Clinical Trial Results:
CONNected Electronic Inhalers Asthma Control Trial 3 (“CONNECT 3”), a 24-Week Treatment, Multicenter, Open-Label, Randomized, Parallel Group Comparison Study of Standard of Care Treatment Versus the Budesonide/Formoterol Digihaler Digital System, to Optimize Outcomes in Adult Patients with Asthma
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Summary
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EudraCT number |
2021-003951-41 |
Trial protocol |
NL |
Global end of trial date |
29 Jun 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jun 2024
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First version publication date |
08 Jun 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BFS-AS-40184
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Teva Branded Pharmaceutical Products R&D, Inc.
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Sponsor organisation address |
145 Brandywine Parkway, West Chester, United States, 19380
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Public contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products R&D, Inc., MedInfo@tevaeu.com
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Scientific contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products R&D, Inc., MedInfo@tevaeu.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Aug 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Jun 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Jun 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to demonstrate the effectiveness of the Budesonide/Formoterol (BF) Digihaler Digital System (DS) compared to the Standard of Care (SoC) treatment group.
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Protection of trial subjects |
This clinical study was conducted in accordance with current Good Clinical Practice (GCP) as directed by the provisions of the International Council for Harmonisation (ICH); United States (US) Code of Federal Regulations (CFR), and European Union (EU) Directives and Regulations (as applicable in the region of the study); national country legislation; and the sponsor’s Standard Operating Procedures (SOPs).
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
23 Jan 2023
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
3
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were enrolled and randomized in 2 groups: BF Digihaler DS group and SoC group. A total of 5 participants were randomized; 3 in the SoC group and 2 in the BF Digihaler DS group. One participant from BF Digihaler DS group was excluded from the intent-to-treat (ITT) analysis set due to protected health information (PHI) exposure. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Due to trial cancellation, no participants reached the end of the 24-week treatment period, and no efficacy data were collected or evaluated. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Standard of Care (SoC) | |||||||||||||||||||||
Arm description |
Participants were treated with their current SoC treatment (prescribed by the investigational center to the participant based on asthma guidelines and clinician judgement) and did not use the digital system during the treatment period. SoC treatment included current rescue medication, inhaled corticosteroid (ICS)/ long acting beta2 agonist (LABA) and any additional controller medication for asthma. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
ICS/LABA combinations
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants were treated with their current SoC treatment (prescribed by the investigational center to the participant based on asthma guidelines and clinician judgement).
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Arm title
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Digital System (DS) | |||||||||||||||||||||
Arm description |
Participants were trained on the use of the BF Digihaler (including instructions on how to use the inhaler and the App). Upon demonstrating competency, participants had their maintenance ICS with LABA, and rescue medication or ICS/formoterol maintenance and reliever therapy (MART) switched to the BF Digihaler given as MART (at a dose of BF comparable to their most recent current ICS dose). The BF Digihaler DS consisted of 4 devices: Device 1: BF Digihaler used as MART; Device 2: Patient-facing mobile phone App; Device 3: Digital Health Platform (DHP) (Cloud solution); and Device 4: Healthcare Professional (HCP)-facing dashboard. Participants received budesonide/formoterol 1 to 2 oral inhalations twice daily, based on the equivalent dose of ICS previously used. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Budesonide/Formoterol Digihaler Digital System
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants received budesonide/formoterol 1 to 2 oral inhalations twice daily, based on the equivalent dose of ICS previously used.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: One participant from BF Digihaler DS group was excluded from the ITT analysis set due to PHI exposure. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
All enrolled participants who were randomized to either Standard of Care (SoC) group or Digital System (DS) group. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Standard of Care (SoC)
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Reporting group description |
Participants were treated with their current SoC treatment (prescribed by the investigational center to the participant based on asthma guidelines and clinician judgement) and did not use the digital system during the treatment period. SoC treatment included current rescue medication, inhaled corticosteroid (ICS)/ long acting beta2 agonist (LABA) and any additional controller medication for asthma. | ||
Reporting group title |
Digital System (DS)
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Reporting group description |
Participants were trained on the use of the BF Digihaler (including instructions on how to use the inhaler and the App). Upon demonstrating competency, participants had their maintenance ICS with LABA, and rescue medication or ICS/formoterol maintenance and reliever therapy (MART) switched to the BF Digihaler given as MART (at a dose of BF comparable to their most recent current ICS dose). The BF Digihaler DS consisted of 4 devices: Device 1: BF Digihaler used as MART; Device 2: Patient-facing mobile phone App; Device 3: Digital Health Platform (DHP) (Cloud solution); and Device 4: Healthcare Professional (HCP)-facing dashboard. Participants received budesonide/formoterol 1 to 2 oral inhalations twice daily, based on the equivalent dose of ICS previously used. | ||
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End point title |
Number of Participants Achieving Well-Controlled Asthma or Reaching Clinically Important Improvement in Asthma Control [1] | |||||||||
End point description |
Well-controlled asthma is defined by an asthma control test (ACT) score of greater than or equal to 20. Clinically important improvement in asthma control is defined by an increase of at least 3 ACT units from baseline at the end of the 24-week treatment period. The ACT is a simple, participant-completed tool used for the assessment of overall asthma control. The ACT includes 5 items that assess daytime and nighttime asthma symptoms, use of reliever medication, and impact of asthma on daily functioning. Each item in the ACT is scored on a 5-point scale ranging from 1 (poor control of asthma) to 5 (well control of asthma), with summation of all items providing scores ranging from 5 to 25. The scores span the continuum of poor control of asthma (score of 5) to complete control of asthma (score of 25), with a cutoff score of 19 and below indicating participants with poorly controlled asthma.
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End point type |
Primary
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End point timeframe |
Week 24
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to trial cancellation, no participants reached the end of the 24-week treatment period, and no efficacy data were collected or evaluated. |
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| Notes [2] - Due to trial cancellation, no efficacy data were collected or evaluated. [3] - Due to trial cancellation, no efficacy data were collected or evaluated. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Discussions Between Participant and Investigational Center Healthcare Professional (iHCP) Regarding Inhaler Technique and Regarding Adherence | |||||||||
End point description |
Number of participants who had discussions with iHCP regarding inhaler technique and adherence was to be reported.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 24
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| Notes [4] - Due to trial cancellation, no efficacy data were collected or evaluated. [5] - Due to trial cancellation, no efficacy data were collected or evaluated. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Adjustments of Therapy | |||||||||
End point description |
Number of adjustments of therapy included: Changes to current inhaler therapy (stepping up and stepping down); Change to different inhaled medication; Additional inhaled medication; and Addition of a systemic corticosteroid medication for asthma or another controller, including LAMA or biologics.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 24
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| Notes [6] - Due to trial cancellation, no efficacy data were collected or evaluated. [7] - Due to trial cancellation, no efficacy data were collected or evaluated. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants With Different Frequency of Intervention to Manage Comorbid Conditions Associated With Poor Asthma Control | |||||||||
End point description |
Number of participants with different frequency of intervention to manage comorbid conditions associated (such as gastroesophageal reflux disease, sinusitis, etc.) with poor asthma control was to be reported.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 24
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| Notes [8] - Due to trial cancellation, no efficacy data were collected or evaluated. [9] - Due to trial cancellation, no efficacy data were collected or evaluated. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change From Baseline in Adherence to the BF Digihaler DS When Prescribed as Maintenance Treatment at Week 24 [10] | ||||||||
End point description |
Adherence to maintenance treatment was defined as the percentage of actual inhalation doses taken out of the total number of inhalation doses prescribed over the 24-week treatment period.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is reporting statistics for 'Digital System (DS)' arm only. |
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| Notes [11] - Due to trial cancellation, no efficacy data were collected or evaluated. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in the Work Productivity and Activity Impairment (WPAI) Questionnaire Score at Week 24 | ||||||||||||
End point description |
The WPAI questionnaire is used to measure work productivity and activity impairment. Four metrics are included: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (WI) (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). Total score and each score ranges from 0 (not affected/no impairment) to 100 (completely affected/impaired). Higher scores indicate greater impairment and less productivity.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| Notes [12] - Due to trial cancellation, no efficacy data were collected or evaluated. [13] - Due to trial cancellation, no efficacy data were collected or evaluated. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
System Usability Scale (SUS) Score at Week 24 for the BF Digihaler DS Group [14] | ||||||||
End point description |
The SUS is used to explore device acceptability and usability for participants in the BF Digihaler DS group. It covers a variety of aspects of system usability, such as the need for support, training, and complexity, and thus giving a global view of subjective assessments of usability. It is a 10-question tool (with five response options; from 1=strongly disagree to 5=strongly agree) that provides a composite measure, ranging from 0 to 100, of the overall usability of the system being studied. Higher scores represent a better usability level for the tool.
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End point type |
Secondary
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End point timeframe |
Week 24
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| Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint is reporting statistics for 'Digital System (DS)' arm only. |
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| Notes [15] - Due to trial cancellation, no efficacy data were collected or evaluated. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Adverse events (AEs) or Adverse Device Effects Related to BF Digihaler DS | |||||||||||||||
End point description |
An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Serious adverse events (SAEs) included death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. Number of participants with any AEs, and device-related AEs has been reported. The intent-to-treat (ITT) analysis set included all randomized participants.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug until 2 weeks after end of treatment/early termination (up to Day 152)
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| No statistical analyses for this end point | ||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug until 2 weeks after end of treatment/early termination (up to Day 152)
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Adverse event reporting additional description |
The ITT analysis set included all randomized participants.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
Digital System (DS)
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Reporting group description |
Participants were trained on the use of the BF Digihaler (including instructions on how to use the inhaler and the App). Upon demonstrating competency, participants had 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). The BF Digihaler DS consisted of 4 devices: Device 1: BF Digihaler used as MART; Device 2: Patient-facing mobile phone App; Device 3: DHP (Cloud solution); and Device 4: HCP-facing dashboard. Participants received budesonide/formoterol 1 to 2 oral inhalations twice daily, based on the equivalent dose of ICS previously used. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard of Care (SoC)
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Reporting group description |
Participants were treated with their current SoC treatment (prescribed by the investigational center to the participant based on asthma guidelines and clinician judgement) and did not use the digital system during the treatment period. SoC treatment included current rescue medication, ICS/LABA and any additional controller medication for asthma. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Mar 2022 |
The primary reason for this amendment was to clarify the secondary objective - measuring device defects relating to the Digital System (software/dashboard/app), which was required by the Medicines and Healthcare products Regulatory Agency (MHRA). The device of BF Digihaler in the secondary objective, as well as throughout the protocol where applicable, was stated precise as BF Digihaler Digital System (BF Digihaler DS).
In addition, conducting the semi-structured participant experience interviews was not feasible for this study and therefore was removed from the protocol. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was terminated early due to Teva’s business considerations. The decision to terminate the study was not related to any safety issues or concerns. | |||
