A Study to Investigate the Efficacy and Safety of Tezepelumab Compared With Placebo in Children 5 to < 12 Years Old With Severe Asthma

Официальное название

A Multicentre, Randomised, Double-Blind, Parallel-Group Placebo-Controlled, Phase 3, Efficacy and Safety Study of Tezepelumab in 5 to < 12 Year Old Children With Severe Uncontrolled Asthma (HORIZON)

Обзор

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.

Подробное описание

This is a phase-3 multicentre, double-blind, parallel-group placebo-controlled, randomised study.

The study will comprise of:

1. Screening/Run-in period of 4 to 6 weeks, 2. 52-week double-blind Treatment period, 3. Post-treatment Follow-up period of 12 weeks.

Participants will be randomised 2:1 to receive either tezepelumab or placebo administered by (SC) Subcutaneous injections for 52 weeks (double-blind Treatment period).

There will then be a 12-week off-treatment Follow-up period for participants who do not continue in the optional open-label Active Treatment Extension period.

An optional open-label Active Treatment Extension will allow all eligible participants the opportunity to receive active treatment with tezepelumab. The Active Treatment Extension period of the study will start following the 52-week double-blind Treatment period and will consist of a 104-week open-label Treatment period prior to the 12-week post-treatment Follow-up period.

Вмешательства

• Биопрепарат Tezepelumab
  Participants will be receiving subcutaneous injection of tezepelumab
• Другое Placebo
  Participants will be receiving subcutaneous injection of matching placebo

Первичные конечные точки

• Annualized severe asthma exacerbation rate (AAER) [Срок оценки: From Baseline to Week 52]

Вторичные конечные точки (12)

• Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) percent predicted normal (PN) [Срок оценки: From Baseline to Week 52]
• AAER associated with allergic asthma [Срок оценки: From Baseline to Week 52]
• Time to first severe asthma exacerbation [Срок оценки: From Baseline to Week 52]
• Proportion of participants with ≥ 1 severe asthma exacerbation [Срок оценки: From Baseline to Week 52]
• AAER associated with ER visit or hospitalisation [Срок оценки: From Baseline to Week 52]
• Cumulative exposure to systemic corticosteroids for treatment of severe asthma exacerbations [Срок оценки: From Baseline to Week 52]
• Change from baseline in Paediatric Asthma Quality of Life Questionnaire (PAQLQ-(S)-IA) total score [Срок оценки: From Baseline to Week 52]
• Change from baseline in weekly mean daily Paediatric Asthma Symptom Observer (PASO) score [Срок оценки: From Baseline to Week 52]
• Change from baseline in Asthma Control Questionnaire - Interviewer Administered (ACQ-IA) score [Срок оценки: From Baseline to Week 52]
• Change from baseline in weekly mean rescue medication use [Срок оценки: From Baseline to Week 52]
• Change from baseline in weekly mean number of night-time awakenings [Срок оценки: From Baseline to Week 52]
• Change from baseline in blood eosinophil count [Срок оценки: From Baseline to Week 52]

Критерии участия

Критерии включения

• Written informed consent from (ICF) at least one parent/caregiver (as per local guidelines) and accompanying informed assent from the participant (where the participant is able to provide assent) prior to admission to the study.
• Participants must be 5 to < 12 years of age, at the time of signing the assent form (as applicable per local guidelines) and their caregivers signing the ICF and at Visit 3.
• Documented physician diagnosis of severe asthma confirmed and evaluated for at least 6 months prior to Visit 1.
• Documented physician-prescribed treatment with a total daily dose of either medium or high dose, for at least 3 months with stable dose ≥ 1 month prior to Visit 1.
• Documented treatment with at least one additional maintenance asthma controller medication is required according to local guidelines and standard of care; (long-acting beta agonist, leukotriene receptor antagonist, long-acting muscarinic antagonist) for at least 3 months with stable dose ≥ 1 month prior to Visit 1.
• Supportive evidence of asthma as documented by one of the following:

• Post-BD (albuterol/salbutamol) responsiveness of FEV1 ≥ 10% during Screening (15 to 30 min after administration of 4 puffs of albuterol/salbutamol with a maximum of 12 puffs of reliever medication only if tolerated by the participant) at either Visit 1 or Visit 2.

If (a) is not achieved at Visit 1 or Visit 2, historical documentation by any of the below prior to Visit 1:

• Post-BD responsiveness of FEV1 ≥ 10%.
• Positive methacholine challenge defined as provocative concentration (PC20) of ≤ 16 mg/mL.
• PEF average daily diurnal variability > 13% over a 2-week period.
• Variability of FEV1 ≥ 12% between any two clinical visits.
• Positive exercise challenge test (defined as a fall in FEV1 of > 12%).
• FeNO ≥ 20 ppb despite confirmed ICS maintenance therapy.
• History of at least 2 severe asthma exacerbation events OR 1 severe asthma exacerbation event resulting in hospitalisation within 12 months prior to Visit 1.
• Pre-BD FEV1 >50% and ≤ 95%PN OR FEV1/forced vital capacity (FVC) ratio ≤ 0.85 at either Visit 1 or Visit 2.
• Evidence of uncontrolled asthma, with at least 1 of the below criteria:

• ACQ-IA score ≥ 1.5 at least once during Screening/Run-in, including Visit 3 (prior to Randomisation) for participants ≥ 6 years old at Screening.
• Use of reliever medication, other than as a preventive for exercise induced bronchospasm, on 3 or more days per week for at least 1 week during the Screening/Run-in period.
• Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening/Run-in period.
• Asthma symptoms 3 or more days per week in at least 1 week during the Screening/Run-in period.
• Body weight ≥ 16 kg at Visit 1 (Screening) and Visit 3 (Randomisation).

Критерии исключения

• History of vocal cord dysfunction, cystic fibrosis, primary ciliary dyskinesia, or chronic rhinosinusitis with nasal polyposis.
• History of any clinically significant disease or disorder other than asthma which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• History of a clinically significant deterioration in asthma or asthma exacerbation including those requiring use of systemic corticosteroids or increase in the maintenance dose of oral corticosteroids within 30 days prior to Visit 1.
• Change in ICS dose within 1 month prior to Visit 1.
• History of a life-threatening asthma exacerbation resulting in a hypoxic seizure or requiring intubation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 30 центров

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Идентификаторы

NCT: NCT06023589 · D5180C00016

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