COPD - Eosinophil-guided Reduction of Inhaled Corticosteroids (COPERNICOS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gentofte Hospital, Frederiksberg Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

23 Aug 2022 → 16 Dec 2025

Decision date (initial)

2022-08-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-501035-16-01

ClinicalTrials.gov

NCT04481555

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

ICS:
In COPD patients with GOLD class E and/or FEV1 < 30%, an eosinophil-guided administration of ICS treatment regimen is associated with no apparent loss of efficiency.
Azithromycin:
In COPD patients with GOLD class E and/or FEV1 < 30%, the use of low dose Azithromycin can result in a reduction in admissions with COPD exacerbation or death from all causes within 365 days as compared to placebo.

Secondary objectives 5

1. In COPD patients (GOLD risk class C/D and/or FEV1 < 30%) eosinophil-guided administration of inhaled corticosteroid will reduce the use of inhaled corticosteroids by > 25%
2. In COPD patients (GOLD risk class C/D and/or FEV1 < 30%) eosinophil-guided administration of inhaled corticosteroid will reduce the number of ICS related side effects.
3. The respiratory microbiota have a composition of less "pathogenic" bacterial species in COPD patients (GOLD risk class C/D and/or FEV1 < 30%) treated with the eosinophil-guided administration of inhaled corticosteroids regimen than among those treated with continuous triple therapy (ICS/LABA/LAMA) regimen.
4. The complexity of the respiratory microbiota is lower among COPD patients (GOLD risk class C/D and/or FEV1 < 30%) treated with continuous triple therapy (ICS/LABA/LAMA) regimen than among those treated with the eosinophil-guided administration of inhaled corticosteroids regimen.
5. The difference in composition of the respiratory microbiota is substantial when COPD patients (GOLD risk class C/D and/or FEV1 < 30%) are treated with prophylactic low dose Azithromycin

Conditions and MedDRA coding

Chronic obstructive pulmonary disease (COPD)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. COPD (verified by a specialist in respiratory medicine + spirometry).
2. GOLD risk class C/D anytime within the last 2 years (corresponding to 2 ≥ AECOPD and/or ≥1 AECOPD leading to hospitalization during a 12 months period within the last 2 years) and/or FEV1<30%.
3. Must receive at least during last 4 weeks: LAMA, LABA and ICS.
4. Informed consent.

Exclusion criteria 9

1. Known asthma.
2. Male < 40 years.
3. Female <40 years, if non-menopausal (had menstruation within the last 12 months) conditioned by a negative urine HCG test
4. Severe mental illness which considerably complicates co-operation.
5. Language problems that considerably complicate co-operation.
6. Current treatment with systemic corticosteroids corresponding to > 5 mg prednisolone per day.
7. Systemic antibiotic treatment (if to participte in microbiota sub-study) or systemic corticosteroid treatment within 14 days (also prophylactic Azithromycin).
8. Contra-indication to treat with Azithromycin (as listed by the producer).
9. Non-bacterial exacerbation per investigator judgement in the last 3 months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of hospitalization-requiring exacerbations and/or death within 365 days.

Secondary endpoints 16

1. Death or “uncontrolled AECOPD tendency” within 365 days.
2. Number of moderate/severe exacerbation within 365 days.
3. Cumulative dose of inhaled corticosteroids within 365 days.
4. Cumulative dose of systemic corticosteroids within 365 days.
5. Change in lung function (ΔFEV1) from baseline to 365 days.
6. Change in blood eosinophils from baseline to 365 days (eosinophilic trajectories).
7. New diagnosis of diabetes mellitus within 365 days.
8. Change in HbA1c from baseline to 365 days.
9. Antibiotic-requiring infections within 365 days.
10. Difference in respiratory microbiota abundance and diversity at 12 months between treatment arms.
11. Change in COPD-related quality of life (Based on COPD Assessment Test - CAT) from baseline to 365 days.
12. Number who progress to MRC -dyspnea score from < 3 to ≥3 anytime during follow-up (assessed every 3 months).
13. Number of admission requiring NIV treatment or admissions to intensive care within 365 days.
14. Mortality within 365 days.
15. Difference in immunological profile including cytokines and chemokines in the upper airways from baseline to 12 months between treatment arms
16. “Days alive and out of hospital" within 365 days after recruitment

Investigational products

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

Test 4

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gentofte Hospital

Sponsor organisation

Gentofte Hospital

Address

Kildegaardsvej 28

City

Hellerup

Postcode

2900

Country

Denmark

Scientific contact point

Organisation

Gentofte Hospital

Contact name

Pradeesh Sivapalan

Public contact point

Organisation

Gentofte Hospital

Contact name

Pradeesh Sivapalan

Third parties 1

Frederiksberg Hospital

Sponsor organisation

Frederiksberg Hospital

Address

Nordre Fasanvej 57, 1st Floor Entrance 2 1st Floor Entrance 2

City

Frederiksberg

Postcode

2000

Country

Denmark

Sponsor responsibilities

Article 77 compliance

Gentofte Hospital

Contact point sponsor

Gentofte Hospital

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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