UMIN-CTR Clinical Trial

Public title

Exploration of Novel Biomarkers Associated with Treatment Response to Biologics in Severe Asthma

Acronym

BREAK

Scientific Title

Exploration of Novel Biomarkers Associated with Treatment Response to Biologics in Severe Asthma

Scientific Title:Acronym

BREAK

Region

Japan

Condition

Severe asthma, refractory asthma

Classification by specialty

Pneumology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

This prospective, single-center observational study enrolls patients with severe asthma treated with biologic agents. Biological samples (sputum, blood, nasal brushing, stool) are collected for multi-omics analysis and for analysis of lymphocytes, eosinophils, and epithelial cells; treatment response to biologics is assessed using asthma symptom and QOL questionnaires and lung-function testing. Integrating these data, the aim is to identify novel biomarkers correlated with the efficacy of biologics in severe asthma. The principal measure of treatment effect is the change in ACQ-6 from baseline at 24 weeks. As secondary/exploratory analyses, the proportion achieving clinical remission at 24 weeks (a composite of no maintenance OCS, no exacerbation requiring systemic corticosteroids, ACQ-6 <= 0.75, and lung-function optimization) and its predictors are also evaluated.

Basic objectives2

Others

Basic objectives -Others

Exploratory identification of novel biomarkers correlated with treatment response to biologic therapy (identification of predictors of treatment effect).

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Change from baseline in ACQ-6 (Asthma Control Questionnaire-6) at 24 weeks after initiation of biologic therapy. The minimal clinically important difference (MCID) is defined as 0.5.

Key secondary outcomes

1. Change from baseline in ACQ-6 at 56 weeks.
2. Change from baseline in exacerbation frequency at 24 and 56 weeks.
3. Change from baseline in %FEV1 at 24 and 56 weeks.
4. Change from baseline in FeNO at 24 and 56 weeks.
5. Change from baseline in the SACRA questionnaire and RQLQ (nasal symptoms), AQLQ, and HADS at 24 and 56 weeks.
6. Global Evaluation of Treatment Effectiveness (GETE) at 24 and 56 weeks.
7. Change from baseline in sinus CT Lund-Mackay score at 24 and 56 weeks.
8. Change from baseline in blood eosinophil count and serum total IgE at 24 and 56 weeks.
9. (Exploratory) Functional analysis and RNA sequencing (including single-cell RNA-seq) of peripheral blood PBMCs (lymphocytes, eosinophils) and induced-sputum cells, comprehensive serum cytokine/mediator profiling, gene-expression analysis of nasal-brushing epithelial cells, and stool microbiome and metabolome analysis, at weeks 0, 24, and 56.
10. (Secondary/exploratory) Proportion achieving clinical remission at 24 weeks (four-domain composite: no maintenance oral corticosteroid use, no exacerbation requiring systemic corticosteroids, ACQ-6 <= 0.75, and %FEV1 >= 80% or FEV1 decline from baseline < 5%) and its predictors, including sensitivity analyses under alternative definitions (3-domain, ACQ-6 < 1.5, ACQ-5 substitution, full analysis set treating dropouts as non-remission).

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Severe asthma judged by the attending physician to have poor asthma control despite non-biologic asthma therapy (inhaled corticosteroids [ICS] and other long-term controllers), or despite biologic plus asthma therapy, and likely to improve with initiation or switching of a biologic.
2. Medication adherence >= 80%, and persistence of exacerbations, residual symptoms, or lung-function decline despite >= 3 months of ICS >= 500 microg/day fluticasone-propionate equivalent plus at least one long-term controller (LABA, leukotriene receptor antagonist, inhaled anticholinergic, or theophylline).
3. Aged 20 years or older at the time of consent.
4. Written informed consent obtained.

Key exclusion criteria

1. Contraindication to biologic therapy (history of hypersensitivity to a biologic agent).
(Note: for patients switching from another biologic, an interval of at least 4 weeks between the previous and the new biologic is required.)

Target sample size

200

Name of lead principal investigator

1st name	Jun
Middle name
Last name	Miyata

Organization

Keio University School of Medicine

Division name

Division of Pulmonary Medicine, Department of Medicine

Zip code

160-8582

Address

35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

TEL

03-5363-3794

Email

junmiyata.a2@keio.jp

Name of contact person

1st name	Jun
Middle name
Last name	Miyata

Organization

Keio University School of Medicine

Division name

Division of Pulmonary Medicine, Department of Medicine

Zip code

160-8582

Address

35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

TEL

03-5363-3794

Homepage URL

Email

junmiyata.a2@keio.jp

Institute

Keio University School

Institute

Department

Personal name

Organization

Keio University School

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Keio University School of Medicine Ethics Committee

Address

35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

Tel

03-5363-3503

Email

med-rinri-jimu@adst.keio.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

慶應義塾大学病院（東京都）

Date of disclosure of the study information

2026

Year

09

Month

20

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2022

Year

02

Month

09

Day

Date of IRB

2022

Year

05

Month

09

Day

Anticipated trial start date

2022

Year

09

Month

01

Day

Last follow-up date

2030

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

No treatment intervention (observation only). Patients receive a biologic agent (omalizumab, mepolizumab, benralizumab, dupilumab, tezepelumab, or depemokimab) selected by the attending physician as routine clinical care. With the initiation day defined as week 0, clinical data are collected prospectively at weeks 0, 24, and 56: symptoms (ACQ-6, etc.), exacerbations, oral corticosteroid use, lung function, FeNO, questionnaires, sinus CT, and blood tests. Research biological samples (blood, induced sputum, nasal brushing, stool) are also collected for cellular functional analysis and multi-omics analysis (RNA sequencing, comprehensive cytokine profiling, microbiome and metabolome analysis). Drug choice and dosing follow routine care; no study-specific therapeutic intervention is performed.

Registered date

2026

Year

09

Month

19

Day

Last modified on

2026

Year

09

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071910