Tezepelumab for Severe Asthma in Children

(HORIZON Trial)

Recruiting at 144 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Inhaled corticosteroids

Disqualifiers: Cystic fibrosis, Chronic rhinosinusitis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

231 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment called tezepelumab for children with severe asthma. The goal is to determine if this medication can aid children who use medium to high-dose asthma inhalers and other asthma medications but still struggle to control their symptoms. Participants will receive either tezepelumab or a placebo through an injection under the skin. Children who have had severe asthma for at least six months, frequently experience asthma attacks, and are already on multiple asthma medications may be suitable for this trial. As a Phase 3 trial, this is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for severe asthma.

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.

Is there any evidence suggesting that tezepelumab is likely to be safe for children with severe asthma?

Research has shown that tezepelumab is generally safe for people with severe asthma. In earlier studies, throat irritation, joint pain, and back pain were the most common side effects, affecting about 3% or more of patients. The FDA approved tezepelumab for individuals aged 12 and older with severe asthma, indicating a proven safety record for that age group. This approval suggests that tezepelumab is well-tolerated for its intended use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Tezepelumab is unique because it works by targeting a protein called thymic stromal lymphopoietin (TSLP), which plays a crucial role in the inflammation process of asthma. Unlike standard treatments for severe asthma, which often involve corticosteroids or bronchodilators, tezepelumab offers a new mechanism of action by directly blocking TSLP. This targeted approach has the potential to reduce inflammation more effectively and with fewer side effects. Researchers are excited about tezepelumab because it could offer a more precise treatment option for children with severe asthma, providing better control over symptoms where current options might fall short.

What evidence suggests that tezepelumab might be an effective treatment for severe asthma in children?

Research has shown that tezepelumab, which participants in this trial may receive, helps reduce asthma attacks in people with severe, uncontrolled asthma. Studies have found that it decreases the need for hospital or emergency room visits due to asthma flare-ups. This benefit occurs regardless of blood eosinophil levels, which are markers often linked to severe asthma. Tezepelumab blocks a key pathway that leads to inflammation in asthma, reducing the frequency and severity of asthma symptoms and improving overall breathing health. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tezepelumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Tezepelumab Experimental Treatment 1 Intervention

Participants will be receiving tezepelumab subcutaneous injection

Group II: Placebo Placebo Group 1 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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Tezepelumab significantly reduced annualized asthma exacerbation rates (AAER) by 66% to 78% in patients with perennial allergy and by 67% to 71% in those without, based on a study of 550 adults over 52 weeks.

The treatment also improved lung function (measured by prebronchodilator FEV1) and reduced type 2 biomarkers, demonstrating its efficacy in managing severe, uncontrolled asthma regardless of allergy status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy. Corren, J., Ambrose, CS., Sałapa, K., et al.[2021]

Tezepelumab-ekko (Tezspire) is FDA-approved as an add-on maintenance therapy for individuals aged 12 and older with severe asthma that is not adequately controlled by existing medications.

The administration of Tezspire requires a healthcare provider to give it subcutaneously, highlighting the importance of professional oversight in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezspire Approved for Severe Asthma. Aschenbrenner, DS.[2023]

Tezepelumab is a monoclonal antibody that targets thymic stromal lymphopoietin (TSLP), a key cytokine involved in asthma, and works by blocking TSLP from activating inflammatory cells, which is crucial for managing moderate-to-severe asthma.

Clinical trials have shown that tezepelumab is effective and safe for treating asthma, and ongoing studies are exploring its potential for other medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab: an anti-thymic stromal lymphopoietin monoclonal antibody for the treatment of asthma. Shinkai, M., Yabuta, T.[2023]

In a phase 2 trial involving 436 patients with uncontrolled moderate-to-severe asthma, tezepelumab significantly reduced the annualized rate of asthma exacerbations by 61% to 71% compared to placebo, demonstrating its efficacy in managing asthma symptoms.

