- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02579850
2-arm Parallel Group Study of Fixed Combination of CHF 5993 vs Ultibro® in COPD Patients (TRIBUTE)
52-week, Double Blind, Randomized, 2 Active Parallel Arms Study of Fixed Combination CHF 5993 Administered vs Ultibro® in COPD Patients
Study Overview
Status
Conditions
Detailed Description
Outpatients attending the hospital clinics/study centres will be recruited. Patients with severe and very severe COPD airflow obstruction according to GOLD 2014 criteria. A total of approximately 2192 patients will need to be screened in order to obtain 1534 (767 per arm) randomized and evaluable patients. Approximately 200 sites will be involved worldwide.
Each patient will perform a total of 8 clinic visits (V0 to V7) during the study.
The Primary objective is to demonstrate the superiority of CHF 5993 pMDI over Ultibro® in terms of moderate and severe COPD exacerbation rate over 52 weeks of treatment.
The Secondary objectives are:
- To evaluate the effect of CHF 5993 pMDI on other lung function parameters, patient's health status and clinical outcome measures;
- To assess the safety and the tolerability of the study treatments.
A 2-week open-label run-in period under Ultibro® followed by a 52-week randomised treatment period.
The trial design will be optimised to measure exacerbation rates by using the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), developed means of collecting patient-reported outcome (PRO) data, which helps to capture the frequency of exacerbations.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Parma, Italy, 43123
- Chiesi Farmaceutici S.p.A.
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion :
- Male and female ≥ 40 years
- Severe or very severe COPD diagnosed for at least 12 months
- 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
- Post-bronchodilator FEV1 < 50% of the predicted normal value and a post-bronchodilator FEV1/FVC ratio < 0.7
- Documented history of at least one exacerbation in the 12 months
Patient under double therapy for at least 2 months prior to screening. Double therapy will be defined by treatment with any of the following:
Orally inhaled corticosteroid (ICS) and (long-acting beta2-agonist) LABA ICS and long-acting muscarinic antagonist (LAMA) Orally LABA and LAMA Monotherapy with LAMA for at least 2 months prior to screening
- Symptomatic patient at screening with a CAT score ≥ 10.
- Cooperative attitude and ability to use correctly the inhalers, the spacer AeroChamber Plus (only to patients who are using a spacer), the electronic devices with COPD questionnaire.
Exclusion :
- Pregnant or lactating women and all women physiologically capable of becoming pregnant UNLESS are willing to use one or more of the reliable methods of contraception
- Patient with a current clinical diagnosis of asthma with a physician-judged need for inhaled or oral corticosteroid therapy
Patient requiring use of the following medications:
Course of systemic steroids > 3 days for COPD exacerbation in the 4 weeks prior to screening Course of antibiotics for COPD exacerbation > 7 days in the 4 weeks prior to screening Phosphodiesterase-4 inhibitor in the 4 weeks prior to screening Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to screening
- COPD exacerbation requiring prescription of systemic corticosteroids and/or antibiotics or hospitalization during the run-in period
- Patient treated with non-cardioselective β-blockers in the month preceding the screening or during the run-in period.
- Patient treated with long-acting antihistamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study or if taken as needed
- Patient requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
- Known respiratory disorders other than COPD which may impact the efficacy of the study drug
- Patient who have clinically significant cardiovascular condition
- Patient with atrial fibrillation (AF): Paroxysmal atrial fibrillation, Persistent, Long standing or Permanent
- Abnormal and clinically significant 12-lead ECG that results in active medical problem which may impact the safety of the patient
- Patient whose ECG shows QTcF >450 ms for males or QTcF >470 ms for females at screening visit are not eligible (not applicable for patient with pacemaker)
- Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction would prevent use of anticholinergic agents
- History of hypersensitivity to M3 Antagonists, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial which may raise contra-indications or impact the efficacy of the study drug
- Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug
- Patients with hypokalaemia (serum potassium <3.5 mEq/L or 3.5 mmol/L) or uncontrolled hyperkalaemia
- Unstable concurrent disease which may impact the results of the study
- Patients with any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next six months (after V1) or with malignancy for which they are currently undergoing radiation therapy or chemotherapy
- History of alcohol abuse or substance/drug abuse within 12 months prior to screening visit
- Participation in another clinical trial if investigational drug was received less than 8 weeks prior to screening visit
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CHF 5993 + Ultibro matched placebo
