A 4-week Study to Test Different Doses of BI 1265162 in Adolescents and Adults With Cystic Fibrosis Using the Respimat® Inhaler - BALANCE - CF™1

NCT04059094 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 1399-00032019-000261-21
• Study Type: interventional
• Target: 52
• Locations: 8 countries
• Sites: 26

Brief Summary

The primary objective of this trial is to assess the efficacy, safety and pharmacokinetics of twice daily inhaled doses of BI 1265162 delivered by Respimat® inhaler versus placebo in adolescents and adult patients with cystic fibrosis.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment

  Trough FEV1 was measured within 30 minutes prior to dosing of study medication.

  At 30 minutes prior to dosing in Day 1 (baseline) and Day 29 (end of 4-week treatment period).

Secondary Outcomes (9)

• Change From Baseline in Lung Clearance Index (LCI) Assessed by N2 Multiple Breath Washout (N2MBW) Procedure After 4 Weeks of Treatment

  At pre-dose in Day 1 (baseline) and Day 29 (end of 4-week treatment period).

• Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment

  At Day 1 (baseline) and Day 29 (end of 4-week treatment period).

• Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment

  At Day 1 (baseline) and Day 29 (end of 4-week treatment period).

• Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36

  From Day 1 (baseline) until end of 4 weeks of treatment period (Day 29) plus 7 days of follow-up, up to 36 days.

• Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 15 (C0.083,ss,15)

  At 5 minutes (around 0.083 hours) post dosing at steady state on Day 8 for dose 15 (morning dose on Day 8).

Study Arms (5)

Placebo

PLACEBO COMPARATOR

2 puffs ofmatching placebowere inhaledorally via theRespimat®inhaler twice dailyfor a treatmentperiod of 4 weeksin patients withcystic fibrosis.

Drug: Placebo

BI 1265162 50 μg b.i.d.

EXPERIMENTAL

2 puffs of 25micrograms (μg)BI 1265162(Total: 50μg)were inhaledorally via theRespimat®inhaler twice daily(b.i.d., daily dose:100μg) for atreatment periodof 4 weeks inpatients withcystic fibrosis.

Drug: BI 1265162

BI 1265162 100 μg b.i.d.

EXPERIMENTAL

2 puffs of 50micrograms (μg)BI 1265162(Total: 100μg)were inhaledorally via theRespimat®inhaler twice daily(b.i.d., daily dose:200μg) for atreatment periodof 4 weeks inpatients withcystic fibrosis.

Drug: BI 1265162

BI 1265162 200 μg b.i.d.

EXPERIMENTAL

2 puffs of 100micrograms (μg)BI 1265162(Total: 200μg)were inhaledorally via theRespimat®inhaler twice daily(b.i.d., daily dose:400μg) for atreatment periodof 4 weeks inpatients withcystic fibrosis.

Drug: BI 1265162

BI 1265162 20 μg b.i.d.

EXPERIMENTAL

2 puffs of 10micrograms (μg)BI 1265162(Total: 20μg)were inhaledorally via theRespimat®inhaler twice daily(b.i.d., daily dose:40μg) for atreatment periodof 4 weeks inpatients withcystic fibrosis.

Drug: BI 1265162

Interventions

BI 1265162 DRUG

Inhalation solution

BI 1265162 100 μg b.i.d.; BI 1265162 20 μg b.i.d.; BI 1265162 200 μg b.i.d.; BI 1265162 50 μg b.i.d.

Placebo DRUG

Inhalation solution

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 12 years of age or older at screening;
• Documented diagnosis of cystic fibrosis including:
• positive sweat chloride ≥ 60 mEq/L, by pilocarpine iontophoresis OR
• genotype with 2 identifiable mutations consistent with cystic fibrosis accompanied by one or more clinical features with cystic fibrosis phenotype;
• Patients able to perform acceptable spirometric manoeuvres according to American Thoracic Society (ATS) standards;
• FEV1 ≥ 40% and ≤ 90% of predicted values at screening and predose at Visit 2;
• Women of childbearing potential (WOCBP) must be willing and able to use highly effective methods of birth control per ICH M3 (R2) that result in a failure rate of less than1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient (or patient's legal guardian) information;
• Signed and dated written informed consent and assent in accordance with ICH Harmonized Guideline for Good Clinical Practice (GCP) and local legislation prior to admission in the trial.

