A study to test how well BI 1291583 is tolerated by people with cystic fibrosis bronchiectasis (ClairaflyTM)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH, Boehringer Ingelheim Espana S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

23 Feb 2024 → 8 Oct 2024

Decision date (initial)

2023-11-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacodynamic, Pharmacokinetic

The primary objective is to estimate the number and percentage of patients who has at least one treatment-emergent AE (TEAE) during the trial.

Secondary objectives 2

1. The secondary objective is to estimate the PD effect at week 8 after the first drug administration.
2. The other secondary objective is to estimate the PK effect after the first dose and at steady state after multiple dosing of BI 1291583.

Conditions and MedDRA coding

cystic fibrosis bronchiectasis

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age of patients when signing the informed consent ≥18 years.
2. Historical clinical diagnosis of CF (symptoms of CF and sweat chloride ≥ 60 mmol/L and/or 2 CF-causing CFTR mutations).
3. Investigator-confirmed diagnosis of BE by CT scan and clinical history consistent with BE (e.g., cough, chronic sputum production, recurrent respiratory infections). Subjects whose past chest CT records are not available will undergo a chest CT scan during Screening. Historical scans must not be older than 5 years.
4. History of pulmonary exacerbations requiring antibiotic treatment. In the 12 months before Visit 1, patients must have had either: a. at least 2 exacerbations, or b. at least 1 exacerbation and an SGRQ Symptoms score of >40 at screening visit 1 For patients on stable oral or inhaled antibiotics as chronic treatment for BE, at least one exacerbation must have occurred while on stable antibiotics.
5. Patients must be able to provide spontaneous or induced sputum samples.
6. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
7. "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. Men participating in this clinical trial must use male contraception (condom or sexual abstinence) if their sexual partner is a WOCBP."

Exclusion criteria 6

1. 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.
2. Estimated glomerular filtration rate (eGFR) according to CKD-EPI formula < 30 mL/min at Visit 1.
3. Absolute blood neutrophil count < 1,000/mm3 (equivalent to < 1000 cells/μL or < 109 cells/L) at Visit 1.
4. Any findings in the medical examination (including BP, PR, or ECG) and/or laboratory value assessed at Visit 1 or during screening period that in the opinion of the investigator may put the patient at risk by participating in the trial [Laboratory parameters from Visit 1 have to satisfy the laboratory threshold values as shown above. Visit 2 laboratory results will be available only after randomisation. In case at Visit 2 the results do no longer satisfy the entry criteria, the investigator has to decide whether it is justified that the patient remains in the trial. The justification for decision needs to be documented].
5. Positive serological tests for hepatitis B, hepatitis C (also confirmed with HCV RNA), or human immunodeficiency virus (HIV) infection, or known infection status.
6. Further criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of TEAEs up to 16 weeks from first drug administration.

Secondary endpoints 5

1. Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 8 after first drug administration (8 weeks was chosen as timepoint for this secondary endpoint to synchronise with potential cycling antibiotic use)
2. AUC over a dosing interval (AUCτ) for the first dose.
3. Maximum concentration (Cmax) for the first dose.
4. AUCτ at steady state (AUCτ,ss).
5. Cmax at steady state (Cmax,ss).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Boehringer Ingelheim Espana S.A.

Sponsor organisation

Boehringer Ingelheim Espana S.A.

Address

Carrer Prat De La Riba 50, Sant Cugat Del Valles Sant Cugat Del Valles

City

Barcelona

Postcode

08174

Country

Spain

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Sponsor responsibilities

Article 77 compliance

Boehringer Ingelheim International GmbH

Contact point sponsor

Boehringer Ingelheim International GmbH

Article 77 implementation

Boehringer Ingelheim International GmbH

Locations

6 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 115 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications