Tezepelumab for Severe Asthma in Children (HORIZON Trial)
Palo Alto (17 mi)Age: < 18
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?To assess the efficacy and safety of tezepelumab in pediatric participants with severe uncontrolled asthma on medium to high-dose inhaled corticosteroids (ICS) and at least one additional asthma controller medication with or without oral corticosteroids.
What data supports the idea that Tezepelumab for Severe Asthma in Children is an effective drug?The available research shows that Tezepelumab is effective in treating severe asthma. It significantly reduces the number of asthma attacks and improves lung function. In studies, patients using Tezepelumab had fewer asthma attacks compared to those who received a placebo. Additionally, the drug improved breathing capacity and did not cause more side effects than the placebo. These results suggest that Tezepelumab is a beneficial option for managing severe asthma.267811
What safety data exists for Tezepelumab in treating severe asthma in children?The provided research does not contain safety data for Tezepelumab or its other names (Tezspire, tezepelumab-ekko, AMG 157, MEDI-9929). The studies focus on the safety and efficacy of Tocilizumab and Secukinumab for juvenile idiopathic arthritis, not Tezepelumab for asthma.134913
Is the drug Tezepelumab a promising treatment for severe asthma in children?Yes, Tezepelumab is a promising treatment for severe asthma. It has been approved by the FDA for people 12 and older with severe asthma not controlled by other medications. It works by targeting a specific protein involved in asthma inflammation, helping to reduce asthma attacks and improve breathing.2571012
Do I have to stop taking my current medications for the trial?The trial does not specify if you need to stop your current medications. However, it requires that you continue taking medium to high-dose inhaled corticosteroids and at least one additional asthma controller medication. Please consult with the trial coordinators for more details.
Eligibility Criteria
This trial is for children aged 5 to less than 12 with severe asthma, who are already on medium to high-dose inhaled corticosteroids and another asthma controller. They must have had at least two serious flare-ups or one hospitalizing event in the past year, weigh over 16 kg, and show certain levels of lung function.Inclusion Criteria
I am between 5 and 11 years old.
I've had at least 2 severe asthma attacks or 1 that led to hospitalization in the last year.
My weight is at least 16 kg during my first and third visits.
My asthma diagnosis is confirmed by specific breathing tests.
My asthma is not under control.
Exclusion Criteria
I have a history of cystic fibrosis, primary ciliary dyskinesia, or chronic sinusitis with nasal polyps.
I've had a severe asthma attack that led to a seizure or needed a breathing machine.
Treatment Details
The study tests Tezepelumab's effectiveness and safety against a placebo in managing severe asthma in kids. Participants will be randomly assigned to receive either Tezepelumab or a placebo alongside their standard asthma treatments.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: TezepelumabExperimental Treatment1 Intervention
Participants will be receiving tezepelumab subcutaneous injection
Group II: PlaceboPlacebo Group1 Intervention
Participants will be receiving placebo through a subcutaneous injection
Tezepelumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tezspire for:
- Severe asthma
🇪🇺 Approved in European Union as Tezspire for:
- Severe asthma
Find a clinic near you
Research locations nearbySelect from list below to view details:
Research SiteCoppell, TX
Research SiteEdmonton, Canada
Research SiteLa Jolla, CA
Research SiteBoston, MA
More Trial Locations
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Who is running the clinical trial?
AstraZenecaLead Sponsor
AmgenIndustry Sponsor
References
Safety and response to influenza vaccine in patients with systemic-onset juvenile idiopathic arthritis receiving tocilizumab. [2022]We investigated the safety and efficacy of administering influenza vaccines to patients with systemic-onset juvenile idiopathic arthritis (sJIA) treated with tocilizumab.
Tezepelumab in Adults with Uncontrolled Asthma. [2022]In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.
