The efficacy and safety of two doses of CHF6001 DPI as add-on to maintenance COPD triple therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Chiesi Farmaceutici S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

17 Jun 2021 → 23 Dec 2025

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Chiesi Farmaceutici S.p.A.

External identifiers

EU CT number

2023-510174-13-00

EudraCT number

2020-003648-97

ClinicalTrials.gov

NCT04636814

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacoeconomic, Dose response

To evaluate the efficacy of two doses of CHF6001 add-on to maintenance triple therapy (free or fixed combination of ICS, LABA, LAMA) to reduce the rate of moderate and severe exacerbations after 52 weeks of treatment in comparison with maintenance triple therapy (i.e. placebo arm).

Secondary objectives 4

1. To evaluate the efficacy of the two doses of CHF6001 add-on to maintenance triple therapy on health-related quality of life after 52 weeks of treatment (change in SGRQ total score).
2. To evaluate the efficacy of the two doses of CHF6001 add-on to maintenance triple therapy on lung function, health-related quality of life, severe exacerbations in the pooled analysis of CLI-06001AA1-04 Main cohort (excluding subjects enrolled in China) and CLI-06001AA1-05 studies and other clinical outcome measures in comparison with maintenance triple therapy.
3. To evaluate the safety and tolerability of the two doses of CHF6001.
4. To evaluate the efficacy, safety and tolerability of the two doses of CHF6001 in comparison with Roflumilast.

Conditions and MedDRA coding

Chronic Obstructive Pulmonary Disease (COPD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Males and females aged ≥ 40 years with written informed consent obtained prior to any study related procedure.
2. Females are eligible to enter the study if they are of a. non- childbearing potential, b. childbearing potential, they must have a negative pregnancy test at screening and must agree to use one or more of the acceptable contraceptive measures.
3. Subjects with an established diagnosis of COPD with chronic bronchitis.
4. Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years.
5. A post-bronchodilator FEV1 < 50% of the patient predicted normal value and a postbronchodilator FEV1/FVC ratio < 0.7 after 400μg (4 puffs x 100μg) of salbutamol pMDI or equivalent dose of albuterol pMDI in the US.
6. A documented history (e.g. medical record verification) of at least one moderate or severe COPD exacerbation in the previous year.
7. Symptomatic subject at screening defined as having a CAT score ≥10.
8. Subjects prescribed with maintenance triple therapy (free or fixed combination of ICS, LABA, LAMA) according to GOLD 2020 recommendations, for at least 12 months prior to screening and receiving regular maintenance triple therapy for at least 3 months prior to the screening visit. ICS must be in an approved dose for COPD.
9. Subjects are willing and able to be trained to use correctly the DPI inhalers (NEXThaler®).
10. Subjects are willing and able to be trained to use correctly the electronic devices with COPD questionnaires, to understand and to perform required outcome measurements of the protocol (e.g.spirometry maneuvers etc.) and ability to understand the risks involved.

Exclusion criteria 16

1. Subjects with a diagnosis of current asthma.
2. Subjects with a moderate or severe COPD exacerbation 4 weeks prior to study entry and during run-in period.
3. Pregnant and lactating women.
4. Subjects requiring long term (at least 15 hours daily) oxygen therapy for chronic hypoxemia.
5. Subjects with known α-1 antitrypsin deficiency as the underlying cause of COPD.
6. Subjects with primary diagnosis of emphysema not related to COPD.
7. Subjects with clinically significant respiratory disorders other than COPD.
8. Subjects with lung volume reduction surgery.
9. Subjects having lung cancer or a history of lung cancer with full recovery less than 1 year after completing cancer therapy.
10. Subjects with active cancer or a history of cancer (other than the lung) with full recovery less than 1 year after completing cancer therapy or any untreated localized carcinoma.
11. Subjects with a history of allergy or hypersensitivity to anticholinergics, β2-agonists,corticosteroids, PDE-4 inhibitors or any of the excipients contained in any of the formulations used in the trial or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the investigator's opinion would contra-indicate study participation.
12. Subjects under Roflumilast treatment within 6 months before study entry.
13. Subjects with a diagnosis of depression, generalized anxiety disorder, suicidal ideation or behavior that might, according to the investigator judgement, place the patient at undue risk.
14. Subjects who have clinically significant cardiovascular condition.
15. An abnormal and clinically significant 12-lead ECG finding in relation to the subject's medical history that results in active medical problem which may impact the safety of the patient according to investigator's judgement.
16. Subjects with a significant neurological disease including transient ischemic attack (TIA), stroke, seizure disorder or behavioural disturbances that in investigator's opinion, would place the patient at risk by participating to the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annual rate of moderate and severe exacerbations over 52 weeks.

Secondary endpoints 5

1. •Change from baseline in SGRQ Total score at week 52 •Time to first moderate/severe exacerbation •Annual rate of severe exacerbations •Time to first severe exacerbation
2. •Change from baseline in morning pre-dose of FEV1 at week 52 •Change from baseline in SGRQ Domain scores at week 52
3. •SGRQ response (i.e., change from baseline in SGRQ score ≤-4) at week 52 •Change from baseline to last inter-visit period (week 40-52) in the average E-RS total and sub-scale scores
4. •E-RS response (i.e., change from baseline in E-RS total score ≤ -2) at week 52 •Change from baseline to last inter-visit period (week 40-52) in the percentage of days without intake of rescue medication and in the average daily use of rescue medication (number of puffs/day)
5. •Time to study medication discontinuation due to any reason •Time to first moderate or severe exacerbation or study medication discontinuation due to class related adverse events, lack of efficacy or death, (composite endpoint) and time to its individual components

Investigational products

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

Test 2

Comparator 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Chiesi Farmaceutici S.p.A.

Sponsor organisation

Chiesi Farmaceutici S.p.A.

Address

Via Palermo 26 A

City

Parma

Postcode

43122

Country

Italy

Scientific contact point

Organisation

Chiesi Farmaceutici S.p.A.

Contact name

GLOBAL CLINICAL DEVELOPMENT

Public contact point

Organisation

Chiesi Farmaceutici S.p.A.

Contact name

GLOBAL CLINICAL DEVELOPMENT

Third parties 8

Locations

14 EU/EEA countries · 141 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 100 files

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

Application history

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