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Cystic FibrosisPhase 2NCT04059094

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

A Phase 2 study testing BI 1265162 in people with Cystic Fibrosis, run by Boehringer Ingelheim at 26 sites in 8 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Cystic Fibrosis
What is being tested?
BI 1265162
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
52 participants
Where
26 sitesin 8 countries
Study dates
16 Sep 2019to 24 Apr 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

26 sites in 8 countries.

26 sites in 8 countries

United States8 sites

  • The University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27517

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Riley Hospital for Children at Indiana University Health

    Indianapolis, Indiana, 46202

  • Nemours Children's Hospital

    Orlando, Florida, 32827

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

    Pittsburgh, Pennsylvania, 15224

  • Virginia Commonwealth University Health Systems

    Richmond, Virginia, 23219

  • University of Washington

    Seattle, Washington, 98195

Other trials in United States

France5 sites

  • HOP Arnaud de Villeneuve

    Montpellier, 34295

  • HOP Robert Debré

    Paris, 75019

  • HOP Cochin

    Paris, 75679

  • HOP Lyon Sud

    Pierre-Bénite, 69495

  • HOP Perharidy

    Roscoff, 29684

Other trials in France

Germany5 sites

  • Charité - Universitätsmedizin Berlin

    Berlin, 13353

  • Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

    Essen, 45239

  • Universitätsklinikum Gießen und Marburg GmbH

    Giessen, 35385

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Universitätsklinikum Tübingen

    Tübingen, 72076

Other trials in Germany

Belgium2 sites

  • Brussels - UNIV UZ Brussel

    Brussels, 1090

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

Canada2 sites

  • Centre Hospitalier de l'Universite de Montreal (CHUM)

    Montreal, Quebec, H2X 3E4

  • St. Paul's Hospital

    Vancouver, British Columbia, V1Y 1S1

Other trials in Canada

Sweden2 sites

  • Sahlgrenska US, Göteborg

    Gothenburg, 413 45

  • Stockholm CF-Center , B59, Huddinge Universitetssjukhus

    Stockholm, 141 86

Other trials in Sweden

Spain1 site

  • Hospital Vall d'Hebron

    Barcelona, 08035

Other trials in Spain

United Kingdom1 site

  • Royal Brompton Hospital

    London, SW3 6NP

Other trials in United Kingdom

About this study

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

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
Being tested
BI 1265162, Placebo
Medical subject headings
Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BI 1265162Drug

    Inhalation solution

  • PlaceboDrug

    Inhalation solution

Study groups in NCT04059094
Study groupRoleWhat they receive
PlaceboPlacebo comparator2 puffs ofmatching placebowere inhaledorally via theRespimat®inhaler twice dailyfor a treatmentperiod of 4 weeksin patients withcystic fibrosis.
Receives: Drug: Placebo
BI 1265162 50 μg b.i.d.Experimental2 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.
Receives: Drug: BI 1265162
BI 1265162 100 μg b.i.d.Experimental2 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.
Receives: Drug: BI 1265162
BI 1265162 200 μg b.i.d.Experimental2 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.
Receives: Drug: BI 1265162
BI 1265162 20 μg b.i.d.Experimental2 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.
Receives: Drug: BI 1265162

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)

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

    Change from baseline in Lung Clearance Index (LCI) assessed by N2 Multiple Breath Washout (N2MBW) procedure after 4 weeks of treatment was reported. LCI was calculated as the ratio of cumulative expired volume (CEV) to functional residual capacity (FRC), which was LCI = CEV (milliliter/kilogram) / FRC (milliliter/kilogram) and hence, LCI was "Unitless". The change from baseline after 4 weeks of treatment in LCI was then calculated as the LCI value measured after 4 weeks of treatment at Day 29 minus the LCI value measured at baseline on Day 1.

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

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

    The adult/adolescent format of the CFQ-R consists of 50 questions (qts) dividing into 12 domains: Physical functioning(8 qts), role limitations(4 qts), vitality(4 qts), emotional functioning(5 qts), social functioning(6 qts), body image(3 qts), eating disturbance(3 qts), treatment burden(3 qts), health perceptions(3 qts), weight(1 qts), respiratory symptoms(7 qts), and digestive system(3 qts). The score of some qts is first reversed if reversed coded, so that the score for each of the 50 qts ranges from 1 to 4 points (less symptoms). Then, a domain score for a domain with N qts is calculated as (sum of the scores of the N qts - N)/(N ✕ 4 - N) ✕ 100. Each domain score ranges from 0 to 100 (better health). The CFQ-R total score is summing up the domain scores and ranges from 0 to 1200 (better quality of life). The change from baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) total score after 4 weeks of treatment was reported.

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

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

    The 20-item Sputum Assessment Questionnaire (CASA-Q) consisted of 4 domains: Cough Symptoms Domain (3 items), Cough Impact Domain (8 items), Sputum Symptoms Domain (3 items), and Sputum Impact Domain (6 items). Score of each item has been reversed such that better responses have higher score, which ranges from 1 (worse) to 5 (better health). For each domain, the domain score was calculated by summing up the scores of the respective items and scaling to a value ranging from 0 to 100, with higher score associated with fewer symptoms/less impact due to cough or sputum. The 4 domain scores (sub-scores) were reported.

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

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

    Percentage of patients with any treatment-emergent Adverse Events (AE) up to day 36 was reported.

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

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

    Concentration of BI 1265162 in plasma at 0.083 hour at steady state following dose 15 (C0.083,ss,15) was reported.

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

  6. Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 57 (C0.083,ss,57)

    Concentration of BI 1265162 in plasma at 0.083 hour at steady state following dose 57 (C0.083,ss,57) was reported.

    Measured: At 5 minutes (around 0.083 hours) post dosing at steady state on Day 29 for dose 57 (morning dose on Day 29).

  7. Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 15 (Cpre,ss, 15)

    Pre-dose concentration measured of BI 1265162 in plasma at steady state after dose 15 (Cpre,ss, 15) was reported.

    Measured: At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 8 for dose 15 (morning dose on Day 8).

  8. Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 57 (Cpre,ss, 57)

    Pre-dose concentration measured of BI 1265162 in plasma at steady state after dose 57 (Cpre,ss, 57) was reported.

    Measured: At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 29 for dose 57 (morning dose on Day 29).

  9. 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)

    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) was reported.

    Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2019
  2. Study start16 Sep 2019
  3. Primary completion16 Apr 2020
  4. Study completion24 Apr 2020

Why it stopped: Not due to safety reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04059094
Sponsor's protocol ID
1399-0003
Other IDs
2019-000261-21, 2019
Status last verified
May 2021
First submitted
15 Aug 2019
Last updated
4 Jun 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https:// trials.boehringer-ingelheim.com/trial\_results/ clinical\_submission\_documents.html to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link http://trials.boehringeringelheim. com/ to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.

Publications

  • 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.

    PubMed 34385272

  • 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.

    PubMed 33313307

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BI 1265162 in people with Cystic Fibrosis, run by Boehringer Ingelheim at 26 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, France, Germany, Belgium, Canada and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment (time frame: At 30 minutes prior to dosing in Day 1 (baseline) and Day 29 (end of 4-week treatment period).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04059094, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2021.

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Clinical Trial NCT04059094 | AzTrials