A study comparing Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination CHF5993 With the Fixed Dose Dual Combination CHF1535 in Subjects With COPD (TRITON)

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

22 Apr 2022 → 13 Jan 2026

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

commercial

External identifiers

EU CT number

2023-510172-31-00

EudraCT number

2020-002389-16

ClinicalTrials.gov

NCT04320342

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy, Pharmacokinetic

To demonstrate the efficacy of CHF 5993 to improve pre-dose lung function (pre-dose morning forced expiratory volume in 1 second [FEV1]) compared with CHF 1535 in subjects with COPD.

Secondary objectives 5

1. To demonstrate the efficacy of CHF 5993 to improve post-dose lung function (2-hour post dose FEV1) compared with CHF 1535 in subjects with COPD.
2. To demonstrate the efficacy of CHF 5993 to reduce the annual rate of moderate and severe COPD exacerbations compared with CHF 1535 in subjects with COPD.
3. To demonstrate the efficacy of CHF 5993 to improve health-related quality of life (decrease from baseline in total SGRQ score ≥4) compared with CHF 1535 in subjects with COPD.
4. To assess the long-term safety and tolerability of CHF 5993 compared with CHF 1535 in subjects with COPD.
5. To evaluate the effect of CHF 5993 on other lung function parameters, subject's health status and clinical outcome measures compared with CHF 1535 in subjects with COPD.

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 12

1. signed and dated written informed consent must be obtained prior to initiating any study related procedures
2. Outpatient population
3. Male or female subjects aged ≥ 40 years
4. For Woman of Childbearing Potential with fertile / non-fertile male partners and for Female subjects of nonchildbearing potential
5. COPD diagnosis for at least 12 months before the screening visit (V1) in accordance with the definition by the GOLD 2020 Report
6. Current or ex-smokers who quit smoking at least 6 months prior to screening with a smoking history of at least 10 pack-years
7. Symptomatic subjects based on COPD Assessment Test (CAT) score ≥ 10
8. A pre- and post-bronchodilator FEV1/FVC ratio <0.70 at screening
9. A post-bronchodilator FEV1 <50% predicted normal at screening and a documented history of ≥1 moderate or severe COPD exacerbation in the previous 12 months OR a post-bronchodilator FEV1 ≥50% and <80% of predicted normal at screening and a documented history of ≥2 moderate COPD exacerbations or ≥1 severe COPD exacerbation in the previous 12 months Global Lung Function Initiative reference equations will be used to calculate percent predicted values (for COPD exacerbation details see study protocol).
10. Subjects receiving daily inhaled maintenance therapy for their COPD, at a stable dose for at least 3 months prior to the screening and randomization visits
11. Documentation (including imagery and report) of chest x-ray (CXR) or CT scan performed within 6 months prior to the screening visit, without evidence of significant abnormalities (other than those related to the presence of COPD).
12. A cooperative attitude and ability to demonstrate correct use of the pMDI inhalers and eDiary

Exclusion criteria 14

1. Female subjects who are pregnant (as evident by a positive urine hCG or serum β-hCG test) or lactating
2. Subjects using the following medications prior to the screening visit and during the run-in period: a. Systemic/oral/parenteral corticosteroids in the prior 4 weeks b. Antibiotics for a lower respiratory tract infection (e.g. pneumonia) or COPD exacerbation in the prior 4 weeks c. Any long-term chronic maintenance use of antibiotic treatment in the prior 4 weeks d. Oral xanthine derivatives (e.g. theophylline) in the prior 7 days
3. A moderate or severe COPD exacerbation or a lower respiratory tract infection (e.g., pneumonia) that has not resolved ≤14 days prior to the screening visit or during the run-in period
4. Subjects being treated with non-cardioselective β-blockers
5. Subjects requiring long term (> 15 hours daily) oxygen therapy
6. Known respiratory disorders other than COPD which may impact the efficacy of the study drug according to investigator's judgement.
7. Lung transplant surgery or lung volume reduction surgery
8. Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator, would prevent use of anticholinergic agents
9. History of hypersensitivity to M3 receptor antagonists, β2 agonists, corticosteroids or any of the excipients contained in any of the study drugs used in the trial which may raise contraindications or impact the efficacy of the study drug according to the investigator's judgement
10. Subject has severe, acute or uncontrolled cardiovascular condition (such as but not limited to unstable ischemic heart disease, NYHA Class IV, left ventricular failure, acute myocardial infarction or unstable angina) in the last 6 months
11. An abnormal and clinically significant 12-lead ECG at either the screening or randomization visit.
12. Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug according to investigator's judgement
13. Unstable or uncontrolled concurrent disease which may impact the efficacy or safety of the study drug or the subject's participation in the study according to investigator's judgment
14. Malignancy that has not been in complete remission for at least 1 year or any untreated (e.g. resected for cure) localized carcinomas. For complete list of exclusion criteria see protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in pre-dose morning FEV1 at week 28 (V7)

Secondary endpoints 6

1. Change from baseline in 2-hour post-dose morning FEV1 at week 28 (V7)
2. Rate of moderate and severe COPD exacerbations over 52 weeks of treatment
3. SGRQ response (Decrease from baseline in total score ≥4) at Week 28
4. Incidence of treatment-emergent adverse events (TEAEs), adverse drug reactions (ADRs), serious ADRs, serious AEs (SAEs), severe AEs, TEAEs leading to discontinuation from study drug, and TEAEs leading to death
5. Incidence of treatment-emergent pneumonia
6. Incidence of treatment-emergent major adverse cardiovascular events (MACE).

Investigational products

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

Test 1

Comparator 1

Placebo 1

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 2

Locations

5 EU/EEA countries · 93 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 62 files

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

Application history

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