The primary objective of this study is to demonstrate the effectiveness of the DS compared to the SoC group. The secondary objectives:(#1) is to describe the asthma management actions by HCPs for all patients in both groups. (#2) is to evaluate…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the proportion of patients for the DS and SoC groups
achieving well-controlled asthma as defined by an ACT score of greater than or
equal to 20, or a clinically important improvement in asthma control as defined
by an increase of at least 3 ACT units from baseline at the end of the 24-week
treatment period.
Secondary outcome
(#1)
This secondary endpoint is the frequency of clinically driven assessments and
types of interventions done to improve asthma control including:
• number of discussions regarding inhaler technique
• number of discussions regarding adherence
• number of adjustments of therapy including:
- changes to current inhaler therapy (stepping up and stepping down)
- change to different inhaled medication
- additional inhaled medication
- addition of a systemic corticosteroid medication for asthma or
another controller, including LAMA or biologics
• frequency of intervention to manage comorbid conditions associated with poor
asthma control (gastroesophageal reflux disease, sinusitis, etc.)
(#2)
This secondary endpoint is the change from baseline in adherence to the BF
Digihaler DS when prescribed as maintenance treatment, defined as the
proportion of actual inhalation doses taken out of the total number of
inhalation doses prescribed over the 24-week treatment period.
(#3)
This secondary endpoint is the change from baseline measured by the WPAI
questionnaire, completed by patients in both groups, at baseline and at the end
of the 24-week treatment period.
(#4)
This secondary endpoint is the assessment of the DS (BF Digihaler, App, DHP
[Cloud solution], and HCP-facing dashboard) acceptability and usability,
utilizing the SUS completed by the patients in the DS group and the
investigational center personnel at the End of treatment visit.
(#5)
This secondary endpoint is the reporting of adverse events related to BF
Digihaler DS at participating investigational centers.
The safety endpoints for this study include the following for all patients in
both groups:
• adverse event data
• adverse device effect data
Background summary
1. INTRODUCTION AND BACKGROUND INFORMATION
1.1. Introduction
Asthma is a heterogeneous disease usually characterized by chronic airway
inflammation and defined by the history of respiratory symptoms that vary over
time and in intensity (Global Initiative for Asthma [GINA] 2021). These asthma
symptoms may be associated with suboptimal treatment or aging, may lead to
chronic changes in airway structure and function, increasing the morbidity and
mortality of those affected (Global Initiative for Asthma [GINA] 2021).
GINA includes maintenance and reliever therapy (MART) with low-dose ICS
formoterol as the preferred treatment for asthma that remains uncontrolled
despite good adherence and inhaler technique, based on evidence of reduced
exacerbations compared with the same dose ICS-long acting beta2 agonist (LABA)
or higher dose ICS used as maintenance and a SABA as rescue.
Budesonide is a potent synthetic glucocorticosteroid with potent anti
inflammatory activity. Inflammation is an important component in the
pathophysiology of asthma, and corticosteroids have been shown to inhibit
multiple inflammatory cells and mediators involved in the pathophysiology of
asthma. Formoterol is a potent, selective LABA producing relaxation of
bronchial smooth muscle in patients with reversible airway obstruction. The
pharmacologic effects of beta2 adrenoceptor agonist drugs, including
formoterol, are at least in part attributable to stimulation of intracellular
adenyl cyclase that leads to increased levels of cyclic 3*,5* adenosine
monophosphate (cyclic AMP), which causes relaxation of bronchial smooth muscle
and inhibition of release of mediators of immediate hypersensitivity from
cells, especially from mast cells.
Teva Branded Pharmaceutical Products R&D, Inc. (Teva) has developed a
budesonide/formoterol fumarate dihydrate (BF) multidose dry powder inhaler with
an integrated electronic module as a next-generation inhaler solution for
patients with asthma and chronic obstructive pulmonary disease (COPD). The
investigational product, BF Digihaler, delivers a dose of BF equivalent to
DUORESP SPIROMAX® and adds electronic capabilities ultimately intended to
provide patients with feedback to potentially improve inhalation technique,
disease understanding, management, and outcomes.
