Asthma Clinical Trial
Official title:
A Two-arm, Placebo-controlled, Randomized Clinical Trial to Evaluate the Effect of Tezepelumab on Airway Structure and Function in Patients With Uncontrolled Moderate-to-severe Asthma
In adult patients with uncontrolled moderate-to-severe asthma, blocking TSLP with tezepelumab will improve ventilation heterogeneity (evaluated by hyperpolarized 129Xe MRI), and this will be associated with reduced airway inflammation (evaluated by sputum composition), luminal narrowing and plugging (evaluated by CT).
Status | Recruiting |
Enrollment | 30 |
Est. completion date | December 2024 |
Est. primary completion date | September 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - General - Able and willing to provide written informed consent. - Able and willing to comply with the study protocol. - Males and females = 18 years of age. - Asthma-related - Asthma diagnosed by a respiratory physician =12 months prior to study enrolment based on the Global Initiative for Asthma (GINA) 2021 guidelines. - ACQ =1.5 at screening. - Methacholine PC20 = 4 mg/mL OR =15% decrease in FEV1 during saline inhalation for sputum induction OR =15% improvement in FEV1 after bronchodilator during the screening period. - Criteria met for moderate or severe asthma defined by GINA 2021 guidelines, i.e. treatment with low, medium or high dose ICS (<250 mcg, 251 - 500 mcg, >500 mcg of fluticasone equivalent/day respectively) plus another controller. Patients on prednisone would not be excluded, as long as they meet the rest of the inclusion criteria. - FeNO >25 ppb OR =3% sputum eosinophils (preferred) OR blood eos =300/µL during the screening period. - History of =1 exacerbation in the previous year. Exclusion Criteria: - General -- Participation in any clinical trial of an investigational agent or procedure within six months prior to screening or during the study. - Medical conditions and treatment history - History of anaphylaxis to any previous biologic therapy received. - Receipt of live attenuated vaccine within 30 days, receipt of COVID vaccine within 28 days, known or suspected COVID infection at the time of enrollment. - Acute or chronic parasitic, bacterial, fungal or viral infections that required, or currently requires, hospitalization or antimicrobial treatment during the last four weeks. - Acute asthma exacerbation event treated with increased doses of oral, or any dose of intramuscular (IM) or intravenous (IV) corticosteroids within six weeks prior to screening. - Other relevant pulmonary diseases (e.g. chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension, tuberculosis) requiring treatment within 12 months prior to screening. - Alcohol or substance abuse within 12 months prior to screening. - Current smoker defined as having smoked at least one cigarette (or pipe, cigar, or marijuana) per day for = 30 days within the three months prior to screening. - Ex-smokers with = 10 pack-year smoking history. - Pregnancy. - Treatment with anti-IgE, anti-IL-4, anti-IL-5, or anti-IL-13 targeted therapy currently or within three months prior to screening. - MRI-related - Patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist). - In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia. |
Country | Name | City | State |
---|---|---|---|
Canada | Firestone Institute for Respiratory Health | Hamilton | Ontario |
Lead Sponsor | Collaborator |
---|---|
McMaster University |
Canada,
Dunican EM, Elicker BM, Gierada DS, Nagle SK, Schiebler ML, Newell JD, Raymond WW, Lachowicz-Scroggins ME, Di Maio S, Hoffman EA, Castro M, Fain SB, Jarjour NN, Israel E, Levy BD, Erzurum SC, Wenzel SE, Meyers DA, Bleecker ER, Phillips BR, Mauger DT, Gordon ED, Woodruff PG, Peters MC, Fahy JV; National Heart Lung and Blood Institute (NHLBI) Severe Asthma Research Program (SARP). Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018 Mar 1;128(3):997-1009. doi: 10.1172/JCI95693. Epub 2018 Feb 5. — View Citation
Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020 Aug;24(8):777-792. doi: 10.1080/14728222.2020.1783242. Epub 2020 Jun 27. — View Citation
Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, Brightling CE, Griffiths JM, Hellqvist A, Bowen K, Kaur P, Almqvist G, Ponnarambil S, Colice G. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021 May 13;384(19):1800-1809. doi: 10.1056/NEJMoa2034975. — View Citation
Svenningsen S, Haider E, Boylan C, Mukherjee M, Eddy RL, Capaldi DPI, Parraga G, Nair P. CT and Functional MRI to Evaluate Airway Mucus in Severe Asthma. Chest. 2019 Jun;155(6):1178-1189. doi: 10.1016/j.chest.2019.02.403. Epub 2019 Mar 23. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Change in ACQ-5 score. | Change in ACQ-5 score | From baseline (week 0) to endpoint (week 16) | |
Other | Change in AQLQ score. | Change in AQLQ score | From baseline (week 0) to endpoint (week 16) | |
Other | Change in the pre-bronchodilator and post-bronchodilator FEV1. | Change in the pre-bronchodilator and post-bronchodilator FEV1 measured in litres | From baseline (week 0) to endpoint (week 16) | |
Other | Change in the post-bronchodilator reversibility of FEV1. | Change in the post-bronchodilator reversibility of FEV1 measured in litres | From baseline (week 0) to endpoint (week 16) | |
Other | Change in airways resistance and reactance measured by airwave oscillometry (R5, R20, R5-R20, X5, Ax). | Change in airways resistance and reactance measured by airwave oscillometry (R5, R20, R5-R20, X5, Ax) | From baseline (week 0) to endpoint (week 16) | |
Other | Change in FeNO. | Change in FeNO measured as parts per billion | From baseline (week 0) to endpoint (week 16) | |
Other | Change in blood eosinophil counts. | Change in blood eosinophil measured as cells per litre | From baseline (week 0) to endpoint (week 16) | |
Other | Change in blood neutrophil counts. | Change in blood neutrophil counts measured as cells per litre | From baseline (week 0) to endpoint (week 16) | |
Other | Change in sputum eosinophil counts. | Change in sputum eosinophil counts measured as % total nucleated cells. | From baseline (week 0) to endpoint (week 16) | |
Other | Change in sputum neutrophil counts. | Change in sputum neutrophil counts measured as % total nucleated cells. | From baseline (week 0) to endpoint (week 16) | |
Other | Change in eosinophil extracellular traps (including surrogate biomarkers histones, double stranded DNA and formalin fixed paraffin embedded sputum plugs). | Change in absorbance values by fluorescence | From baseline (week 0) to endpoint (week 16) | |
Other | Change in galectin-10 levels | Change in galectin-10 concentration in sputum supernatant. | From baseline (week 0) to endpoint (week 16) | |
Other | Change in sputum T2 cytokines. | Change in sputum T2 cytokines. | From baseline (week 0) to endpoint (week 16) | |
Other | Change in markers of airway eosinophil activity | Change in eosinophil peroxidase (EPX) levels (ng/uL) | From baseline (week 0) to endpoint (week 16) | |
Other | Change in markers of airway eosinophil activity | Change in free eosinophil granules (FEGs) (none, few, moderate, many) | From baseline (week 0) to endpoint (week 16) | |
Primary | Change in pre-bronchodilator 129Xe MRI ventilation defect percent (VDP). | Change from baseline to week 16 in the pre-bronchodilator 129Xe MRI ventilation defect percent (VDP). | 16 weeks from randomization (week 0) to endpoint assessment (week 16) | |
Secondary | Change in the post-bronchodilator 129Xe MRI ventilation defect percent (VDP). | Change in the post-bronchodilator 129Xe MRI ventilation defect percent (VDP) measured as percent of total ventilation. | From baseline (week 0) to endpoint (week 16) | |
