Tokyo Asthma Study; TOAST

JRCT ID: jRCTs031190237

Registered date:03/03/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Severe asthma
• Date of first enrollment: 16/09/2020
• Target sample size: 100
• Study type: Interventional
• Intervention(s): Questionnaire, peak flow test (morning and evening), airway reversibility test, blood sample collection for special reference (cell function, cytokines, etc.) and sinus CT (if the presence of sinusitis is suspected).

Outcome(s)

• Primary Outcome: Change from the baseline of ACQ-5 at 24 weeks after starting treatment.

Secondary Outcome

Eosinophils, FeNO(Nitrous oxide in exhaled breath) concentrations and IgE are considered as Th2 biomarkers. Amount of changes in ACQ-5 from baseline at 24 weeks of the patient who with high eosinophils alone (>150 microL), with high eosinophils + IgE (over 30IU/mL) or with high eosinophils + FeNO (over 22ppb).
1) One year acute exacerbation at the 56th week.
2) Percentage of patients diagnosed with Good control after intervention with benralizumab at 24 and 56 weeks.
3) Between pre- and post-treatment changes of peripheral blood cytokines and inflammatory mediators.
4) Between pre- and post-treatment changes of immunocompetent cells in peripheral blood.
5) Variation of sputum eosinophils, serum Ig E.
6) Change in airway reversibility.
7) Change in sputum eosinophils before and after treatment.
8) Change in serum IgE (total and antigen specific) before and after treatment.
9) Change in airway reversibility and FEV1 before and after administration of bronchodilators.
10) Peak flow test (morning and evening)
11) The frequency of use of rescue drugs.
12) Change before and after treatment of asthma QOL score.
13) Evaluation of VAS score for asthma using the SACRA questionnaire.
14) Evaluation pre- and post-treatment of HADS score.
15) Nasal symptom questionnaire.
16) Evaluation of Lund-Mackey score on CT pre- and post-treatment (sinus CT is performed only for the patient whose presence of sinusitis is suspected from the nasal condition questionnaire).

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Asthma patients over 20 years old
2) Weight over 40kg
3) Compliance with inhaled steroid (ICS) is over 80% and fluticasone (FP) equivalent ICS has been taken over 1000 micro g/day since 3 months before.
4) In addition to take ICS since 3 months before, at least one long-term administration drug (long -acting beta2 inhalation stimulant (LABA), leukotriene receptor antagonist, inhaled anticholinergic or theophylline) taking.
5) Blood eosinophil count before treatment with benralizumab is over 150 / micro L
6) In addition to the above criteria, the patient must meet at least one of the following criteria.
(1) At least one asthma exacerbation has been diagnosed within two years.
The definition of exacerbation is as follows
(Deterioration requiring treatment with systemic steroids for at least 3 days (when be taken systemic steroids as a long-term medicine, it is defined as temporary increase from maintenance dose), or aggravation requiring emergency outpatient consultation or emergency hospitalization due to asthma)
(2) ACQ-5 score is more than or equal to 1.5 (control failure)
(3) Pre-bronchodilator FEV1 is <80% of predicted value

Exclude criteria

1) Patient who cannot obtain written consent by his/her own free will.
2) Patient complicated with bronchiectasis, diffuse pan bronchiolitis, collagen disease, pulmonary hypertension, sequelae of tuberculosis, interstitial pneumonia, allergic bronchopulmonary aspergilli / mycosis
3) Patient diagnosed with COPD
4) Patient who is smoking or have a history of smoking within 6 months
5) Malignant tumors: patient is in disease or within a year after remission
6) Patient was diagnosed with eosinophilia syndrome, eosinophilic polyangiitis granulomatous disease
7) Patient was diagnosed with parasitic helminth infection within 6 months
8) Patient have already received clinical trials or treatments of benralizumab
9) Patient received bronchial hyperthermia within a year
10) Have a history of anaphylaxis for biological products
11) Patient is being treated with other biologics and the last medication is less than a month
12) Pregnant or nursing woman
13) The condition is not stable because of cardiovascular or gastrointestinal tract, liver, kidney, nerve, musculoskeletal, infection, endocrine, metabolism, blood, mental disorder etc. and serious physical disorder. In addition, a principal investigator or sub-investigators judged that the following items may apply
(1)Affects the safety of the patient while the study period.
(2)Influence the study results and their interpretation
(3)The study will not able to be completed with the condition or situation of the patient
14) Patient diagnosed with acute upper or lower respiratory tract infection requiring administration of antibiotics or antivirals
15) Patient with a history of hypersensitivity for benralizumab and its components.
16) In addition, the attending physician judged the patient as inappropriate

Related Information

• Primary Sponsor: Fukunaga Koichi
• Source(s) of Monetary Support: AstraZeneca K.K.