UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000040859
Receipt number R000046621
Scientific Title Activation status of eosinophils in severe asthma patients treated with biologics
Date of disclosure of the study information 2020/07/01
Last modified on 2023/12/08 18:14:38

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Basic information

Public title

Activation status of eosinophils in severe asthma patients treated with biologics

Acronym

ACT study

Scientific Title

Activation status of eosinophils in severe asthma patients treated with biologics

Scientific Title:Acronym

ACT study

Region

Japan


Condition

Condition

Severe asthma
Mild asthma

Classification by specialty

Pneumology Clinical immunology

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To elucidate the variable activation status of circulating eosinophils in severe asthma and mild asthma by performing RNA-seq in whole blood cells and purified blood eosinophils. Then, to evaluate the phenotypic alterations of blood eosinophils after treatment with the biologics mepolizumab, omalizumab, or dupilumab in the same way.

Basic objectives2

Efficacy

Basic objectives -Others


Trial characteristics_1


Trial characteristics_2


Developmental phase



Assessment

Primary outcomes

Elucidation of the phenotypic heterogeneity of circulating eosinophils in severe asthma and mild asthma by performing RNA-seq in whole blood cells and purified blood eosinophils.

Key secondary outcomes

Subsequent evaluation of the phenotypic alterations of blood eosinophils after treatment with the biologics mepolizumab, omalizumab, and dupilumab.


Base

Study type

Observational


Study design

Basic design


Randomization


Randomization unit


Blinding


Control


Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

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



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit


Not applicable

Gender

Male and Female

Key inclusion criteria

Inclusion criteria for all participants
1. All participants are over 20 years old and are required to have received a clinical diagnosis of eosinophilic asthma by a physician.
2. Informed consents from all participants are obtained.

Specific inclusion criteria for each group
Participant group 1 (N=5).
1. Mild eosinophilic asthma who have an elevated peripheral blood eosinophil count of 150 cells per uL or more at Visit 1

Participant group 2 (N=5 for each treatment, total N=15)
1. Severe eosinophilic asthma patients already being on the treatment of any biologic (mepolizumab, omalizumab, or dupilumab). These patients must be taking a biologic for at least 4 months with a good clinical response using GETE score.

2. These patients must have had at least one asthma exacerbation in the previous year before starting biologics, that required treatments with systemic glucocorticoids or some biologics while they were receiving treatment with high dose inhaled corticosteroid (ICS) with additional controllers.

Participant group 3 (N=3 for each biologic, total N=9),
1. Severe asthma patients who are going to take mepolizumab, omalizumab, or dupilumab for the first time.
2. These patients have an elevated peripheral blood eosinophil count of 150 cells per uL or more at Visit 1.
3. These patients must have had at least one asthma exacerbation in the previous year that required treatments with systemic glucocorticoids or some biologics while they were receiving treatment with high dose inhaled corticosteroid (ICS) with additional controllers.
4. In the cases of severe asthma patients who have already been treated with some biologics, these patients never had a good asthma control with the currently used biologic.
5. Based on the clinical practice, the participation in this study should be considered after a new biologic was determined based on agreement between the attending physician and the patient. Only if consent can be obtained thereafter.

Key exclusion criteria

Exclusion criteria for all participant group
1. Concurrent Respiratory Disease: Presence of a known pre-existing, clinically important lung condition other than asthma.
2. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening.
3. Liver Disease: Known, pre-existing, unstable liver disease.
4. Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
5. Other Concurrent Medical Conditions: Subjects who have known, pre-existing,
clinically significant endocrine, autoimmune, metabolic, neurological, renal,
gastrointestinal, hepatic, haematological or any other system abnormalities that
are uncontrolled with standard treatment.
6. Eosinophilic Diseases: Subjects with other conditions that could lead to elevated
eosinophils such as hyper-eosinophilic syndrome, Churg-Strauss syndrome, or eosinophilic esophagitis.
7. Pregnancy: Subjects who are pregnant or breastfeeding.

Specific exclusion criteria for each group
Participant group 3 (N = 3 for each biologic, total N=9),
1. Participants who have received any biologics (mepolizumab, omalizumab, benralizumab, or dupilumab) within 56 days before Visit 1.

Target sample size

29


Research contact person

Name of lead principal investigator

1st name Masashi
Middle name
Last name Matsuyama

Organization

University of Tsukuba Hospital

Division name

Department of respiratory medicine

Zip code

305-8575

Address

1-1-1, Tennoudai, Tsukuba, Ibaraki, Japan

TEL

029-853-3144

Email

mmatsuyama@md.tsukuba.ac.jp


Public contact

Name of contact person

1st name Masashi
Middle name
Last name Matsuyama

Organization

University of Tsukuba Hospital

Division name

Department of respiratory medicine

Zip code

305-8575

Address

1-1-1, Tennoudai, Tsukuba, Ibaraki, Japan

TEL

029-853-3144

Homepage URL


Email

mmatsuyama@md.tsukuba.ac.jp


Sponsor or person

Institute

Department of respiratory medicine, University of Tsukuba Hospital

Institute

Department

Personal name



Funding Source

Organization

GlaxoSmithKline, Inc. (GSK)

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

UK


Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Tsukuba Clinical Research & Development Organization

Address

2-1-1, Amakubo, Tsukuba, Ibaraki, Japan, 305-8576

Tel

029-853-3914

Email

t-credo.adm@un.tsukuba.ac.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions



Other administrative information

Date of disclosure of the study information

2020 Year 07 Month 01 Day


Related information

URL releasing protocol


Publication of results

Unpublished


Result

URL related to results and publications


Number of participants that the trial has enrolled

27

Results

We evaluated the variation in gene expression profiles of peripheral blood eosinophils before and after starting treatment with mepolizumab. The expression of genes associated with IL-5/IL-5R signaling was decreased in eosinophils of patients treated with mepolizumab compared to that before starting mepolizumab. In contrast, genes particularly associated with type 1 eosinophils were upregulated after treatment with mepolizumab.

Results date posted

2023 Year 12 Month 08 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

Twenty-seven cases were actually enrolled.

Group 1 (mild asthma): 6 cases
Group 2 (severe asthma on treatment with biologics): 13 cases
Group 3 (severe asthma before treatment with new biologics): 8 cases

Following the protocol, the following number of cases were included in the analysis after excluding cases with eosinophil counts less than 150 in the actual sample.

Group 1 (mild asthma): 5 cases
Group 2 (severe asthma on treatment with biologic): 12 cases
Group 3 (severe asthma before treatment with new biologics): 7 cases

Participant flow


Adverse events

Nothing

Outcome measures


Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2020 Year 04 Month 02 Day

Date of IRB

2020 Year 04 Month 02 Day

Anticipated trial start date

2020 Year 10 Month 01 Day

Last follow-up date

2023 Year 02 Month 28 Day

Date of closure to data entry

2023 Year 02 Month 28 Day

Date trial data considered complete

2024 Year 05 Month 31 Day

Date analysis concluded

2024 Year 05 Month 31 Day


Other

Other related information

To elucidate the variable activation status of circulating eosinophils in severe asthma and mild asthma by performing RNA-seq in whole blood cells and purified blood eosinophils. Then, to evaluate the phenotypic alterations of blood eosinophils after treatment with the biologics mepolizumab, omalizumab, or dupilumab in the same way.


Management information

Registered date

2020 Year 06 Month 22 Day

Last modified on

2023 Year 12 Month 08 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046621


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name