Tezepelumab also improved lung function, as indicated by higher forced expiratory volume in 1 second (FEV1) across all dosing groups, with minimal adverse events leading to discontinuation, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab in Adults with Uncontrolled Asthma. Corren, J., Parnes, JR., Wang, L., et al.[2022]

Tezepelumab was found to be effective in reducing asthma exacerbations in adults and adolescents with severe, uncontrolled asthma, as demonstrated in a clinical trial involving a significant number of participants.

The treatment showed a favorable safety profile, with no new safety concerns identified, making it a promising option for patients struggling to manage their asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In severe, uncontrolled asthma, tezepelumab reduced exacerbations and improved asthma control at 1 y. Taleb, AA., Badgett, RG.[2021]

Tezepelumab significantly reduced asthma exacerbations by 60% compared to placebo in a pooled analysis of 1,334 patients from two major trials, demonstrating its efficacy across various subgroups of severe, uncontrolled asthma.

The treatment not only lowered the rate of exacerbations but also decreased related hospitalizations and emergency visits, with a similar safety profile to placebo, indicating it is a safe and effective option for managing severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials. Corren, J., Menzies-Gow, A., Chupp, G., et al.[2023]

Tezepelumab, a monoclonal antibody approved for severe uncontrolled asthma, significantly improved forced expiratory volume (FEV1) by 0.15 L and reduced asthma exacerbation rates by 0.60 per year compared to placebo, based on a meta-analysis of six trials with 2667 patients.

The treatment was found to have an acceptable safety profile, with no higher incidence of adverse drug reactions compared to placebo, indicating it is a safe option for patients with severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. Zoumot, Z., Al Busaidi, N., Tashkandi, W., et al.[2022]

Tezepelumab, a monoclonal antibody for severe asthma, demonstrated a lower incidence of adverse events and serious adverse events over 104 weeks compared to placebo, indicating a favorable safety profile.

The treatment significantly reduced asthma exacerbation rates by 58% in participants from the NAVIGATOR study and by 39% in those from the SOURCE study, showing sustained efficacy in managing severe, uncontrolled asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. Menzies-Gow, A., Wechsler, ME., Brightling, CE., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37015033/

Efficacy of Tezepelumab in Severe, Uncontrolled Asthma Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts and fractional exhaled nitric ...

2. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D5180C00016

A study to investigate the efficacy and safety ... To assess the efficacy and safety of tezepelumab in pediatric participants with severe uncontrolled asthma on medium to high-dose inhaled corticosteroids (ICS)

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05329194

Study Details | NCT05329194 | Effectiveness and Safety ... This is a multicenter, single-arm, open-label, Post-authorization, Phase 4 study to assess the effectiveness of tezepelumab in the United States (US)

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10870853/

Efficacy of Tezepelumab in Severe, Uncontrolled Asthma Tezepelumab reduced exacerbation-related hospitalization or emergency department visits and improved secondary outcomes compared with placebo overall and across ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06023589

NCT06023589 | A Study to Investigate the Efficacy and ... To assess the effect of tezepelumab on severe asthma exacerbations in children 5 to < 12 years old with severe uncontrolled asthma compared with placebo. From ...

6. tezspirehcp.com tezspirehcp.com/severe-asthma/clinical-data-safety/safety

Safety Profile | TEZSPIRE® (tezepelumab-ekko) for Severe ... The most common adverse reactions (incidence ≥ 3%) are: Asthma: pharyngitis, arthralgia, and back pain. Chronic rhinosinusitis with nasal polyps: ...

7. amgen.com amgen.com/stories/2021/12/-/media/Themes/Global/Global/Global/images/migration/stories/2021/12-17-Severe-Asthma-and-TSLP---Fast-Facts/Tezspire-PDUFA-Discovery-Infographic.pdf

(tezepelumab-ekko) This trial tested the efficacy and safety of Tezspire™ in adults and adolescents with severe asthma. When added to SOC† patients.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/761224Orig1s000ChemR.pdf

761224Orig1s000 Tezepelumab is indicated for the add-on maintenance treatment of patients aged 12 years and older with severe asthma. ... Other Names: AMG 157, ...