Patient satisfaction and clinical effectiveness of switching from intravenous tocilizumab to subcutaneous tocilizumab in patients with juvenile idiopathic arthritis: an observational study. [2021]Juvenile idiopathic arthritis (JIA) is a heterogeneous group of idiopathic inflammatory arthritis affecting children younger than 16 years of age. Tocilizumab (TCZ) is a humanized anti-interleukin 6 (IL-6) receptor antibody that was approved for systemic and polyarticular JIA patients. However, the studies regarding patients' satisfaction while receiving TCZ therapy is scarce. Herein, we aimed to evaluate the effect of subcutaneous (SC) TCZ administration on patient satisfaction and disease control of JIA patients.
Efficacy and Safety of Tocilizumab for Polyarticular-Course Juvenile Idiopathic Arthritis in the Open-Label Two-Year Extension of a Phase III Trial. [2021]To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA).
Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy. [2021]Tezepelumab is an anti-thymic stromal lymphopoietin mAb. In the PATHWAY phase IIb study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma.
In severe, uncontrolled asthma, tezepelumab reduced exacerbations and improved asthma control at 1 y. [2021]Label="SOURCE CITATION">Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021;384:1800-9. 33979488.
Tezspire Approved for Severe Asthma. [2023]Tezepelumab-ekko (Tezspire) has been approved by the Food and Drug Administration as an add-on maintenance therapy for people ages 12 years and older with severe asthma symptoms not controlled by current medication.The drug must be given subcutaneously by a health care provider.
Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. [2022]Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. It was approved by the United States Federal Drug Administration (US FDA) as an add-on maintenance treatment for patients with severe uncontrolled asthma in December 2021. We conducted a systematic review and meta-analysis to investigate the safety and efficacy of tezepelumab on forced expiratory volume (FEV1) (L), the rate of asthma exacerbations, health-related quality of life, fractional exhaled nitric oxide (FeNO) (ppb), and blood eosinophil count (cells/mL) in patients with severe, uncontrolled asthma. Mean changes for efficacy and proportions (safety) with their corresponding 95% confidence intervals (CIs) were used to provide pooled estimates. A total of six randomized controlled trials comprising 2667 patients were included, of whom 1610 were treated with tezepelumab and 1057 received placebo. The pooled analysis showed that tezepelumab treatment resulted in an improvement in FEV1 of 0.15 L (95% CI: 0.12 to 0.17), a reduction in the asthma exacerbation rate per year of 0.60 (95% CI: 0.51 to 0.70), and a reduction in FeNO of -12.41 ppb (95% CI: -14.28 to -10.53) when compared to placebo. Improvements in FEV1 and FeNO levels were maintained at 24 and 52 weeks. As for safety, patients did not experience a higher incidence of adverse drug reactions with tezepelumab (0.79 (95% CI: 0.55 to 1.12)) as compared to placebo. As for quality of life, different doses of the tezepelumab intervention group depicted non-significant improvement in the QoL, from 0.15 (95% CI: -0.09 to 0.38) for 70 mg, 0.18 (95% CI: -0.10 to 0.46) for 210 mg, 0.08 (95% CI: -0.16 to 0.32) for 280 mg as compared to the placebo. Tezepelumab significantly reduced exacerbation rates and improved FEV1 with an acceptable safety profile.
Subcutaneous Tocilizumab in Juvenile Idiopathic Arthritis Associated Uveitis. [2023]To describe the efficacy and safety of subcutaneous tocilizumab (SC-TCZ) in a cohort of juvenile idiopathic arthritis (JIA) patients with refractory uveitis.
Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. [2023]Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin. The drug has been tested previously in the phase 3 NAVIGATOR (NCT03347279) and SOURCE (NCT03406078) studies, and was subsequently approved as a treatment for severe asthma. This extension study recruited from NAVIGATOR and SOURCE and aimed to evaluate the long-term safety and efficacy of tezepelumab in individuals with severe, uncontrolled asthma.
Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials. [2023]Rationale: Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts and fractional exhaled nitric oxide levels, and irrespective of allergy status, in the phase 2b PATHWAY (Study to Evaluate the Efficacy and Safety of MEDI9929 [AMG 157] in Adult Subjects With Inadequately Controlled, Severe Asthma; NCT02054130) and phase 3 NAVIGATOR (Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma; NCT03347279) trials. Objectives: To examine the efficacy and safety of tezepelumab in additional clinically relevant subgroups using pooled data from PATHWAY and NAVIGATOR. Methods: PATHWAY and NAVIGATOR were randomized, double-blind, placebo-controlled trials with similar designs. This pooled analysis included patients with severe, uncontrolled asthma (PATHWAY, 18-75 years old; NAVIGATOR, 12-80 years old) who received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. The annualized asthma exacerbation rate over 52 weeks and secondary outcomes were calculated in the overall population and in subgroups defined by inflammatory biomarker levels or clinical characteristics. Measurements and Main Results: Overall, 1,334 patients were included (tezepelumab, n = 665; placebo, n = 669). Tezepelumab reduced the annualized asthma exacerbation rate versus placebo by 60% (rate ratio, 0.40 [95% confidence interval, 0.34-0.48]) in the overall population, and clinically meaningful reductions in exacerbations were observed in tezepelumab-treated patients with type 2-high and type 2-low disease by multiple definitions. Tezepelumab reduced exacerbation-related hospitalization or emergency department visits and improved secondary outcomes compared with placebo overall and across subgroups. The incidence of adverse events was similar between treatment groups. Conclusions: Tezepelumab resulted in clinically meaningful reductions in exacerbations and improvements in other outcomes in patients with severe, uncontrolled asthma, across clinically relevant subgroups. Clinical trials registered with www.clinicaltrials.gov (NCT02054130 [PATHWAY], NCT03347279 [NAVIGATOR]).
Tezepelumab: an anti-thymic stromal lymphopoietin monoclonal antibody for the treatment of asthma. [2023]Asthma is a common chronic respiratory disease in which epithelial cytokines and airway inflammation play critical pathophysiological roles. Thymic stromal lymphopoietin (TSLP), an epithelial cytokine, is central in the initiation and persistence of airway inflammation in asthma. Tezepelumab is a human immunoglobulin G2λ (IgG2λ) monoclonal antibody developed for treating moderate-to-severe asthma by specifically binding to TSLP and preventing its binding to the TSLP receptor on inflammatory cells. In this narrative review, we describe the results of clinical trials that evaluated the pharmacokinetics, pharmacodynamics, efficacy and safety of tezepelumab in patients with moderate-to-severe asthma. We also introduce the ongoing clinical trials in patients with asthma as well as future trials investigating the use of tezepelumab for other indications.
Secukinumab Therapy in Refractory Juvenile Idiopathic Arthritis. [2023]Juvenile idiopathic arthritis (JIA), the most common chronic rheumatologic condition in childhood, remains a cause of significant morbidity, particularly in those with spondyloarthropathy, including psoriatic arthritis (PsA) and enthesitis-related arthritis (ERA). While secukinumab was recently approved for the treatment of children and adolescents with ERA and PsA, there is limited published data on its use in JIA, particularly in refractory cases, despite its efficacy in the treatment of adult arthritis. We aim to examine the use of this therapy in JIA in a single pediatric rheumatology center. A retrospective chart review was performed and 10 JIA patients who received treatment with secukinumab were identified. Data extracted included disease activity, patient demographics, comorbidities, medications, and laboratory data. Seven ERA, 2 PsA, and 1 poly JIA patient were treated with secukinumab at our center between April 2011 and July 2021. These patients had notably resistant disease, with a mean disease-modifying antirheumatic drug (DMARD) failure rate of 3.8. One hundred percent of patients who underwent magnetic resonance imaging (MRI) after being on at least 3 months of secukinumab therapy demonstrated improvement in their MRI findings. One patient developed a flare of uveitis while on secukinumab therapy, with no other adverse events recorded in our patients. Secukinumab therapy was recently approved for children and adolescents with ERA and PsA, and may offer an efficacious option given its demonstrated improvement in imaging and joint examination, as well as qualitative reports of pain, even in those who have failed other therapies. However, caution may be warranted in those with a history of uveitis and warrants further study.