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

Phase 1

Recruiting

• Conditions: Copd
• Interventions: Drug: TRIXEO AEROSPHERE

• Registration Number: NCT06110403
• Lead Sponsor: University Hospital, Lille

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-21
• Study Start: 2023-09-29
• Status Verified: 2023-10
• Study First Submitted QC: 2023-10-30
• Last Update Submitted: 2023-10-30
• Study First Posted: 2023-10-31
• Last Update Posted: 2023-10-31
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 35

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental group	TRIXEO AEROSPHERE	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Change Plethysmographic Functional residual capacity (FRC)	between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose
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
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
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)
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)
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)
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

Trial Locations

Locations (1)

CHU de Lille; 🇫🇷 Lille, France