Step-up to Medium Strength Triple Therapy vs High Strength ICS/LABA in Adult Asthmatics Uncontrolled on Medium Strength ICS/LABA

NCT05018598 | Terminated Phase 4

• 2 other identifiers: CLI-05993AB1-062021-002391-39
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this phase IV Study is to compare the efficacy of CHF5993 (BDP/FF/GB 100/6/12.5 pMDI) on uncontrolled asthma subjects, versus CHF1535 (BDP/FF 200/6 pMDI). The open label extension part aims to assess the proportion of subjects whose asthma remains or becomes adequately controlled..

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• Main phase: Proportion of subjects exhibiting No Persistent Airflow Limitation (NPAL) on average over 26 weeks of treatment in the study sub-population with Persistent Airflow Limitation (PAL) status at screening

  Proportion of subjects exhibiting on average No Persistent Airflow Limitation (NPAL) status over 26 weeks of treatment in the study sub-population meeting Persistent Airflow Limitation (PAL) status at screening. A subject is defined as PAL at screening if post-bronchodilator (salbutamol) FEV1/FVC ratio is \< 0.7. A subject is defined as NPAL during the treatment period if the mean of their 2 hour post-dose FEV1/FVC ratio collected during the treatment period is ≥ 0.7

  Over 26 weeks of treatment

• Open-label extension phase: Proportion of subjects that remains or becomes "Adequately Controlled" at the end of the Open-Label extension phase

  Proportion of subjects that remains or becomes "Adequately Controlled" at the end of the Open-Label extension phase (i.e. Week 50), after the assignment to either MS CHF5993 (BDP/FF/GB 100/6/12.5 pMDI) or HS CHF5993 (BDP/FF/GB 200/6/12.5 pMDI) according to their asthma control status ('Controlled' vs 'Uncontrolled') at the end of MiSTIC main phase (week 26)

  Over 24 weeks of treatment

Secondary Outcomes (1)

• Change from baseline in pre-dose FEV1 at Week 26 in the study sub-population meeting PAL criterion at screening

  Over 26 weeks of treatment

Study Arms (2)

CHF5993 100/6/12.5 μg (main phase and extension phase)

EXPERIMENTAL

Main phase: 2 inhalations BID, Daily dose is 400/24/50 μg x 26 weeks Open-label extension phase: 2 inhalations BID, Daily dose is 400/24/50 μg x 24 weeks

Drug: Administration via pressurized metered dose inhaler (pMDI)

CHF1535 200/6 μg (main phase) / CHF5993 200/6/12.5 μg (extension phase only)

ACTIVE COMPARATOR

Main phase: 2 inhalations BID, Daily dose is 800/24 μg x 26 weeks Open-label extension phase: 2 inhalations BID, Daily dose is 800/24/50 μg x 24 weeks

Drug: Administration via pressurized metered dose inhaler (pMDI)

Interventions

Administration via pressurized metered dose inhaler (pMDI) DRUG

CHF5993 pMDI

CHF5993 100/6/12.5 μg (main phase and extension phase)

Eligibility Criteria

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

You may qualify if:

• Informed consent: Subject's written informed consent obtained prior to any study related procedures;
• Sex and age: Male or female subjects aged ≥ 18 and ≤ 75 years;
• Diagnosis of asthma: A documented diagnosis of persistant asthma for at least 1 year according to GINA recommendations (Box 1-2, GINA report 2021), and with diagnosis before the subject's age of 40 years;
• Stable asthma therapy: a stable treatment with medium dose of Inhaled corticosteroids (ICS) (extrafine BDP daily dose \> 200 and ≤400 µg or estimated clinically comparable dose, as described in GINA 2021 box 3-6) plus a long-acting ß2-agonist (LABA) (formoterol 24 µg or salmeterol 100 µg or vilanterol 25 µg or other approved dose of LABA as clinically comparable to the others) for at least 4 weeks prior to screening;
• Lung function: A pre bronchodilator FEV1 \< 80% of the predicted normal value, after appropriate washout from bronchodilators, at the screening and randomization visits;
• Bronchodilator responsiveness: A demonstrated increase in FEV1 \> 12% and \> 200 mL over baseline within 30 minutes after inhaling 400 µg of salbutamol pMDI (based on ATS/ERS guidelines);
• A Post-bronchodilator FEV1/FVC ratio ≥ 0.5 within 30 minutes after inhaling 400 µg of salbutamol pMDI at screening (based on ATS/ERS guidelines);
• Poor Asthma control: Evidence of poorly controlled or uncontrolled asthma as based on an Asthma Control Questionnaire© (ACQ-7) score ≥ 1.5 at screening and at randomization;
• History of asthma exacerbations: A documented history of one or more asthma exacerbations requiring treatment with systemic corticosteroids or emergency department visit or inpatient hospitalization in the last 3 years prior to screening;
• A willingness and ability:
• to correctly use the pMDI inhalers;
• to perform all trial related procedures including technically acceptable pulmonary function tests;
• to correctly use the e-Diary/e-Peak flow meter.
• Female subjects:
• a. Woman of Childbearing Potential (WOCBP) fulfilling one of the following criteria: i. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up call or ii. WOCBP with non-fertile male partners (contraception is not required in this case).

