Molecular signatures associated with response to ICS treatment in patients with COPD stratified by eosinophil levels

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio De Recerca Clinic Barcelona-Institut D’investigacions Biomediques August Pi I Sunyer

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

12 Feb 2025 → ongoing

Decision date (initial)

2024-07-18

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

IMI 13. Funding. EU Grant Agreement Number: 831434 — 3TR — H2020-JTI-IMI2-2018-14-two-stage

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To determine the molecular changes associated with the use of ICS in COPD patients with different blood eosinophil counts.

Secondary objectives 5

1. To determine the molecular changes associated with the use of ICS in COPD patients with different airflow limitation severity (FEV1 % ref.).
2. To compare the identified molecular changes with available data obtained during an exacerbation event in previous studies. This will be done by calculating the percentage of enrichment and/or overlap with molecular data obtained in this study, with that from previous studies on exacerbation episodes.
3. To compare the identified molecular changes with available data from stable COPD patients of previous longitudinal studies. This will be done by calculating the percentage of enrichment and/or overlap of the obtained data, with the data from previous studies, which have information on outcomes of interest such as subsequent number of exacerbations and lung function decline.
4. To compare the data obtained in the 3TR-ICS COPD with the other 3TR consortium diseases (e.g. transcriptome and/or proteins and/or epigenome, etc.).
5. To determine changes in FEV1 associated with the use of ICS in COPD patients.

Conditions and MedDRA coding

Chronic obstructive pulmonary disease (COPD)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male and female patients ≥40 years of age.
2. ≥ 10 pack-years smoking.
3. Former smokers (≥6 months).
4. post-bronchodilator FEV1/FVC<0.70.
5. FEV1 ≥30 (i.e. mild-moderated COPD patients).
6. Signed written informed consent form.
7. On regular treatment with dual long-acting bronchodilators (LABA+LAMA), minimum 8 weeks of usage.
8. Women of child-bearing potential must have a negative pregnancy test in serum or urine before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence.
9. Hormonal contraceptive methods will be avoided due to the risk of adverse events and impairment of liver function.

Exclusion criteria 14

1. Presence of other respiratory disorders, (i.e. current physician diagnosis of asthma, early life history of asthma (<21 years) a previous clinical diagnosis of bronchiectasis, interstitial lung disease, pulmonary eosinophilia).
2. Primary or secondary immunodeficiency.
3. Immunosuppression or regular oral corticosteroid treatment.
4. Allergy to IMP’s excipients.
5. Any circumstances which could contradict study participation and lead the investigator to assess the patient as unsuitable for study participation for any other reason.
6. Long-term oxygen therapy or non-invasive mechanical ventilation at home.
7. Current smokers.
8. Active cancer.
9. Use of ICS in the 3 months prior to the recruitment.
10. Participating in another randomized trial.
11. Not likely to complete the study.
12. Pregnant or breastfeeding females.
13. Exacerbations in the previous 8 weeks.
14. Blood eosinophil count <100 eos/mcL

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Significant molecular changes (p<0.05, and/or FDR<0.05) (e.g. microbiome and/or transcriptome and/or proteins and/or epigenetics) in sputum, nasal and oropharyngeal swabs, urine and/or blood associated with ICS treatment vs. no ICS treatment (usual care), in COPD stratified by their blood eosinophil counts. The changes will be calculated as variations from Visit 2 to Visit 3 (8 weeks).

Secondary endpoints 1

1. Significant molecular changes (p<0.05, and/or FDR<0.05) (e.g. microbiome and/or transcriptome and/or proteins and/or epigenetics) in sputum, nasal and oropharyngeal swabs, urine and/or blood associated with ICS treatment vs. no ICS treatment (usual care), in COPD with different airflow limitation severities. The molecular changes will be calculated as variations from Visit 2 to Visit 3.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio De Recerca Clinic Barcelona-Institut D’investigacions Biomediques August Pi I Sunyer

Sponsor organisation

Fundacio De Recerca Clinic Barcelona-Institut D’investigacions Biomediques August Pi I Sunyer

Address

Calle Rosellon 149-153

City

Barcelona

Postcode

08036

Country

Spain

Scientific contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’investigacions Biomediques August Pi I Sunyer

Contact name

Rosa Faner

Public contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’investigacions Biomediques August Pi I Sunyer

Contact name

Rosa Faner

Locations

3 EU/EEA countries · 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 13 files

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

Application history

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