Fixed Triple Inhaled Combination in Asthmatic Patients in a Real-life Setting (STRENGTH)

A Prospective Non-Interventional Real-world Study Assessing the Effectiveness of Extrafine BDP/FF/G HS Single Inhaler Triple Therapy (SITT) on Symptom Scores in Asthma Patients After 6 Months Treatment

The mainstay of asthma treatment are ICSs, mostly combined with LABA. In the past decade LAMA had been accepted as an add-on treatment for patients at GINA steps 4 and 5. Recently, RCTs proved the efficacy and safety of fixed triple combinations of moderate and high dose of ICS and LABA, LAMA in a very selected asthmatic population, resulting in the market authorisation of these products. However, there is a lack of evidence on the real-world effectiveness of these therapies, especially with regards to improvement in symptom scores and adherence.

Study design Multicentre, national, non-interventional, prospective study evaluating the effectiveness of Trimbow 172/5/9 μg pMDI on symptom scores in 6 months after switch from previous LABA-high dose ICS containing treatment in asthmatics.

Dosage regimen and administration Name of the product: Trimbow 172 micrograms/5 micrograms/9 micrograms pressurised inhalation, solution (henceforth abbreviated as Trimbow 172/5/9 µg pMDI) . Each delivered dose (the dose leaving the mouthpiece) contains 172 µg of beclometasone dipropionate, 5 µg of formoterol fumarate dihydrate and 9 µg of glycopyrronium (as 11 µg glycopyrronium bromide). Each metered dose (the dose leaving the valve) contains 200 µg of beclometasone dipropionate, 6 µg of formoterol fumarate dihydrate and 10 µg of glycopyrronium (as 12.5 µg glycopyrronium bromide). The recommended dose is two inhalations twice daily. The maximum dose is two inhalations twice daily.

1. AIM OF THE STUDY (research objective)

   Primary objective:

   The main objective is to assess the effectiveness of BDP/FF/G 172/5/9 μg fixed triple combination in a real-world setting, with regards to improvements in symptom scores (ACT).

   Primary outcome measures:

   • Change (improvement) of ACT score, during the 6 months of treatment (Visit 3), compared to the score at baseline.
   • The percentage of patients achieving an improvement in ACT score of 3 points (MCID, minimum clinically important difference) or more, after the 6 months treatment (Visit 3) compared to baseline.

   Secondary objectives:

   Secondary objectives are the assessments of improvement in lung function and adherence to treatment.

2. TEST SAMPLE AND METHOD, RECRUITMENT PRINCIPLE No patient recruitment will be performed. Eligible patients will be enrolled during their regular asthma management with participating physicians after giving their written informed consent. Patient inclusion will take place among patients having severe asthma and attending pulmonology outpatient clinics (the chosen study sites are attached as annexes to the study protocol), strictly at the time of the patient's visit. The planned number of patients is 200.

3. STRUCTURE OF THE STUDY In accordance with the requirements of non-interventional studies, the assignment of patients to Trimbow 172/5/9 μg pMDI therapy should be made independently of the study, and patients should only be considered for inclusion in the study after a prior therapeutic decision has been made by a pulmonologist. Patient enrolment can take place after the patient has been fully informed about the purpose of the study and all of its details, and the patient has read and signed the patient information leaflet and patient consent form, including any questions they may have. Once this has taken place, the data that would have been generated anyway during the outpatient examination of the patient in accordance with daily practice can be recorded. This is considered the first visit of the study (Visit 1). During this visit, the patient's main demographic data, information on comorbidities and concomitant medications, previous and current asthma therapies, asthma specific assessment (including ACT), exacerbation history, post-dose lung function values (if spirometry data is available), laboratory results (if a laboratory test is performed), maintenance and reliever inhaled therapies (former and new), and adherence to therapy based on Test of Adherence to Inhalers (TAI-12) questionnaire are recorded. Patients will then attend two additional visits 30 days and 6 months after enrolment as per routine clinical practice (Visits 2 and 3). During these visits, data will also be recorded, once again, according to routine clinical practice.

   If the patient's maintenance therapy changes during the study as decided by the treating pulmonologist, and the patient is no longer receiving Trimbow 172/5/9 μg pMDI, the patient will be automatically excluded from this NIS. The fact of the therapy modification and its exact date must be recorded on the "current medication" form in the eCRF (electronic Case Report Form) of the next visit. If the change in therapy is related to a suspected adverse reaction, it should be reported separately on the eCRF platform in accordance with respective section of this protocol.

   This NIS is open to all eligible patients according to the inclusion and exclusion criteria. Permitted concomitant treatments: allowed all medications according to local clinical practice (any non-inhalation therapy for asthma or other diseases) and reliever (short-acting bronchodilators) inhaled therapies for asthma.

4. START AND DURATION OF THE STUDY The first patient enrolment will take place after receiving approval from the Agency for Medicinal Products and Medical Devices of the Republic of Slovenia, based on a beneficial assessment of the National Medical Ethics Committee of the Republic of Slovenia. The study is planned to start in November 2024. Accordingly, first patient first visit (FPFV) is also planned to take place in November, 2024. Study sites will have 12 months to enrol patients. After the last visit of the last patient (LPLV), centres will have one month to collect all missing data / correct any data flagged as queries during monitoring. The LPLV is expected to take place in June 2026.

5. STUDY PLAN A total of 3 visits will be performed for the assessment of the primary and secondary endpoints during the study. Patient may be enrolled in the study and their data may only be recorded, if these data would also have been recorded in accordance with standard medical practice.

   • Visit 1: Time of enrolment - a normal visit, according to routine clinical practice. Informed consent and baseline patient characteristics will be collected.
   • Visit 2: 1 month after enrolment (± 2-3 days)
   • Visit 3: 6 months after enrolment (± 5-7 days)

INCLUSION CRITERIA:

• Physician-confirmed clinical diagnosis of asthma according to GINA guidelines and treated for at least 3 years before inclusion

• Patients ≥ 18 years of age in ambulatory care

• Uncontrolled asthma according to the physician's clinical assessment despite the use of:

  1. LABA and high dose ICS or
  2. LABA and high-dose ICS + LAMA multi-inhaler triple therapy for a minimum of three months.

• Patients who are eligible for the use of Trimbow 172/5/9 μg pMDI according to the SmPC :

  1. at least on exacerbation, requiring systemic (oral or intravenous) corticosteroids in the previous 12 months
  2. uncontrolled asthma (ACT≤15) or partially controlled asthma (15<ACT<20)
  3. FEV1<80% at baseline

• Inhaled asthma therapy was changed to Trimbow 172/5/9 μg pMDI no more than 1 week prior to OR on the day of study inclusion

• Patient provided written, informed consent to study participation

EXCLUSION CRITERIA:

• Participation in any clinical trial within 30 days prior to enrolment
• Patients hospitalized due to an exacerbation of their asthma within the last 4 weeks prior to enrolment
• Another respiratory condition, apart from asthma or COPD, that may interfere with the effectiveness of the treatment studied AND/OR another important clinical situation that may interfere with patient's compliance with the treatment.
• Continuous use of oral (>5 mg prednisolone/day OR >4 mg methylprednisolone/day) OR intravenous corticosteroids
• Use of continuous oxygen therapy
• Any malignant disease in the last 5 years
• Tuberculosis (active or anamnestic)
• Actual or previous use of biologics for asthma treatment in the past 12 months
• All exclusion criteria listed in Trimbow 172/5/9 μg pMDI SmPC