In this study, BF will be delivered via a Digihaler. The system is an inhaler
with integrated data logger capable of storing and transmitting timestamped
data. The information from the BF Digihaler will be transmitted wirelessly
(Bluetooth Low Energy) to the mobile phone App. From the App, with the
patient*s informed consent, data may be transmitted to the Digital Health
Platform (DHP; Cloud solution) and then to a Healthcare professional
(HCP)-facing dashboard. The DHP is used to provide patient-specific data to the
patient*s healthcare professional (HCP) via the dashboard, a secure web
interface. The following devices will be evaluated in this study:
• Budesonide/formoterol (BF) Digihaler Digital System (DS) with 4 component
devices:
- Device 1: BF Digihaler used as both MART
- Device 2: Patient-facing mobile phone application (App)
- Device 3: DHP (Cloud solution)
- Device 4: HCP-facing dashboard
The purpose of the study is to evaluate whether outcomes for patients using the
BF Digihaler DS as MART can be optimized better than a Standard of Care (SoC)
group who will be treated with their current treatment prescribed by the
investigational center based on asthma guidelines and clinician judgement and
will not use the DS during the treatment period. The study will also assess
adherence patterns to maintenance treatment (BF Digihaler) in the BF Digihaler
DS group and the asthma management actions of HCPs using the dashboard as part
of the DS and will collect information from patients and investigational center
personnel questionnaires on system usability, quality of life, and work
productivity.
1.2. Findings from Nonclinical and Clinical Studies
The pharmacology and safety profile of BF Digihaler have been well established.
Refer to the DUORESP SPIROMAX summary of product characteristics (SmPC) for
relevant BF Digihaler (budesonide and formoterol) inhalation powder nonclinical
safety information.
Teva*s BF SPIROMAX has been evaluated in 15 completed clinical studies in over
2141 subjects (720 healthy adult volunteers, 605 asthmatic adolescents and
adults, 739 asthmatic adults, and 77 pediatric subjects). The results from
these studies evaluating the doses of 160/4.5 mcg and 320/9 mcg are included in
the DUORESP SPIROMAX SmPC.
1.3. Known and Potential Benefits and Risks to Patients
The investigational product, BF Digihaler, delivers a dose of BF equivalent to
DUORESP SPIROMAX and adds electronic capabilities intended to provide patients
with feedback to potentially improve inhalation technique, disease
understanding, management, and outcomes. The addition of the integrated
electronic module has no impact on the pharmaceutical performance of the BF
Digihaler relative to BF SPIROMAX, and it does not affect the user steps
required to take a dose (performance and functional testing on file at Teva).
Additional information regarding benefits and risks of BF Digihaler to patients
may be found in the Investigator*s Brochure (IB).
Study objective
The primary objective of this study is to demonstrate the effectiveness of the
DS compared to the SoC group.
The secondary objectives:
(#1) is to describe the asthma management actions by HCPs for all patients in
both groups.
(#2) is to evaluate adherence patterns to maintenance treatment (BF Digihaler)
in the DS group.
(#3) is to evaluate work productivity and activity impairment in asthma
patients in both groups.
(#4) is to assess the usability and acceptability of the DS by patients in the
DS group and the investigational center personnel.
(#5) is to evaluate the safety of BF Digihaler DS.
Study design
3. STUDY DESIGN
3.1. General Study Design and Study Schematic Diagram
This is a 24-week treatment, multicenter, open-label, randomized, parallel
group comparison study of SoC treatment versus the BF Digihaler DS, including
inhaler, App, DHP (Cloud solution), and HCP-facing dashboard, to optimize
outcomes in adult patients with asthma.
The study will consist of a screening/baseline visit (Visit 1), a 24-week,
open-label treatment period with Visit 2 at week 12, Visit 3 at week 24, and a
follow up telephone call (2 weeks after treatment completion).
Patients with suboptimal asthma control will be enrolled in the study and
randomly assigned to 1 of 2 parallel groups (Table 4), stratified by
investigational center. The randomization will be done by the IRT system with a
randomization blocks assigned to a study site when the site is ready to
randomize patients. The IRT system manages this process automatically. The BF
Digihaler DS group patients will use the BF Digihaler with the App and DHP
(Cloud solution). The SoC group patients will be treated with their current
treatment prescribed by the investigational center to the patient based on
asthma guidelines and clinician judgement. The SoC group patients will not use
the DS during the treatment period. Similar data will be collected regarding
outcomes for both groups, which are as follows: ACT, Mini AQLQ and WPAI
questionnaire responses, and the frequency of CAEs.
