baseline to Day 15	95.8	-7733.9 ± 2153.2
Time-matched change from baseline to Day 29 / -2:30	99.2	-6306.0 ± 852.6
Time-matched change from baseline to Day 29 / 6:00	238.1	-6649.6 ± 1505.1
Time-matched change from baseline to Day 57	-630.3	-5889.9 ± 786.0
Time-matched change from baseline to Day 82	-622.6 ± 1089.0	-5689.9 ± 3610.3
Time-matched change from baseline to Day 98	-326.4 ± 1295.0	1221.1 ± 2703.8

SecondaryChange From Baseline to Week 12 in Absolute Post-bronchodilator Forced Expiratory Volume in One Second, FEV1

The change from baseline to week 12 (at Week 2, Week 8, Week 12) in absolute post-bronchodilator forced expiratory volume in one second (FEV1).

Time frame:: At baseline Day -2 before the first dose and at at Week 2, Week 8, Week 12 during treatment.
Reported as:: Mean · Milliliter (mL)

Change From Baseline to Week 12 in Absolute Post-bronchodilator Forced Expiratory Volume in One Second, FEV1
Milliliter (mL)	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid
Time-matched change from baseline to Week 2	38 ± 113.1	1.4 ± 78.6
Time-matched change from baseline to Week 8	-27.0	1.0 ± 220.1
Time-matched change from baseline to Week 12	-138.0	-40.0 ± 178.2

Adverse events

Collected over From drug administration until 12:00 AM on day after last administration of study drug + 7 days (REP) or 12:00 AM on day after last contact date, which ever occurs first. Up to 13 weeks. All-cause mortality: Up to 13 weeks.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part A: Placebo Bid	0/2 (0%)	0/2 (0%)	0/2 (0%)
Part A: 30 mg BI 1323495 Bid	0/5 (0%)	0/5 (0%)	2/5 (40%)

Most frequent other events

Most frequent other events
Event	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid
BradycardiaCardiac disorders	0/2	1/5
PruritusSkin and subcutaneous tissue disorders	0/2	1/5

Baseline characteristics

Treated set (TS): The treated set included all patients who were randomised and received at least one dose of study drug. The treatment assignment was determined based on the first actual treatment the patients received. The TS was used for safety analyses and evaluation of biomarker and clinical assessments.

Age, Continuous
Age, Continuous(Years)	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid	Total
Mean	52.0 ± 8.5	59.2 ± 5.3	57.1 ± 6.6

Sex: Female, Male
Sex: Female, Male(Participants)	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid	Total
Female	0	3	3
Male	2	2	4

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid	Total
Hispanic or Latino	0	0	0
Not Hispanic or Latino	2	5	7
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	2	5	7
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Absolute neutrophil elastase (NE) activity in sputum
Absolute neutrophil elastase (NE) activity in sputum(Relative fluorescence unit (RFU))	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid	Total
Mean	19115.0 ± 598.2	15610.4 ± 9991.7	16778.6 ± 7952.8

Neutrophil cell count in sputum
Neutrophil cell count in sputum(Neutrophils*10^9/Liter)	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid	Total
Mean	338.9 ± 40.7	322.0 ± 123.9	327.6 ± 98.0

NE activity in whole blood after stimulation with zymosan, normalized to neutrophil counts
NE activity in whole blood after stimulation with zymosan, normalized to neutrophil counts(RFU/(10^9 cells/L))	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid	Total
Mean	5354.8 ± 3506.7	7278.5 ± 2574.4	6728.9 ± 2710.9

Absolute post-bronchodilator forced expiratory volume in one second, FEV1
Absolute post-bronchodilator forced expiratory volume in one second, FEV1(Milliliter (mL))	Part A: Placebo Bid	Part A: 30 mg BI 1323495 Bid	Total
Mean	3052.5 ± 475.9	2177.2 ± 434.5	2427.3 ± 588.3

Study locations

3 sites

IKF Pneumologie GmbH & Co. KG
Frankfurt, 60596, Germany
Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
Großhansdorf, 22927, Germany
KLB Gesundheitsforschung Lübeck GmbH
Lübeck, 23552, Germany

References and documents

Study documents

Study protocol · Apr 22, 2021
Statistical analysis plan · Sep 15, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 27, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04656275
Lead sponsor: Boehringer Ingelheim
Responsible party: Sponsor
First posted: Dec 7, 2020
Start date: Mar 4, 2021
Primary completion: Dec 20, 2021
Completion: Jan 19, 2022
Results posted: Nov 5, 2024
Last update: Nov 27, 2024

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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