Secondary | Change in the CT mucus score (i.e. intraluminal plugging). | Change in the CT mucus score (i.e. intraluminal plugging) measured using a mucus score. | From baseline (week 0) to endpoint (week 16) | |
Secondary | Change in the CT airway lumen area. | Change in the CT airway lumen area measured in mm^2. | From baseline (week 0) to endpoint (week 16) | |
Secondary | Change in the CT airway wall area. | Change in the CT airway wall area measured in mm^2. | From baseline (week 0) to endpoint (week 16) | |
Secondary | Change in the CT airway wall area percentage. | Change in the CT airway wall area percentage measured as a percentage of total airway area (wall area + airway lumen). | From baseline (week 0) to endpoint (week 16) | |
Secondary | Change in the CT total airway count. | Change in the CT total airway count | From baseline (week 0) to endpoint (week 16) | |
Secondary | Change in the CT gas trapping. | Change in the CT gas trapping | From baseline (week 0) to endpoint (week 16) | |
Secondary | Change in the post-bronchodilator reversibility of 129Xe MRI VDP. | Change in the post-bronchodilator reversibility of 129Xe MRI VDP measured by ventilation defect percentage of total ventilation | From baseline (week 0) to endpoint (week 16) |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT04410523 -
Study of Efficacy and Safety of CSJ117 in Patients With Severe Uncontrolled Asthma
|
Phase 2 | |
Completed |
NCT04624425 -
Additional Effects of Segmental Breathing In Asthma
|
N/A | |
Active, not recruiting |
NCT03927820 -
A Pharmacist-Led Intervention to Increase Inhaler Access and Reduce Hospital Readmissions (PILLAR)
|
N/A | |
Completed |
NCT04617015 -
Defining and Treating Depression-related Asthma
|
Early Phase 1 | |
Recruiting |
NCT03694158 -
Investigating Dupilumab's Effect in Asthma by Genotype
|
Phase 4 | |
Terminated |
NCT04946318 -
Study of Safety of CSJ117 in Participants With Moderate to Severe Uncontrolled Asthma
|
Phase 2 | |
Completed |
NCT04450108 -
Vivatmo Pro™ for Fractional Exhaled Nitric Oxide (FeNO) Monitoring in U.S. Asthmatic Patients
|
N/A | |
Completed |
NCT03086460 -
A Dose Ranging Study With CHF 1531 in Subjects With Asthma (FLASH)
|
Phase 2 | |
Completed |
NCT01160224 -
Oral GW766944 (Oral CCR3 Antagonist)
|
Phase 2 | |
Completed |
NCT03186209 -
Efficacy and Safety Study of Benralizumab in Patients With Uncontrolled Asthma on Medium to High Dose Inhaled Corticosteroid Plus LABA (MIRACLE)
|
Phase 3 | |
Completed |
NCT02502734 -
Effect of Inhaled Fluticasone Furoate on Short-term Growth in Paediatric Subjects With Asthma
|
Phase 3 | |
Completed |
NCT01715844 -
L-Citrulline Supplementation Pilot Study for Overweight Late Onset Asthmatics
|
Phase 1 | |
Terminated |
NCT04993443 -
First-In-Human Study to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of LQ036
|
Phase 1 | |
Completed |
NCT02787863 -
Clinical and Immunological Efficiency of Bacterial Vaccines at Adult Patients With Bronchopulmonary Pathology
|
Phase 4 | |
Recruiting |
NCT06033833 -
Long-term Safety and Efficacy Evaluation of Subcutaneous Amlitelimab in Adult Participants With Moderate-to-severe Asthma Who Completed Treatment Period of Previous Amlitelimab Asthma Clinical Study
|
Phase 2 | |
Completed |
NCT03257995 -
Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Two Orally Inhaled Indacaterol Salts in Adult Subjects With Asthma.
|
Phase 2 | |
Completed |
NCT02212483 -
Clinical Effectiveness and Economical Impact of Medical Indoor Environment Counselors Visiting Homes of Asthma Patients
|
N/A | |
Recruiting |
NCT04872309 -
MUlti-nuclear MR Imaging Investigation of Respiratory Disease-associated CHanges in Lung Physiology
|
||
Withdrawn |
NCT01468805 -
Childhood Asthma Reduction Study
|
N/A | |
Recruiting |
NCT05145894 -
Differentiation of Asthma/COPD Exacerbation and Stable State Using Automated Lung Sound Analysis With LungPass Device
|