Table 4: Description of Treatment Groups
BF Digihaler DS group Standard of Care
group
BF Digihaler* (as MART) + App Current rescue medication,
ICS/LABA and any additional controller medication for asthma
DHP (Cloud solution) Not applicable
HCP-facing dashboard Not applicable
App=mobile phone application; BF Digihaler=budesonide/formoterol electronic
multidose dry powder inhaler; DHP=Digital Health Platform; DS=Digital System;
HCP=healthcare professional; ICS=inhaled corticosteroid; LABA=long-acting beta2
agonist; MART=maintenance and reliever therapy.
* If needed, the HCP can add another controller medication other than an ICS
with LABA, including a biologic, to the DS and SoC patient*s treatment.
All patients will have a screening/baseline visit, at which they will be asked
if they own a mobile phone (with iOS or Android) and use different applications
on their mobile phone. A baseline ACT score and Mini AQLQ and WPAI
questionnaire responses for all patients will be collected. At Visit 1,
patients in the BF Digihaler DS group will be trained on the use of the BF
Digihaler (including instructions on how to use the inhaler and the App), and
patients in the SoC group will be re trained on the use of their current
inhalers. Upon demonstrating competency, patients in the BF Digihaler DS group
will have their maintenance ICS with LABA and rescue medication or
ICS/formoterol MART switched to the BF Digihaler given as MART (at a dose of BF
comparable to their most recent current ICS dose). All other asthma maintenance
medications, except for ICS with LABA, may be continued. If needed, the HCP can
add another controller medication other than an ICS with LABA, including a
biologic, to the DS and SoC patient*s treatment. Patients in the SoC group will
receive reimbursement for their maintenance ICS with LABA and rescue
medications according to their specific country*s policy.
Investigational centers will receive similar instruction regarding features of
the App, as well as features of the associated dashboard, which mirrors the
digital information obtained from the BF Digihaler and the App, including
frequency and times of inhaler use and associated inspiratory flow parameters
measured by the BF Digihaler with each inhalation (peak inhalation flow and
inhaled volume).
At the baseline visit (Visit 1), the following information from the patient*s
EMR will be collected, if available: blood eosinophils, FeNO, IgE (total), and
lung function (FEV1, FVC, FEV1/FVC).
Patients in both the BF Digihaler DS and the SoC groups will be followed for
their asthma according to the clinical judgement of the investigator; the
asthma of patients in both groups will be managed in a manner consistent with
the clinical judgement of the investigator and based on local practices,
routines, and asthma management guidelines (eg, Global Initiative for Asthma
[GINA]). In addition, the BF Digihaler DS group patients will be followed by
the investigational centers with the addition of objective information on BF
Digihaler usage being available to both patients and investigational centers
through the App and the dashboard, respectively. The HCPs will check the
dashboard at least once a week per patient and use this information, along with
any other additional information about the patient, as per their clinical
judgement, to modify patients* asthma management. The investigator may, if
indicated, modify the patient*s regime, including adding asthma controllers or
biologics as otherwise clinically indicated in the judgement of the
investigator. Clinically Driven Assessments for both groups, if necessary,
should be arranged per the clinical judgement of the HCP managing the patient
and can be via a video call, a telephone call, or an on-site visit.
For all patients, at Visit 2, Visit 3, and any Clinically Driven Assessment,
the HCP will record answers to Asthma Management questions, including
discussions regarding adherence, or inhaler technique, treatment adjustments,
or additions of new treatments, including biologic medication usage.
Additionally, in the case of a Clinically Driven Assessment, the HCP will be
asked whether or not the contact with the patient was originated from the HCP
interaction with the dashboard.
The ACT and Mini AQLQ will be completed on Visit 2.
