VARI-OSCIL: Impact of Long-acting Bronchodilator- -Corticoid Inhaled Therapy on Ventilation, Lung Function and Breathlessness

Sponsor

University Hospital, Lille (Other)

Overall Status

Recruiting

CT.gov ID

NCT06110403

Collaborator

AstraZeneca (Industry)

Enrollment

Location

Arm

23.1

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Copd	Drug: TRIXEO AEROSPHERE	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Impact of Inhaled BGF 160 on Complexity and Variability of Tidal Breathing and Oscillatory Mechanics in Stable COPD Patient

Actual Study Start Date :

Sep 29, 2023

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental group Symptomatic COPD patients in stable condition treated with BGF 160 (Trixéo Aerosphere®), a combination of budesonide, formoterol and glycopyrronium in a metered dose inhaler, taken twice a day	Drug: TRIXEO AEROSPHERE BGF 160 (Breztri Aerosphere™ in USA, Trixeo™ in France) Inhalation aerosol: pressurized metered dose inhaler containing a combination of budesonide (160 mcg), glycopyrrolate (9 mcg) and formoterol fumarate (4.8 mcg) as an inhalation aerosol. Oral inhalation: 2 inhalations of BGF 160 twice daily for 30 days.

Arm

Intervention/Treatment

Experimental: Experimental group

Symptomatic COPD patients in stable condition treated with BGF 160 (Trixéo Aerosphere®), a combination of budesonide, formoterol and glycopyrronium in a metered dose inhaler, taken twice a day

Drug: TRIXEO AEROSPHERE

BGF 160 (Breztri Aerosphere™ in USA, Trixeo™ in France) Inhalation aerosol: pressurized metered dose inhaler containing a combination of budesonide (160 mcg), glycopyrrolate (9 mcg) and formoterol fumarate (4.8 mcg) as an inhalation aerosol. Oral inhalation: 2 inhalations of BGF 160 twice daily for 30 days.

Outcome Measures

Primary Outcome Measures

change in ventilation pattern complexity and variability [between V2 baseline (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose at one month)]
Noise limit: % Lyapounov component: bits/iteration no combination possible

Secondary Outcome Measures

Change impulse oscillometry or forced oscillation: resistances at 5Hz, reactance at 5Hz [between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose]
resistance and reactance: kPa/L/s
Changes in FEV1 (spirometry) [between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose]
Change Plethysmographic Functional residual capacity (FRC) [between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose]
Changes measurement for noise limit, respiratory frequency, volume, largest Lyapounov component, resistances at 5Hz, reactance at 5Hz, FEV1and FRC versus TDI at V3 [between V2 base measurement (pre-treatment) and V3 peak (2 hours (+/-30min)]
TDI at V3 (in term of continuous variable and in term of binary variable "responder/non responder"; a response is defined by a change in TDI ≥ +1 between baseline and V3)
Baseline dyspnea index ( BDI) [before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month)]
Transition dyspnea index (TDI) [before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month)]
Modified dyspnea profile ( MDP) [before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month)]
CAT score : COPD assessment test, [before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes at one month)]
range 0 to 40, 40 meaning the worst condition
Likert scale for dyspnea and general health [before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month)]
Likert scale change in dyspnea : - 3 to + 3, + 3 maximal improvement, -3 maximal deterioration Likert scale change in general health : - 3 to + 3, + 3 maximal improvement, -3 maximal deterioration

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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