Comparison Between CHF5993 pMDI 200/6/12.5 µg HFA-152a VS CHF5993 pMDI 200/6/12.5 µg HFA-134a in Subjects With Asthma (TRECOS). (TRECOS)

A 12-week Double-blind, Multicentre, Randomised, Active-controlled, 2-arm, Parallel-group Clinical Trial to Evaluate the Safety of CHF5993 pMDI 200/6/12.5 μg HFA-152a, Compared to CHF5993 pMDI 200/6/12.5 μg HFA-134a, in Subjects With Asthma.

The CLI-05993AB6-03 Study is an interventional study designed to investigate the safety and efficacy of a new low global warming potential propellant (HFA-152a) compared to the currently approved one (HFA-134a) in the medication (CHF5993) in patients with moderate to severe asthma

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: CHF5993 200/6/12.5 μg pMDI HFA-152a; Drug: Inhaler CHF5993 200/6/12.5 μg pMDI HFA-134a

Detailed Description

Outpatients attending the hospital clinics/study centers will be recruited. Moderate to severe controlled asthma adult subjects will be recruited. A total of 513 subjects will be randomised. The whole study will last approximately 16 weeks for each subject.

• Study Type: Interventional
• Enrollment (Actual): 827
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria
    • "IPSMCPP-D-R Veleva" EOOD
  • Kozloduy, Bulgaria
    • Medical Center "Zdrave -1"
  • Momchilgrad, Bulgaria
    • "AIPSMP Yuskyan Aliosman" Ltd
  • Rousse, Bulgaria, 7000
    • Ambulatory for Specialized Outpatient Medical Care - Individual Practice
  • Rousse, Bulgaria, 7002
    • Specialized Hospital For Active Treatment Of Pneumo-Phthisiatric Diseases Dr. Dimitar Gramatikov - Ruse Ltd.
  • Rousse, Bulgaria, 7002
    • Specialized Hospital For Active Treatment Of Pneumo-Phthisiatric Diseases Dr. Dimitar Gramatikov
  • Shumen, Bulgaria, 9700
    • Multiprofile Hospital For Active Treatment - Shumen AD,
  • Sliven, Bulgaria
    • MHAT Sliven to MMA Sofia
  • Sliven, Bulgaria, 8801
    • Diagnostic Consultative Centre 1-
  • Sofia, Bulgaria, 1680
    • Diagnostics and Consultation Center Convex EOOD
  • Sofia, Bulgaria, 1142
    • University First Multiprofile Hospital for Active Treatment -Sofia "St. Joan Krastilel" EAD
  • Sofia, Bulgaria, 1233
    • Multiprofile Hospital For Active Treatment "Knyaginya Klementina" Sofia EAD,
  • Sofia, Bulgaria, 1510
    • Medical Center Hera EOOD, 20 Klisura str., fl. 2,
  • Sofia, Bulgaria, 1618
    • Multi-profile Hospital for Active Treatment Zdraveto 2012 Ltd.,
  • Sofia, Bulgaria
    • "Medical Center Sun i Zdrave"
  • Sofia, Bulgaria
    • Medical Center "Syrtuin" Ltd
  • Stara Zagora, Bulgaria, 6003
    • Medical Center "New Rehabilitation Center" Ltd
  • Varna, Bulgaria, 9000
    • ASMP MC Kissiovi Ltd.
• Czechia
  • Brno, Czechia, 618 00
    • Hornmed, s.r.o
  • Jihlava, Czechia, 586 01
    • Nemocnice Jihlava, Plicní oddělení
  • Jindřichův Hradec, Czechia, 37701
    • MediTrial s.r.o.
  • Prague, Czechia, 140 00
    • Pneumology dpt., Poliklinika Budějovická, MEDICON a.s.
  • Prague, Czechia, 14000
    • Pneumology dpt., Fakultní Thomayerova nemocnice
  • Prague, Czechia, 190 00
    • Prvni plicni ambulance s.r.o
  • Teplice, Czechia, 415 01
    • Plicni stredisko Teplice s.r.o.
• Georgia
  • Gardabani, Georgia
    • Geo Hospitals Gardabani Multiprofile Medical Centre
  • Gurjaani, Georgia
    • Geo Hospitals Gurjaani Multiprofile Medical Centre
  • Sagarejo, Georgia
    • Geo Hospitals Sagarejo Multiprofile Medical Centre
  • Samtredia, Georgia
    • Medihelp Ltd
  • T'erjola, Georgia, 2400
    • Imermedi-Imereti Regional Medical Center. (Terjolamedi) Ltd.
  • Tbilisi, Georgia, 0114
    • Curatio, Jsc
  • Tbilisi, Georgia, 0144
    • Geo Hospitals Tbilisi Multiprofile Medical Center
  • Tbilisi, Georgia, 0180
    • First Medical Center LLC
  • Zestaponi, Georgia
    • GEO HOSPITALS Zestaphoni Ambulatory Centre
• Germany
  • Berlin, Germany, 10787
    • Klinische Forschung Berlin
  • Berlin, Germany, 10119
    • Studienpraxis Berlin-Brandenburg Cornelia Seelbinder Und Lennart Schaper GbR
  • Berlin, Germany, 10717
    • Lungenpraxis Hohenzollerndamm
  • Berlin, Germany, 12157
    • Policum Berlin Studien GmbH Friedenau
  • Berlin, Germany, 12159
    • Institut für Allergie- und Asthmaforschung
  • Bonn, Germany, 53119
    • Dr. med. Thomas Ginko Facharzt für Lungen- und Bronchialheilkunde
  • Duisburg, Germany, 47057
    • Neudorfer Lungenpraxis
  • Frankfurt, Germany, 60596
    • IKF Pneumologie Frankfurt Clinical Research Centre Respiratory Medicine IFS - Interdisziplinäres Facharztzentrum
  • Fürstenwalde, Germany, 15517
    • Athanasios Xanthopoulos Praxis für Pneumologie
  • Leipzig, Germany, 04299
    • Praxis Für Pneumologie Und Allergologie
  • Leipzig, Germany, 04347
    • POIS Sachsen GmbH
  • Lübeck, Germany, 23552
    • KLB Gesundheitsforschung Lubeck GmbH
  • Magdeburg, Germany, 39120
    • SMO Zentrum für klinische Studien
  • München, Germany, 12159
    • Pneumologisches Studienzentrum München
  • Schleswig, Germany, 24837
    • Siteworks Prüfzentrum Schleswig GmbH
  • Witten, Germany, 58452
    • Lungenpraxis Witten
• Greece
  • Thessaloniki, Greece, 570 10
    • "George Papanikolaou" General Hospital of Thessaloniki
• Hungary
  • Debrecen, Hungary
    • University of Debrecen, Infectology Clinic Pulmonary unit
  • Gödöllő, Hungary, H-2100
    • Erzsebet Gondozohaz
  • Hatvan, Hungary, H-3000
    • BKS Research Kft.,
  • Nyíregyháza, Hungary, H-4400
    • Revamed Kft
  • Pécs, Hungary
    • INFER-MED Kft
  • Szombathely, Hungary, H-9700
    • Árkádia Egészségközpont
• Italy
  • Genova, Italy, 16132
    • Clinica Malattie Respiratorie e allergologia IRCCS Ospedale Policlinico San Martino
  • Messina, Italy, 98125
    • University of Messina, Allergy and Clinical Immunology Unit, Department of Experimental and Clinical Medicine
  • Naples, Italy, 80131
    • Azienda Ospedaliera dei Colli - Ospedale Monaldi
• Netherlands
  • Almere Stad, Netherlands, 1311 RL
    • EB FlevoResearch BV
  • Breda, Netherlands, 4818 CK
    • Amphia Hospital
  • Zutphen, Netherlands, 7207 AE
    • Gelre Hospitals Zutphen (Gelre ziekenhuizen Zutphen)
• Poland
  • Bialystok, Poland, 15-010
    • Prywatny gabinet internistyczno-alergologiczny prof. Zenon Siergiejko
  • Bialystok, Poland, 15-044
    • Centrum Medycyny Oddechowej, Mróz Spółka Jawna
  • Bialystok, Poland, 15-276
    • Uniwersytet Medyczny w Bialymstoku Wydzial Nauk o Zdrowiu Klinika Alergologii i Chorób Wewnetrznych
  • Bialystok, Poland, 15-430
    • Prywatna praktyka lekarska. Gabinet pediatryczno - alergologiczny
  • Bydgoszcz, Poland, 85-079
    • Vitamed Galaj I Cichomski Sp. J.
  • Krakow, Poland, 31-011
    • Centrum Nowoczesnych Terapii "Dobry Lekarz"
  • Krakow, Poland, 31-455
    • Private Health Care MEDYK-KRAK Sp. o.o.
  • Krakow, Poland, 31-559
    • Diamond Clinic Spółka z ograniczoną odpowiedzialnością
  • Krakow, Poland, 31-624
    • Małopolskie Centrum Alergologii sp. z o.o.
  • Krakow, Poland, 35-159
    • ATOPIA Niepubliczny Zakład Opieki Zdrowotnej
  • Lodz, Poland, 90-153
    • Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego
  • Maków Podhalański, Poland, 34-220
    • Makowskie Centrum Medyczne MCM "Hamernia" Maków Podhalański
  • Ostrowiec Świętokrzyski, Poland, 27-400
    • Ostrowieckie Centrum Medyczne Spółka Cywilna Anna Olech-Cudzik, Krzysztof Cudzik
  • Rzeszów, Poland, 35-051
    • Prywatny Gabinet Lekarski Małgorzata Pawlukiewicz
  • Skierniewice, Poland, 96-100
    • Clinmedica Research Sp. Z O.O.
  • Sosnowiec, Poland, 41-205
    • PULMAG Grzegorz Gąsior, Marzena Kociołek spółka cywilna
  • Strzelce Opolskie, Poland, 47-100
    • Centrum Medyczne Lucyna i Andrzej DymeK
  • Tarnów, Poland, 33-100
    • ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o.
  • Warsaw, Poland, 41-100
    • CLINICAL BEST SOLUTIONS Fiutkowski Sp. z o.o.
  • Wroclaw, Poland, 51-162
    • Centrum Badan Klinicznych
  • Wroclaw, Poland, 53-301
    • Michał Bogacki Dobrostan
  • Wroclaw, Poland, 54-239
    • Lekarze Specjaliści - J. Małolepszy I Partnerzy
• Romania
  • Bragadiru, Romania, 769764
    • Angisan Grup Srl
  • Bucharest, Romania
    • Medsana Bucharest Medical Center Srl
  • Bucharest, Romania, 011025
    • Centrul Medical Sana (SANA S.R.L.)
  • Bucharest, Romania, 050159
    • National Institute of Pneumology Marius Nasta
  • Cluj-Napoca, Romania, 400332
    • Spitalul Clinic de Pneumoftiziologie Leon Daniello
  • Cluj-Napoca, Romania, 400394
    • Spitalul Clinic de Pneumoftiziologie Leon Daniello
  • Constanța, Romania, 900002
    • Spitalul clinic de Pneumoftiziologie Palazu Mare Constanta
  • Craiova, Romania, 200515
    • Spitalul Clinic de Boli Infecțioase și Pneumoftiziologie "Victor Babeș" Craiova
  • Oradea, Romania
    • Spital Judetean de Urgenta Bihor
  • Timișoara, Romania
    • Clinical Hospital Of Infectious Diseases And Pneumophysiology Dr.Victor Babes Timisoara
  • Timișoara, Romania
    • Clinical Hospital of Infectious Diseases and Pneumophysiology
• Serbia
  • Belgrade, Serbia
    • Municipal Institute for lung diseases and tuberculosis
  • Belgrade, Serbia, 11000
    • Clinic for Pulmonary Diseases, University Clinical center of Serbia
  • Kamenica, Serbia, 21204
    • Institute for Pulmonary Diseases of Vojvodina.
  • Kragujevac, Serbia, 34000
    • Clinic for Pulmonology, University Clinical Center Kragujevac.
  • Kragujevac, Serbia
    • Clinic for Pulmonology, University Clinical Center Kragujevac
  • Niš, Serbia, 18000
    • Clinical Centre of Niš Clinic for Lung Diseases
  • Užice, Serbia, 31000
    • Užice General Hospital Miloša Obrenovića 17.
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Poliklinika ČK PLUS Alian s.r.o
  • Dunajská Streda, Slovakia, 929 01
    • Pľucna ambulancia MUDr. Miroslava Undesser
  • Michalovce, Slovakia, 071 01
    • Nemocnica s poliklinikou Š. Kukuru Michalovce
  • Spišská Nová Ves, Slovakia, 05201
    • Pľúcna ambulacia - MUDr. Slavomír Hrebenár
  • Žilina, Slovakia, 010 01
    • IMUNOALERGOLÓGIA JZ, s.r.o.
  • Žilina, Slovakia, 010 01
    • KOMA Kardioprax, s.r.o.
• Spain
  • Castellon, Spain, 12004
    • Hospital General Universitario de Castellon
  • Girona, Spain, 17003
    • Giromed Institute Parc Científic i Tecnològic Universitat de Girona
  • Madrid, Spain, 28041
    • Hospital Universitario 12 De Octubre
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario de Santiago Hospital Clínico Universitario de Santiago
• United Kingdom
  • Bradford, United Kingdom, BD9 6RJ
    • Bradford Teaching Hospitals NHS Foundation Trust
  • London, United Kingdom, EC1M6BQ
    • Queen Mary University of London
  • London, United Kingdom, UB9 6JH
    • Guy's & St Thomas'NHS Foundation Trust of Royal Brompton Hospital
  • Manchester, United Kingdom, M23 9QZ
    • Medicines Evaluation Unit, Langley Building, Wythenshawe Hospital
  • Portsmouth, United Kingdom, PO6 3LY
    • Portsmouth Hospitals University NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject's written informed consent obtained prior to any study related procedure;
• Male and female adults aged ≥ 18 and ≤ 75;
• Body mass index (BMI) within the range of 18.0 to 35.0 kg/m2 inclusive;
• Non-smokers or ex-smokers who smoked < 10 pack-years (pack-years = the number of cigarette packs per day x the number of years) and stopped smoking > 1 year (6 months for e-cigarettes) prior to screening;
• Diagnosis of asthma: physician-diagnosed asthma for at least
• 6 months and with diagnosis before the age of 50 years;
• Stable asthma therapy: a stable treatment with medium/high doses of inhaled corticosteroids (ICS) + long-acting β-agonist (LABA) + long-acting muscarinic antagonist (LAMA) (fixed or free combination) or medium/high doses of ICS+LABA (fixed or free combination) for at least 4 weeks before screening (medium and high-dose ICS defined as BDP non-extrafine > 500-1000 μg and > 1000 μg respectively, or estimated clinical comparable dose).
• Subjects must have a cooperative attitude and the ability to be trained to use correctly the pMDI inhalers and e-Diary, to be able to read/write, to be able to perform the required outcomes measurements (e.g., technically acceptable spirometry, e-Diary completion) and the ability to understand the risks involved.

Exclusion Criteria:

• History of near fatal asthma, hospitalisation for asthma in intensive care unit which in the judgement of the Investigator may place the subject at undue risk, emergency room access for asthma in the previous 6 months before enrolment;
• Asthma exacerbation requiring systemic corticosteroids (SCS) or emergency room admission or hospitalisation within 4 weeks prior to study entry and/or during the run-in period (to be checked again prior to randomisation);
• Non-permanent asthma: exercise-induced, seasonal asthma (as the only asthma-related diagnosis) not requiring daily asthma control medecine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inhaler CHF5993 200/6/12.5 μg pMDI HFA-152a; Active ingredients: BDP/FF/GB 200/6/12.5 μg per actuation; Excipients: HFA-152a propellant.	Drug: CHF5993 200/6/12.5 μg pMDI HFA-152a; Pressurised Metered Dose Inhaler-2 inhalations twice daily; Other Names: HFA-152a propellant
Active Comparator: Inhaler CHF5993 200/6/12.5 μg pMDI HFA-134a; Active ingredients: BDP/FF/GB 200/6/12.5 μg per actuation; Excipients: HFA-134a propellant.	Drug: Inhaler CHF5993 200/6/12.5 μg pMDI HFA-134a; Pressurised Metered Dose Inhaler-2 inhalations twice daily; Other Names: HFA-134a propellant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change from pre-dose Forced Expiratory Volume in one second with (FEV1) (Safety Assessment to evaluate of the potential bronchoconstriction of the study treatment)	Relative change from pre-dose in FEV1 at the 10 min post-dose timepoint	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To complete the evaluation of FEV1 and the potential for bronchoconstriction of the study treatment (relative change from pre-dose FEV1)	Relative change from pre-dose in FEV1 at all the post dose timepoints	Day 1, Day 7, Week 4, Week 12
To complete the evaluation of FEV1 and the potential for bronchoconstriction of the study treatment (absolute change from pre-dose FEV1)	Absolute change from pre-dose in FEV1 at all post-dose timepoints	Day 1, Day 7, Week 4, Week 12
To complete the evaluation of FEV1 and the potential for bronchoconstriction of the study treatment (number and percentage of subjects with a relative decrease from pre-dose in FEV1)	Calculation of number and percentage of subjects with a relative decrease from pre-dose in FEV1 at each post-dose timpoint and at any post -dose timepoint > 15%	Day 1, Day 7, Week 4, Week 12
To complete the evaluation of FEV1 and the potential for bronchoconstriction of the study treatment (Absolute and relative changes from baseline in pre-dose FEV1)	Absolute and relative changes from baseline in pre-dose FEV1 at all clinical visits	Day 1, Day 7, Week 4, Week 12
To complete the evaluation of FEV1 and the potential for bronchoconstriction of the study treatment (Change from pre-dose in FEV1)	Change from pre-dose in FEV1 AUC 0-2h	Day 1, Day 7, Week 12
Peak expiratory flow (PEF) change from baseline at each inter-visit period over the entire treatment period	Change from baseline at each inter-visit period and over the entire treatment period in morning and evening PEF	Inter-visit, over the entire 12 weeks treatment period
Percentage of days without intake of rescue medication.	Change from baseline at each inter-visit period and over the entire treatment period in the percentage of days without intake of rescue medications	Inter-visit, over the entire 12 weeks treatment period
Change in the average daily use of rescue medication.	Change from baseline at each inter-visit period and over the entire treatment period in the average daily use of rescue medication (number of inhalations/day)	Inter-visit, over the entire 12 weeks treatment period
Change on the average daily asthma symptoms.	Change from baseline at each inter-visit period and over the entire treatment period in the average daily symptoms. Patients are asked to complete daily a questionnaire to collect this information and allow their asthma symptoms to be monitored.	Inter-visit, over the entire 12 weeks treatment period
Change from baseline in Asthma Control Questionnaire 7 (ACQ 7) score.	ACQ 7 is a one week recall questionnaire including 6 questions to be completed by patients on a 7-points scale (0=no impairment, 6= maximum impairment) and 7th point capturing the FEV1 % predicted value (also scoring on a 7-point scale). Questions are equally weighted and the ACQ score is the mean of the 7 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).	At each planned on site study visit, during the entire 12 weeks treatment period.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the safety and tolerability of CHF5993 pMDI HFA-152a in terms of Adverse Events (AEs) / Adverse Drug Reactions (ADRs).	Number and percentage of subjects experiencing AEs, number and percentage of subjects experiencing at least one ADR and number and percentage of subjects experiencing at least one Treatment Emergent Adverse Events (TEAEs)	Through study completion, an average of 1 year
To measure the safety and tolerability of CHF5993 pMDI HFA-152a in terms of number of Adverse Events (AEs) of particular interest.	Number of AEs for each of the following event: cough, dysphonia, paradoxical bronchospasm, hypersensitivity reactions, severe asthma Exacerbations	Through study completion, an average of 1 year
To measure the safety and tolerability of CHF5993 pMDI HFA-152a in terms of incident rate of Adverse Events (AEs) of particular interest.	Incident rate for each of the following AE of particular interest: cough, dysphonia, paradoxical bronchospasm, hypersensitivity reactions, severe asthma Exacerbations.	Through study completion, an average of 1 year
To measure the safety and tolerability of CHF5993 pMDI HFA-152a in terms of rate ration of Adverse Events (AEs) of particular interest.	Rate ratio between treatments for each of the following AE of particular interest: cough, dysphonia, paradoxical bronchospasm, hypersensitivity reactions, severe asthma Exacerbations.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Dave Singh, MD, Medicines Evaluation Unit, Langley Building, Wythenshawe Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Actual): February 18, 2025
• Study Completion (Actual): February 24, 2025

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Norflurane
• Other Study ID Numbers: CLI-05993AB6-03; 2023-503333-22-00 (Other Identifier: EMA CTIS); 17142179 (Other Identifier: ISRCTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No