You may not qualify if:

• Evidence of acute upper or lower respiratory tract infection within 4 weeks prior to randomization based on investigator's judgement;
• Pulmonary exacerbation requiring use of i.v./oral/inhaled antibiotics or oral corticosteroids within 4 weeks prior to randomisation;
• Patients with history of Acute Tubular Necrosis (ATN);
• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix;
• Patients unable to inhale trial drug in an appropriate manner from the Respimat® inhaler based on investigator's judgement;
• Patients who have started a new chronic medication for CF within 4 weeks of randomisation;
• Patients who have previously received a lung transplant or patients who are currently on a waiting list to receive a lung transplant;
• Patients with a significant history of allergy/hypersensitivity (including medication allergy) which is deemed relevant to the trial as judged by the investigator or with a known hypersensitivity to trial drug or its components. "Significance" in this context refers to any increased risk of hypersensitivity reaction to trial medication;
• Any clinically significant laboratory abnormalities at screening as judged by the investigator, or any of the following:
• Potassium \> upper limit of normal (ULN) in non-haemolysed blood
• Abnormal renal function defined as estimated Glomerular Filtration Rate (eGFR) \< 60ml/min/1.73m²
• Abnormal liver function, defined by serum level of either alanine transaminase (ALT), aspartate transaminase (AST) or total bilirubine ≥ 3 x upper limit of normal (ULN)
• Clinically significant disease or medical condition other than CF or CF-related conditions that, in the opinion of the investigator, would compromise the safety of the patient or the data quality. This includes significant haematological, hepatic, renal, cardiovascular and neurologic disease. Patients with diabetes may participate if their disease is under good control prior to screening;
• Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled;
• Previous randomisation in this trial;

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (26)

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27517, United States

Location

Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Virginia Commonwealth University Health Systems

Richmond, Virginia, 23219, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Brussels - UNIV UZ Brussel

Brussels, 1090, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

St. Paul's Hospital

Vancouver, British Columbia, V1Y 1S1, Canada

Location

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

Location

HOP Arnaud de Villeneuve

Montpellier, 34295, France

Location

HOP Robert Debré

Paris, 75019, France

Location

HOP Cochin

Paris, 75679, France

Location

HOP Lyon Sud

Pierre-Bénite, 69495, France

Location

HOP Perharidy

Roscoff, 29684, France

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, 45239, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH

Giessen, 35385, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Sahlgrenska US, Göteborg

Gothenburg, 413 45, Sweden

Location

Stockholm CF-Center , B59, Huddinge Universitetssjukhus

Stockholm, 141 86, Sweden

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Related Publications (2)

• Goss CH, Fajac I, Jain R, Seibold W, Gupta A, Hsu MC, Sutharsan S, Davies JC, Mall MA. Efficacy and safety of inhaled ENaC inhibitor BI 1265162 in patients with cystic fibrosis: BALANCE-CF 1, a randomised, phase II study. Eur Respir J. 2022 Feb 17;59(2):2100746. doi: 10.1183/13993003.00746-2021. Print 2022 Feb.

  PMID: 34385272 DERIVED

• Goss CH, Jain R, Seibold W, Picard AC, Hsu MC, Gupta A, Fajac I. An innovative phase II trial to establish proof of efficacy and optimal dose of a new inhaled epithelial sodium channel inhibitor BI 1265162 in adults and adolescents with cystic fibrosis: BALANCE-CFTM 1. ERJ Open Res. 2020 Dec 7;6(4):00395-2020. doi: 10.1183/23120541.00395-2020. eCollection 2020 Oct.

  PMID: 33313307 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Limitations and Caveats

This trial was prematurely discontinued with only adult patients being recruited.

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2019
• First Posted: August 16, 2019
• Study Start: September 16, 2019
• Primary Completion: April 16, 2020
• Study Completion: April 24, 2020
• Last Updated: June 4, 2021
• Results First Posted: June 4, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.

Locations

GB (1); US (8); CA (2); DE (5); SE (2); BE (2); FR (5); ES (1)