Fixed triple therapy with BDP/FF/GB 100/6/12.5 mcg (CHF 5993) administered 2 puffs twice daily via pMDI + Fixed combination of indacaterol and of glycopyrronium (Ultibro® Breezhaler®) matched placebo administered once daily via DPI for 52-week treatment. Patient used to take pMDI medication using a spacer will be provided with a new spacer for the study. 7 study visits including : central spirometry tests, Local laboratory, COPD assessment test (visit 1 only), Local laboratory Assessments Saint George's Respiratory Questionnaire EXACT-pro questionnaire |
Active medication treatment CHF 5993 and Ultibro matched placebo administered twice a day
Other Names:
Central spirometry to assess forced expiratory volume at one second and forced vital capacity
COPD assessment test (CAT) at visit 1
ECG + Standard Haematology and Biochemistry
Saint George's Respiratory Questionnaire
daily from randomization (Visit 2) to end of study (Visit 7)
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Active Comparator: Ultibro + CHF 5993 matched placebo
Fixed combination of indacaterol 85 mcg and of glycopyrronium 43 mcg (Ultibro® Breezhaler®) administered once daily via DPI + Fixed triple therapy with BDP/FF/GB (CHF 5993) matched placebo administered 2 puffs twice daily via pMDI for 52-week treatment. Patient used to take pMDI medication using a spacer will be provided with a new spacer for the study. 7 study visits including : central spirometry tests, Local laboratory, COPD assessment test (visit 1 only), Local laboratory Assessments, Saint George's Respiratory Questionnaire, EXACT-pro questionnaire |
Central spirometry to assess forced expiratory volume at one second and forced vital capacity
COPD assessment test (CAT) at visit 1
ECG + Standard Haematology and Biochemistry
Saint George's Respiratory Questionnaire
daily from randomization (Visit 2) to end of study (Visit 7)
Active medication treatment Ultibro and CHF 5993 matched placebo administered twice a day
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Moderate and severe COPD exacerbation rate over 52 weeks of treatment
Time Frame: 1 year
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Exacerbations will be evaluated at each study visit and collected using EXACT-PRO filled-in by patient every day throughout the study
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1 year
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Time to first moderate to severe COPD exacerbation
Time Frame: 1 year
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1 year
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Rate of severe COPD exacerbation over 52 weeks of treatment
Time Frame: 1 year
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1 year
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Rate of moderate COPD exacerbation over 52 weeks of treatment
Time Frame: 1 year
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1 year
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Change from Baseline at each visit and over the entire treatment period in pre-dose morning FEV1
Time Frame: 1 year
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1 year
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Mario Scuri, MD, Chiesi Farmaceutici S.p.A.
- Principal Investigator: Nicolas Roche, Pr, Hopitaux Universitaires Paris Centre - Groupe Hospitalier Cochin
Publications and helpful links
General Publications
- Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, Celli B. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal. Int J Chron Obstruct Pulmon Dis. 2018 Dec 12;13:3971-3981. doi: 10.2147/COPD.S185975. eCollection 2018.
- Singh D, Fabbri LM, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy delays COPD clinically important deterioration vs ICS/LABA, LAMA, or LABA/LAMA. Int J Chron Obstruct Pulmon Dis. 2019 Feb 28;14:531-546. doi: 10.2147/COPD.S196383. eCollection 2019.
- Singh D, Fabbri LM, Corradi M, Georges G, Guasconi A, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy in patients with symptomatic COPD and history of one moderate exacerbation. Eur Respir J. 2019 May 18;53(5):1900235. doi: 10.1183/13993003.00235-2019. Print 2019 May.
- Papi A, Petruzzelli S, Vezzoli S, Georges G, Fabbri LM. Triple therapy for all patients with severe symptomatic COPD at risk of exacerbations. Eur Respir J. 2019 Apr 18;53(4):1900147. doi: 10.1183/13993003.00147-2019. Print 2019 Apr. No abstract available.
- Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, Guasconi A, Montagna I, Vezzoli S, Petruzzelli S, Scuri M, Roche N, Singh D. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018 Mar 17;391(10125):1076-1084. doi: 10.1016/S0140-6736(18)30206-X. Epub 2018 Feb 9. Erratum In: Lancet. 2018 Feb 26;:
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CCD-05993AA1-08
- 2014-001704-22 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Chiesi commits to sharing with qualified scientific and medical Researchers, conducting legitimate research, Patient-level Data, Study-level Data, the Clinical Protocol and the full CSR, providing access to clinical trial information consistently with the principle of safeguarding commercially confidential information and patient privacy. Any shared Patient-level Data is anonymized to protect personally identifiable information.
Chiesi access criteria and complete process for clinical data sharing is available on the Chiesi Group website.
IPD Sharing Access Criteria
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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