Clinical Trials Register

Summary
EudraCT Number:	2021-003951-41
Sponsor's Protocol Code Number:	BFS-AS-40184
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-12-01
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2021-003951-41

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Study to Test if Using the BF Digihaler System is Effective in Getting Better Control of Asthma in Adult Patients Compared to Usual Care

A.4.1

Sponsor's protocol code number

BFS-AS-40184

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Teva Branded Pharmaceutical Products R&D, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Teva Branded Pharmaceutical
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Teva Branded Pharmaceutical Products R&D, Inc.
B.5.2	Functional name of contact point	Guilherme Safioti
B.5.3	Address:
B.5.3.1	Street Address	145 Brandywine Parkway
B.5.3.2	Town/ city	West Chester
B.5.3.3	Post code	19380
B.5.3.4	Country	United States
B.5.4	Telephone number	+46702997636
B.5.6	E-mail	Guilherme.safioti@tevapharm.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Budesonide/Formoterol Digihaler Digital System
D.3.4	Pharmaceutical form	Inhalation powder
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Formoterol Fumarate Dihydrate
D.3.9.1	CAS number	183814-30-4
D.3.9.4	EV Substance Code	SUB25660
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Budesonide
D.3.9.1	CAS number	51333-22-3
D.3.9.4	EV Substance Code	SUB05955MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	160
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ICS/LABA combinations
D.2.1.1.2	Name of the Marketing Authorisation holder	NA
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	ICS/LABA combinations
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Asthma

E.1.1.1

Medical condition in easily understood language

Asthma

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to demonstrate the effectiveness of the digital system compared to the Standard of Care group

E.2.2

Secondary objectives of the trial

The secondary objective (#1) is to describe the asthma management actions by Health Care Professionals for all patients in both groups.
The secondary objective (#2) is to evaluate adherence patterns to maintenance treatment (BF Digihaler) in the Digital System (DS) group.
The secondary objective (#3) is to evaluate work productivity and activity impairment in asthma patients in both groups.
The secondary objective (#4) is to assess the usability and acceptability of the Digital System by patients in the DS group and the investigational center personnel.
The secondary objective (#5) is to evaluate the safety of BF Digihaler DS.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion 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.

E.4

Principal exclusion 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.

E.5 End points

E.5.1

Primary end point(s)

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline at the end of the 24-week treatment period

E.5.2

Secondary end point(s)

Secondary endpoint #1 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 for 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 a long-acting muscarinic antagonist (LAMA) or biologics
 frequency of intervention to manage comorbid conditions associated with poor asthma control (gastroesophageal reflux disease, sinusitis, etc.)
Secondary endpoint #2 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.
Secondary endpoint #3 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.
Secondary endpoint #4 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.
Secondary endpoint #5 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

E.5.2.1

Timepoint(s) of evaluation of this end point

24 weeks

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Netherlands

Germany

Ireland

United Kingdom

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

End of study is defined as the follow-up telephone call for the last patient

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

250

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

250

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2022-12-01.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

400

F.4.2.2

In the whole clinical trial

500

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

No treatment is planned by the sponsor after the end of the study. Patients are advised to consult with their primary physician for treatment

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-12-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-05-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-06-29

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