At the end of the treatment period (24 weeks, Visit 3), final assessments of
the DS and SoC groups will be completed, as specified in the study procedures
and assessments schedule (Table 5), and the rest of the inhalers that were
dispensed to the BF Digihaler DS group patients will be returned to the
investigational center. Two weeks after the return of the inhalers, the
investigational center will perform a follow-up telephone call for all
patients, and will confirm that the BF Digihaler DS group patients have
returned to their previous asthma treatments.
It should also be noted that no specific clinical decisions are being mandated.
One secondary objective of this study is to describe how clinicians actually
use the information provided by the DS to manage their patients.
Intervention
Budesonide/formoterol 160/4.5 mcg powder for oral inhalation
1-2 inhalations, twice daily; 1 additional inhalation as needed in response to
symptoms. Not more than 6 inhalations should be taken on any single occasion. A
total daily dose of more than 8 inhalations is not normally needed; however, a
total daily dose of up to 12 inhalations could be used for a limited period.
Patients using more than 8 inhalations daily should be strongly recommended to
seek medical advice.
Study burden and risks
1.3. Known and Potential Benefits and Risks to Patients
The investigational product, BF Digihaler, delivers a dose of BF equivalent to
DUORESP SPIROMAX and adds electronic capabilities intended to provide patients
with feedback to potentially improve inhalation technique, disease
understanding, management, and outcomes. The addition of the integrated
electronic module has no impact on the pharmaceutical performance of the BF
Digihaler relative to BF SPIROMAX, and it does not affect the user steps
required to take a dose (performance and functional testing on file at Teva).
Additional information regarding benefits and risks of BF Digihaler to patients
may be found in the Investigator*s Brochure (IB).
Van Swietenlaan 6
Groningen 9728NZ
NL
Van Swietenlaan 6
Groningen 9728NZ
NL
Listed location countries
Age
Inclusion criteria
Inclusion Criteria: Patients may be included in the study only if they meet all
of the following criteria:
a. The patient is 18 years or older at the time of screening.
b. The patient has a documented diagnosis of asthma established at the
investigational center at the time of informed consent or the investigator
confirms a diagnosis of asthma.
c. The patient is currently on treatment with a moderate- to high-dose ICS with
LABA.
d. The patient has an ACT score of less than 19 at the screening/baseline visit.
e. The patient is willing to discontinue all other maintenance ICS with LABA
medications and rescue medications and replace them with the study-provided BF
Digihaler as MART for the duration of the trial, if randomized to the BF
Digihaler DS group. All other asthma maintenance medications, except for ICS
with LABA, may be continued.
f. The patient can read fluently and communicate in United Kingdom English,
Dutch, or German, as applicable, and is familiar with and is willing to use
his/her own mobile phone that meets the minimum App requirements and download
and use the App.
g. The patient is able to provide written informed consent.
h. The patient must be willing and able to comply with study requirements and
restrictions and to remain at the investigational center for the required
duration during the study period, and willing to return to the investigational
center for the follow up procedures and assessments as specified in this
protocol.
Exclusion criteria
Exclusion Criteria: Patients will be excluded from participating in this study
if they meet any of the following criteria:
a. The patient has any clinically significant uncontrolled medical condition
(treated or untreated) other than asthma, which in the view of the investigator
would preclude participation.
b. The patient has any medical or psychiatric condition that, in the opinion of
the investigator, could jeopardize or would compromise the patient*s ability to
participate in this study.
c. The patient is currently using or has used, in the 12 months prior to
enrollment, a digital inhaler system designed to monitor inhaler usage such as,
but not limited to, the Propeller Health, Adherium, or Amiko systems.
d. The patient has a diagnosis of chronic obstructive pulmonary disease (COPD)
or asthma-COPD overlap (ACO).
e. The patient is a current smoker or has a greater than 10 pack-year history
of smoking.
f. The patient was treated for asthma exacerbation, including hospitalization
or emergency visits, in the last 30 days.
g. The patient is currently being treated with systemic corticosteroids (oral,
intramuscular, or intravenous) or has been treated within the last 30 days.
h. The patient has any treatment with biologics for asthma (eg, omalizumab,
anti interleukin (IL)5, anti-IL5R, anti-IL4R), or has had such treatment within
the last 90 days.
i. The patient has a known hypersensitivity to any components of the IMPs
stated in this protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-003951-41-NL |
| CCMO | NL82348.100.23 |