Tezepelumab for Severe Asthma in Children
(HORIZON Trial)
Recruiting in Palo Alto (17 mi)
+104 other locations
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Must be taking: Inhaled corticosteroids
Disqualifiers: Cystic fibrosis, Chronic rhinosinusitis, others
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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop your current medications. However, it requires that participants are on stable doses of their asthma medications for at least one month before starting the trial.
What data supports the effectiveness of the drug Tezepelumab for severe asthma in children?
Tezepelumab has been shown to reduce asthma attacks and improve lung function in patients with severe, uncontrolled asthma. It was approved by the FDA for use in people 12 years and older, and studies have shown it reduces asthma exacerbations and improves breathing without increasing side effects compared to a placebo.12345
How is the drug Tezepelumab different from other treatments for severe asthma in children?
Tezepelumab is unique because it targets thymic stromal lymphopoietin (TSLP), a key molecule involved in airway inflammation, and is administered as an injection by a healthcare provider, unlike many asthma treatments that are inhaled. This makes it particularly effective for patients whose asthma is not controlled by standard inhaled medications.12678
Research Team
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've been on a stable dose of an additional asthma controller for over 3 months.
I am between 5 and 11 years old.
I have been diagnosed with severe asthma for at least 6 months.
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Exclusion Criteria
I have a history of cystic fibrosis, primary ciliary dyskinesia, or chronic sinusitis with nasal polyps.
I haven't changed my asthma medication dose in the last month.
I've had a severe asthma attack that led to a seizure or needed a breathing machine.
See 2 more
Trial Timeline
Screening/Run-in
Participants are screened for eligibility to participate in the trial
4 to 6 weeks
Treatment
Participants receive either tezepelumab or placebo administered by subcutaneous injections
52 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Open-label Active Treatment Extension (optional)
Eligible participants may opt into continuation of active treatment with tezepelumab
24 weeks
Treatment Details
Interventions
- Tezepelumab (Monoclonal Antibodies)
Trial OverviewThe 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.
Participant Groups
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 SitePhoenix, AZ
Research SiteTemple, TX
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZeneca
Lead Sponsor
Trials
4491
Patients Recruited
290,540,000+
Amgen
Industry Sponsor
Trials
1508
Patients Recruited
1,433,000+
Founded
1980
Headquarters
Thousand Oaks, USA
Known For
Human Therapeutics
Top Products
Enbrel, Prolia, Neulasta, Otezla
References
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 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.
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.
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.
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]).
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.
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.
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.