Clinical trial NCT04059094: 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
Official title: A Randomised, Double-blind, Placebo-controlled and Parallel Group Trial to Evaluate Efficacy and Safety of Twice Daily Inhaled Doses of BI 1265162 Delivered by Respimat® Inhaler as add-on Therapy to Standard of Care Over 4 Weeks in Patients With Cystic Fibrosis - BALANCE - CF™ 1
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-08-16
Enrollment: 52
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;
* Currently enrolled in another investigational device or drug trial, or less than 30 days or six half-lives (whichever is greater) since ending another investigational device or drug trial(s), or receiving other investigational treatment(s);
* Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial;
* Women who are pregnant, nursing, or who plan to become pregnant while in the trial.

Primary outcomes:
measure: Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment
timeFrame: At 30 minutes prior to dosing in Day 1 (baseline) and Day 29 (end of 4-week treatment period).
Secondary outcomes:
measure: Change From Baseline in Lung Clearance Index (LCI) Assessed by N2 Multiple Breath Washout (N2MBW) Procedure After 4 Weeks of Treatment
timeFrame: At pre-dose in Day 1 (baseline) and Day 29 (end of 4-week treatment period).
measure: Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment
timeFrame: At Day 1 (baseline) and Day 29 (end of 4-week treatment period).
measure: Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment
timeFrame: At Day 1 (baseline) and Day 29 (end of 4-week treatment period).
measure: Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36
timeFrame: From Day 1 (baseline) until end of 4 weeks of treatment period (Day 29) plus 7 days of follow-up, up to 36 days.
measure: Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 15 (C0.083,ss,15)
timeFrame: At 5 minutes (around 0.083 hours) post dosing at steady state on Day 8 for dose 15 (morning dose on Day 8).
measure: Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 57 (C0.083,ss,57)
timeFrame: At 5 minutes (around 0.083 hours) post dosing at steady state on Day 29 for dose 57 (morning dose on Day 29).
measure: Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 15 (Cpre,ss, 15)
timeFrame: At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 8 for dose 15 (morning dose on Day 8).
measure: Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 57 (Cpre,ss, 57)
timeFrame: At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 29 for dose 57 (morning dose on Day 29).
measure: Area Under the Concentration-time Curve of BI 1265162 in Plasma From 0 to 4 Hours at Steady State After Dose 15 (AUC0-4,ss,15)
timeFrame: At pre-dose (taken within 60 minutes prior to dosing) and 5 minutes (min), 30 min, 1 hour, and 4 hours post dosing at steady state on Day 8 for dose 15 (morning dose on Day 8).
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Health Systems
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Brussels
country: Belgium
facility: Brussels - UNIV UZ Brussel
city: Leuven
country: Belgium
facility: UZ Leuven
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Montpellier
country: France
facility: HOP Arnaud de Villeneuve
city: Paris
country: France
facility: HOP Robert Debré
city: Paris
country: France
facility: HOP Cochin
city: Pierre-Bénite
country: France
facility: HOP Lyon Sud
city: Roscoff
country: France
facility: HOP Perharidy
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Essen
country: Germany
facility: Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Göteborg
country: Sweden
facility: Sahlgrenska US, Göteborg
city: Stockholm
country: Sweden
facility: Stockholm CF-Center , B59, Huddinge Universitetssjukhus
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
References:
citation: 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.
citation: 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.