Clinical trial NCT06110403: Impact of Long-acting Bronchodilator- -Corticoid Inhaled Therapy on Ventilation, Lung Function and Breathlessness
Official title: Impact of Inhaled BGF 160 on Complexity and Variability of Tidal Breathing and Oscillatory Mechanics in Stable COPD Patient
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Copd
Keywords: COPD
bronchodilator
ventilatory mode
variability
forced oscillations
spirometry
plethysmography
dyspnea
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2023-10-31
Enrollment: 35
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Multicentre, prospective, non-randomised, single-arm, open label, mechanistic study to investigate the mechanism of action of BGF 160 on ventilation pattern complexity and variability


Eligibility criteria: Inclusion Criteria:

* Provision of signed informed consent prior to any study specific procedure
* Female or male subjects aged 40-75 years inclusive at the time of enrolment (Visit 1)
* Documented history of COPD with a post-bronchodilator FEV1/FVC \<0.70 and a post-bronchodilator 30 % \< FEV1 \<70% of predicted normal value (according to ERS 1993 reference values for spirometry ) at screening
* Smoking history \> 10 pack-years
* Baseline significant dyspnea with a mMRC ≥ 2

Exclusion Criteria:

* History or current diagnosis of asthma or ACOS (asthma-COPD overlap syndrome)
* Respiratory infection or COPD exacerbation within 6 weeks (2 months if it resulted in hospitalization) prior to screening
* Clinically significant or relevant cardiovascular conditions, laboratory tests, electrocardiogram (ECG) parameters:

  * Unstable angina/acute coronary syndrome, or Coronary Artery Bypass Grafting (CABG), Percutaneous Coronary Intervention (PCI) or myocardial infarction within the past 6 months.
  * Congestive heart failure New York Heart Association (NYHA) class III/IV.
  * Structural heart disease (hypertrophic cardiomyopathy, significant valvular disease).
  * Paroxysmal (within the past 6 months) or symptomatic chronic cardiac tachyarrhythmia.
  * Left bundle branch or high-degree AV block (second degree AV block type 2 and third degree AV block) unless the patient has a pacemaker.
  * Sinus node dysfunction with pauses.
  * Ventricular pre-excitation and/or Wolff-Parkinson-White syndrome.
  * QTcF interval \>470 msec (QT interval corrected using Fridericia's formula; QTcF=QT/\[RR1/3\]).
  * Any other ECG abnormality deemed clinically significant by the Investigator.
  * Bradycardia with ventricular rate \< 45 bpm.
  * Uncontrolled hypertension (\> 165/95 mmHg).
* Clinically relevant respiratory conditions (other than COPD)
* Severe renal impairment eGFR \< 30
* Hepatic impairment
* Narrow-angle glaucoma that, in the opinion of the Investigator, has not been adequately treated.
* Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that is clinically significant
* Patients not able to perform IOS, spirometry, plethysmography, or VT acquisition (10 min)
* Any contraindication to LABA or LAMA drugs or to Inhaled corticosteroids
* Pregnancy or breastfeeding
* Woman of childbearing age without effective contraception
* Any type of cancer within 5 years
* Patients under guardianship
* Refuse or incapacity to give an informed consent
* Absence of social insurance

Primary outcomes:
measure: change in ventilation pattern complexity and variability
timeFrame: between V2 baseline (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose at one month)
Secondary outcomes:
measure: Change impulse oscillometry or forced oscillation: resistances at 5Hz, reactance at 5Hz
timeFrame: between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose
measure: Changes in FEV1 (spirometry)
timeFrame: between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose
measure: Change Plethysmographic Functional residual capacity (FRC)
timeFrame: between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose
measure: Changes measurement for noise limit, respiratory frequency, volume, largest Lyapounov component, resistances at 5Hz, reactance at 5Hz, FEV1and FRC versus TDI at V3
timeFrame: between V2 base measurement (pre-treatment) and V3 peak (2 hours (+/-30min)
measure: Baseline dyspnea index ( BDI)
timeFrame: before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month)
measure: Transition dyspnea index (TDI)
timeFrame: before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month)
measure: Modified dyspnea profile ( MDP)
timeFrame: before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month)
measure: CAT score : COPD assessment test,
timeFrame: before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes at one month)
measure: Likert scale for dyspnea and general health
timeFrame: before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month)
Other outcomes:
Locations:
city: Lille
country: France
facility: CHU de Lille
Study officials:
affiliation: University Hospital, Lille
name: Thierry PEREZ, MD
role: PRINCIPAL_INVESTIGATOR
References: