None listed
Conditions
Brief summary
In this study, we will address the following specific research question: can a single-dose of tocilizumab prevent allergen-induced airway inflammation and bronchoconstriction? Tocilizumab will be administered intravenously as a single dose of 8mg/kg seven days before allergen challenge. This combination of dose and route of administration is currently approved in Australia to treat patients with rheumatoid arthritis monthly. Lung function will be assessed periodically in the 7h following allergen challenge. Airway inflammation will be measured at 7h and 24h following allergen challenge. Bronchoconstriction and airway inflammation will be compared between the TCZ and placebo groups to determine drug efficacy.
Interventions
This is a double-blind, placebo-controlled trial to evaluate the efficacy of a drug (tocilizumab) that blocks the interleukin-6 receptor for the treatment of allergen-induced asthma. Individuals with stable, mild to moderate allergic asthma, with a history of episodic wheeze and shortness of breath, will be eligible for enrolment. The study is divided into 2 parts.
Part 1: Baseline (visit 1-4)
1. Participants who meet all entry criteria and provide informed consent will then be screened with a
This is a double-blind, placebo-controlled trial to evaluate the efficacy of a drug (tocilizumab) that blocks the interleukin-6 receptor for the treatment of allergen-induced asthma. Individuals with stable, mild to moderate allergic asthma, with a history of episodic wheeze and shortness of breath, will be eligible for enrolment. The study is divided into 2 parts. Part 1: Baseline (visit 1-4) 1. Participants who meet all entry criteria and provide informed consent will then be screened with a history, physical examination, spirometry, and routine laboratory tests. 2. Their atopic status will be documented by skin testing against common airborne allergens. 3. Their rs4129267 Single Nucleotide Polymorphism (SNP) genotype will be determined 4. If they continue to meet entry criteria, an allergen challenge will be performed to confirm the presence of an early and late phase response. 5. Histamine challenge test and sputum differentials will be performed before and after allergen challenges. 6. To enter into Part 2 of the study, participants must have: -Documented early and late asthmatic response to inhaled incremental allergen challenge; - rs4129267 genotype TT or CT; and - Allergic sensitisation to house dust mite Visit 1 : Baseline screening: Obtain informed consent. Subjects screened with a history, physical examination, spirometry and routine laboratory tests. Visits 2 to 4 : Baseline allergen challenge: Perform Histamine challenge, allergen inhalation test and sputum induction to assess eligibility for entry into Part 2 Part 2: Treatment and Follow-up (visit 5-10) 1. Participants will be randomised to receive the drug tocilizumab 8mg/kg or placebo by a single dose intravenous infusion. 2. Spirometry, vital signs, asthma symptomatology, histamine challenge, sputum differentials will be evaluated 6 days after drug/placebo. 3. 24 hours later, an allergen inhalation challenge test is performed, with spirometry measured until 7 hours post-challenge. Sputum will also be induced at 7 hours following the allergen challenge. 4. Histamine challenge and sputum induction will be performed again 24 hours after allergen challenge. 5. Any AEs and asthma symptoms will be evaluated at each clinic visit. 6. A physical examination, spirometry and laboratory tests will performed at the termination visit, 28 days after drug/placebo. Visit 5 : Study drug infusion: Tocilizumab or placebo given as intravenous infusion. Visits 6 to 8 : Post-treatment allergen challenge: Perform Histamine challenge, allergen inhalation test and sputum induction. Visit 9 : Follow-Up Visit: Spirometry, vital signs, asthma symptomatology and laboratory tests. Visit 10 : Termination: Physical examination, spirometry, vital signs and laboratory tests Participants will be compensated to help retention rates and adherence to the protocol's requirements.
Sponsors
QIMR Berghofer Medical Research Institute
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
For Part 1 of the study: 1.Male/female volunteers 18-65 years of age. 2.General good health. 3.Mild to moderate, stable, allergic asthma. 4.History of episodic wheeze and shortness of breath. 5.FEV(1) at baseline at least 70percent of the predicted value. 6.Positive skin-prick test to common allergens. 7.Able to comprehend and follow all required study procedures 8.Willing and able to sign an informed consent form. For Part 2 of the study: 1. Positive histamine challenge test. 2. Positive allergen-induced early and late airway bronchoconstriction. 3. rs4129267 genotype TT or CT
Exclusion criteria
General: 1.History or symptoms of clinically significant autoimmune disease; 2.Lung disease other than mild to moderate allergic asthma; 3.Recent history of alcohol dependency; 4.Use of tobacco products of any kind currently or within the previous 12 months, or smoking history greater than 10 pack years; 5.Unwillingness or inability to comply with the study protocol for any other reason; Previous or concomitant therapy: 6.Use of corticosteroids, immunosuppressives, anticoagulants or any medications that may interact with drug within 28 days prior to treatment randomization; 7.Have chronic use of any other medication for treatment of allergic lung disease other than short- and intermediate-acting Beta2-agonists or ipratropium bromide; 8.Participation in any other investigational drug treatment protocol within the preceding 30 days or 5 half lives of the drug; Exclusions for general safety: 9.A worsening of asthma or a respiratory tract infection within 6 weeks preceding study entry; 10.History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or lightheadedness; 11.History or symptoms of cardiovascular disease; 12.History or symptoms of significant neurologic disease; 13.History of serious adverse reaction or hypersensitivity to any drug; 14.Abnormal chest X-ray; 15.Abnormal electrocardiogram; 16.History of clinically significant hematologic abnormality; 17.History of intestinal ulceration or diverticulitis. 18.Clinically significant abnormalities in laboratory test results; 19.Women not using adequate contraception, actively seeking pregnancy, pregnant or lactating or have positive serum pregnancy test at screening or positive urine pregnancy test during the study; 20.History of, or known currently active, recurrent bacterial, viral, fungal, mycobacterial or other infections. 21.Primary or secondary immunodeficiency. 22.Patients with lack of peripheral venous access. 23.Concomitant disease or condition which could interfere with the conduct of the study or pose an unacceptable risk to the subject. 24.Development of severe asthma reaction during the screening allergen challenge that could not be rescued by bronchodilator alone. Laboratory exclusion criteria (at visits 1 to 4): 25.Serum aspartate transaminase or alanine transaminase greater than 1.5x ULN 26.Absolute neutrophil count less than 2 x 10e9/L 27.Platelet count less than 100 x 10e9/L.
Outcome results
None listed