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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Lille

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

16 Dec 2024 → ongoing

Decision date (initial)

2024-12-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Astra Zeneca

External identifiers

EU CT number

2024-514097-52-00

EudraCT number

2022-003784-15

ClinicalTrials.gov

NCT06110403

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy

To evaluate the change in ventilation pattern complexity and variability after 1 month of treatment by BGF 160

Secondary objectives 4

1. To assess the change in Oscillatory mechanics, Flows and Lung volumes one month after administration of BGF 160
2. To assess the association between clinical response on dyspnea (TDI at V3) and the changes of variability/PFT between V2 and V3
3. To compare dyspnea and symptoms before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30min) at one month)
4. To compare the ventilation pattern variability and complexity at the other time points : - V2 baseline vs V2 peak (first dose effect) - V2 baseline vsV3 trough (residual effect)

Conditions and MedDRA coding

Impact of inhaled BGF 160 on complexity and variability of tidal breathing and oscillatory mechanics in stable COPD patient

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Provision of signed informed consent prior to any study specific procedure
2. Female or male subjects aged 40-75 years inclusive at the time of enrolment (Visit 1)
3. 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
4. Smoking history > 10 pack-years
5. Baseline significant dyspnea with a mMRC ≥ 2

Exclusion criteria 18

1. History or current diagnosis of asthma or ACOS (asthma-COPD overlap syndrome)
2. Respiratory infection or COPD exacerbation within 6 weeks (2 months if it resulted in hospitalization) prior to screening
3. Clinically significant or relevant cardiovascular conditions, laboratory tests, electrocardiogram (ECG) parameters: o Unstable angina/acute coronary syndrome, or Coronary Artery Bypass Grafting (CABG), Percutaneous Coronary Intervention (PCI) or myocardial infarction within the past 6 months. o Congestive heart failure New York Heart Association (NYHA) class III/IV. o Structural heart disease (hypertrophic cardiomyopathy, significant valvular disease). o Paroxysmal (within the past 6 months) or symptomatic chronic cardiac tachyarrhythmia. o 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. o Sinus node dysfunction with pauses. o Ventricular pre-excitation and/or Wolff-Parkinson-White syndrome. o QTcF interval >470 msec (QT interval corrected using Fridericia's formula; QTcF=QT/[RR1/3]). o Any other ECG abnormality deemed clinically significant by the Investigator. o Bradycardia with ventricular rate < 45 bpm. o Uncontrolled hypertension (> 165/95 mmHg).
4. Clinically relevant respiratory conditions (other than COPD)
5. Severe renal impairment eGFR < 30
6. Hepatic impairment
7. Narrow-angle glaucoma that, in the opinion of the Investigator, has not been adequately treated.
8. Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that is clinically significant
9. Patients not able to perform IOS, spirometry, plethysmography, or VT acquisition (10 min)
10. Any contraindication or allergy to LABA or LAMA drugs or to Inhaled corticosteroids
11. Treatment by an azole systemic antifungal (itraconazole, fluconazole…)
12. Treatment by a protease inhibitor or cobicistat for HIV
13. Pregnancy or breastfeeding
14. Woman of childbearing age without effective contraception
15. Any type of cancer within 5 years
16. Patients under guardianship
17. Refuse or incapacity to give an informed consent
18. Absence of social insurance

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Multiple primary endpoints characterizing the change in ventilation pattern complexity and variability between V2 baseline (pre-treatment) and V3 peak (2 hours (+/-30min) post dose at one month) : noise limit, respiratory frequency, volume and largest Lyapounov component (an indicator of the sensitivity of the system to initial condition.

Secondary endpoints 4

1. Change between V2 base (pre-treatment) and V3 peak (2 hours (+/-30min) post dose) of : - Impulse oscillometry or forced oscillation: resistances at 5Hz, reactance at 5Hz - Spirometry: Changes in FEV1 - Plethysmographic Functional residual capacity (FRC)
2. Changes between V2 base measurement (pre-treatment) and V3 peak (2 hours (+/-30min) measurement for noise limit, respiratory frequency, volume, largest Lyapounov component, resistances at 5Hz, reactance at 5Hz, FEV1and FRC versus 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)
3. Dyspnea and symptom scores: - Baseline dyspnea index ( BDI) - Transition dyspnea index (TDI) - Modified dyspnea profile ( MDP) - CAT score - Likert scale for dyspnea and general health
4. Noise limit, respiratory frequency, volume, largest Lyapounov component, resistances at 5Hz, reactance at 5Hz, FEV1, FRC, and VAS dyspnea/chest tightness

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Lille

Sponsor organisation

Centre Hospitalier Universitaire De Lille

Address

2 Avenue Oscar Lambret, Cs 70001 Cs 70001

City

Lille Cedex

Postcode

59037

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Lille

Contact name

Thierry PEREZ

Public contact point

Organisation

Centre Hospitalier Universitaire De Lille

Contact name

Thierry PEREZ

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications