TRIple in asthMA With uncontRolled pAtient on Medium streNgth of ICS + LABA

NCT02676076 | Completed Phase 3 Results DMC

• 2 other identifiers: CCD-05993AB1-032015-000716-18
• Study Type: interventional
• Target: 1,155
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluate the superiority of CHF 5993 100/6/12.5 µg Pressurised Metered Dose Inhaler (pMDI) (fixed combination of extrafine beclometasone dipropionate (BDP) plus formoterol fumarate (FF) plus glycopyrronium bromide \[GB\]) versus CHF 1535 100/6 µg pMDI (fixed combination of extrafine beclometasone dipropionate (BDP) plus formoterol fumarate \[FF\]), with regard to lung functions parameters and rate of exacerbations as well as safety and health economics outcomes, in adult patients with uncontrolled asthma on medium doses of inhaled corticosteroids in combination with long acting ß2 agonists (LABA).

Conditions

Asthma

Keywords

asthma, anticholinergics, triple combination

Outcome Measures

Primary Outcomes (2)

• 1_Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Week 26

  Change from baseline in pre-dose FEV1 was analysed at Week 26 of treatment. FEV1=Forced expiratory volume in the first second

  Week 0 (pre-treatment, baseline) to Week 26.

• 2_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period

  Asthma exacerbation (events): Moderate AND Severe. Severe: asthma worsening requiring initiation of treatment with systemic corticosteroids for at least 3 days (courses of corticosteroids separated by ≥1 week treated as separate severe exacerbations). Moderate: ≥1 of the following criteria fulfilled and leading to a change in treatment (sustained increase of ≥1 puff of short acting beta 2-agonist \[SABA\] for 2 consecutive days) as shown below: * Nocturnal awakening(s) due to asthma requiring SABA for 2 consecutive nights/increase of ≥0.75 from baseline in daily symptom score on 2 consecutive days; increase from baseline in occasions of SABA use on 2 consecutive days (minimum increase 4 puffs/day); * ≥20% decrease in peak expiratory flow from baseline on at least 2 consecutive mornings/evenings or ≥20% decrease in FEV1 from baseline; * Visit to the ER/trial site for asthma treatment not requiring systemic corticosteroid.

  Week 0 (pre-treatment, baseline) to Week 52.

Secondary Outcomes (29)

• 3_Change From Baseline in Peak(0-3h) FEV1 at Week 26

  Week 0 (pre-treatment, baseline) and Week 26.

• 4_Change From Baseline in Morning Peak Expiratory Flow (PEF) Over the 26-Week Treatment

  Week 0 (pre-treatment, baseline) to Week 26.

• 5_Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period - Pooled Analysis

  The entire treatment period; up to Week 52.

• 6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits

  Week 0 (pre-treatment, baseline) to Week 52.

• 7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits

  Week 0 (pre-treatment, baseline) to Week 52.

Study Arms (2)

CHF 5993 100/6/12.5 µg

EXPERIMENTAL

CHF 5993 100/6/12.5 CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB BDP=Beclometasone Dipropionate bid=Twice daily FF=Formoterol Fumarate GB=Glycopyrronium Bromide

Drug: CHF 5993 100/6/12.5

CHF 1535 100/6 µg

ACTIVE COMPARATOR

CHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF BDP=Beclometasone Dipropionate bid=Twice daily FF=Formoterol Fumarate

Drug: CHF 1535 100/6 µg

Interventions

CHF 1535 100/6 µg DRUG

BDP=Beclometasone Dipropionate 100µg; FF=Formoterol Fumarate 6µg.

CHF 1535 100/6 µg

CHF 5993 100/6/12.5 DRUG

BDP=Beclometasone Dipropionate 100µg; FF=Formoterol Fumarate 6µg; GB=Glycopyrronium Bromide 12.5µg.

CHF 5993 100/6/12.5 µg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of asthma ≥ 1 year and diagnosed before 40 years old
• Uncontrolled asthma with double therapy only on medium doses of Inhaled CorticoSteroid (ICS) in combination with Long-acting beta2 Agonist (LABA) with ACQ-7 (Asthma Control Questionnaire) ≥1.5
• Pre-bronchodilator FEV1 \<80% of the predicted normal value
• Positive reversibility test
• At least 1 documented asthma exacerbation in the previous year

You may not qualify if:

• Pregnant or lactating women
• Diagnosis of Chronic Obstructive Pulmonary Disease (COPD)
• Patients with any asthma exacerbation or respiratory tract infection in the 4 weeks prior screening
• Current or ex-smokers (\>= 10 packs year)
• Any change in dose, schedule or formulation of ICS + LABA combination in the 4 weeks prior screening

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Chiesi Clinical Trial Site 276814

Rostock, Germany

Location

Related Publications (6)

• Virchow JC, Kuna P, Paggiaro P, Papi A, Singh D, Corre S, Zuccaro F, Vele A, Kots M, Georges G, Petruzzelli S, Canonica GW. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials. Lancet. 2019 Nov 9;394(10210):1737-1749. doi: 10.1016/S0140-6736(19)32215-9. Epub 2019 Sep 30.

  PMID: 31582314 RESULT

• Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

  PMID: 36472162 DERIVED

• Orlovic M, Magni T, Lukyanov V, Guerra I, Madoni A. Cost-effectiveness of single-inhaler extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium in patients with uncontrolled asthma in England. Respir Med. 2022 Sep;201:106934. doi: 10.1016/j.rmed.2022.106934. Epub 2022 Jul 19.

  PMID: 35872377 DERIVED

• Papi A, Singh D, Virchow JC, Canonica GW, Vele A, Georges G. Normalisation of airflow limitation in asthma: Post-hoc analyses of TRIMARAN and TRIGGER. Clin Transl Allergy. 2022 Apr 17;12(4):e12145. doi: 10.1002/clt2.12145. eCollection 2022 Apr.

  PMID: 35450196 DERIVED

• Singh D, Virchow JC, Canonica GW, Vele A, Kots M, Georges G, Papi A. Determinants of response to inhaled extrafine triple therapy in asthma: analyses of TRIMARAN and TRIGGER. Respir Res. 2020 Oct 29;21(1):285. doi: 10.1186/s12931-020-01558-y.

  PMID: 33121501 DERIVED

• Singh D, Virchow JC, Canonica GW, Vele A, Kots M, Georges G, Papi A. Extrafine triple therapy in patients with asthma and persistent airflow limitation. Eur Respir J. 2020 Sep 24;56(3):2000476. doi: 10.1183/13993003.00476-2020. Print 2020 Sep. No abstract available.

  PMID: 32430414 DERIVED

Related Links

• Study Record on EU Clinical Trials Register including results.
• Time course of exacerbation reduction with extrafine beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) pMDI in adults with moderate to severe asthma: A post-hoc analysis of the TRIMARAN and TRIGGER Studies
• TRIple in asthMA With uncontRolled pAtient on Medium streNgth of ICS + LABA (TRIMARAN) ClinicalTrials.gov ID NCT02676076
• Study Record on EU Clinical Trials Register including results. Study CCD-05993AB2-02; TRIGGER;
• TRIple in Asthma hiGh strenGth vErsus Ics/ Laba hs and tiotRopium (TRIGGER)

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Clinical Trial Transparency
• Organization: Chiesi Farmaceutici S.p.A.

clinicaltrials_info@chiesi.com

+ 39 0521 2791

Study Officials

• Christian Virchow, MD

  Facharzt für Innere Medizin Rostock, Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2016
• First Posted: February 8, 2016
• Study Start: February 17, 2016
• Primary Completion: May 17, 2018
• Study Completion: May 17, 2018
• Last Updated: June 26, 2026
• Results First Posted: June 26, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Chiesi access criteria and complete process for clinical trial data sharing is available on the Chiesi Group website.

Locations

DE (1)