You may not qualify if:

• Pregnant or lactating woman where pregnancy is defined as the state of a female after conception and until termination of the gestation, confirmed by a positive pregnancy test (serum pregnancy test to be performed at screening visit and urine pregnancy test to be performed prior to randomization);
• Run-in compliance to study drug and e-Diary completion \< 50% at randomization;
• History of "high risk" asthma: History of near fatal asthma or hospitalization for asthma in intensive care unit which, in the judgement of the Investigator, may place the subject at undue risk if enrolled in this study;
• Recent asthma exacerbation: hospitalization, emergency room admission or use of systemic corticosteroids for an asthma exacerbation in the 4 weeks prior to screening visit or during the run-in period;
• Note: Subjects experiencing an exacerbation during the run-in period may be re-screened once, at least 4 weeks after recovery.
• Non-persistent asthma: exercise-induced, seasonal asthma (as the only asthma-related diagnosis) not requiring daily asthma control medicine;
• Subjects using systemic corticosteroid medication in the 4 weeks or slow release corticosteroids in the 12 weeks, prior to screening;
• Asthma requiring use of biologics: Subjects receiving asthma treatment with an injectable biologic drug such as monoclonal antibodies;
• Respiratory disorders other than asthma: Subjects with known respiratory disorders other than asthma. This can include but is not limited to: diagnosis of COPD as defined by the current guidelines (e.g. GOLD Report), known α1-antitrypsine deficiency, active tuberculosis, bronchiectasis, sarcoidosis, interstitial lung diseases, idiopathic pulmonary fibrosis, and pulmonary hypertension;
• Lung cancer or history of lung cancer: Subjects with an active diagnosis of lung cancer or a history of lung cancer;
• Lung resection: Subjects with a history of lung volume resection;
• Respiratory tract infection: Subjects with respiratory tract infection within 4 weeks prior to screening or during the run-in period; Note: Subjects experiencing a respiratory tract infection during the run-in period may be re-screened once, at least 4 weeks after recovery.
• Smoking status: Current smoker or ex-smoker with a smoking history of ≥ 10 pack-years (pack-years = the number of cigarette packs per day times the number of years). Ex- smokers must have stopped smoking for ≥1 year (≥ 6 months for e-cigarettes).
• Cancer or history of cancer (other than lung): Subjects with active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized carcinoma (e.g. basal cell carcinoma, in situ carcinoma of the cervix adequately treated, …) is acceptable;
• Cardiovascular diseases: Subjects who have clinically significant (CS) cardiovascular condition according to Investigator's judgement, such as but not limited to: congestive heart failure (NYHA class IV), unstable or acute ischemic heart disease in the last year prior to screening, history of sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months prior to screening (sustained meant lasting more than 30 seconds or ending only with external action, or led to hemodynamic collapse; non-sustained meant \> 3 beats \< 30 seconds, and or ending spontaneously, and or asymptomatic), high degree impulse conduction blocks (\> 2nd degree atrioventricular block type 2),persistent, long standing or paroxysmal atrial fibrillation (AF); Note: Subjects with permanent AF (for at least 6 months prior screening) with a resting ventricular rate \< 100/min, controlled with a rate control strategy (i.e. selective β blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) can be considered for enrolment;

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Simplex Kft

Nyíregyháza, 4481, Hungary

Location

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

Study Officials

• Kostantinos Kostikas

  Head Respiratory Medicine Department, University Hospital of Ioannina, Greece

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The extension phase will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 24, 2021
• Study Start: February 25, 2022
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)