NCT06023589招募中3 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 231
- 试验地点
- 148
- 主要终点
- Annualized severe asthma exacerbation rate (AAER)
研究概览
简要总结
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.
详细描述
This is a phase-3 multicentre, double-blind, parallel-group placebo-controlled, randomised study.
The study will comprise of:
- Screening/Run-in period of 4 to 6 weeks,
- 52-week double-blind Treatment period,
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-Blind
入排标准
- 年龄范围
- 5 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Documented physician diagnosis of severe asthma confirmed and evaluated for at least 6 months prior to Visit
- •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
- •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
- •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
- •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
- •Pre-BD FEV1 >50% and ≤ 95%PN OR FEV1/forced vital capacity (FVC) ratio ≤ 0.85 at either Visit 1 or Visit
- •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).
排除标准
- •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
- •Change in ICS dose within 1 month prior to Visit
- •History of a life-threatening asthma exacerbation resulting in a hypoxic seizure or requiring intubation.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants will be receiving placebo through a subcutaneous injection
干预措施: Placebo (Other)
Tezepelumab
Experimental
Participants will be receiving tezepelumab subcutaneous injection
干预措施: Tezepelumab (Biological)
结局指标
主要结局
Annualized severe asthma exacerbation rate (AAER)
时间窗: From Baseline to Week 52
To assess the effect of tezepelumab on severe asthma exacerbations in children 5 to \< 12 years old with severe uncontrolled asthma compared with placebo.
次要结局
- Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) percent predicted normal (PN)(From Baseline to Week 52)
- AAER associated with allergic asthma(From Baseline to Week 52)
- Time to first severe asthma exacerbation(From Baseline to Week 52)
- Proportion of participants with ≥ 1 severe asthma exacerbation(From Baseline to Week 52)
- AAER associated with ER visit or hospitalisation(From Baseline to Week 52)
- Change from baseline in weekly mean daily Paediatric Asthma Symptom Observer (PASO) score(From Baseline to Week 52)
- Change from baseline in Asthma Control Questionnaire - Interviewer Administered (ACQ-IA) score(From Baseline to Week 52)
- Change from baseline in weekly mean rescue medication use(From Baseline to Week 52)
- Change from baseline in weekly mean number of night-time awakenings(From Baseline to Week 52)
- Change from baseline in blood eosinophil count(From Baseline to Week 52)
- Change from baseline in fractional exhaled nitric oxide (FeNO)(From Baseline to Week 52)
- Change from baseline in total serum IgE(From Baseline to Week 52)
- Change from baseline in pre-bronchodilator (pre-BD) peak expiratory flow (PEF)(From Baseline to Week 52)
- Number of asthma--related healthcare resource utilization (HRU)(From Baseline to Week 52)
- Number of participant/caregiver health-related absences(From Baseline to Week 52)
- Serum concentrations of tezepelumab(At Baseline, Week 4, Week 24, and Week 52)
- Incidence of anti-drug antibodies (ADAs)(At Baseline, and from time of first dose at Week 0 to end of study at week 64)
- Incidence of neutralising antibodies (nAbs)(At Baseline, and from time of first dose at Week 0 to end of study at week 64)
- Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) percent predicted normal (PN)(From Baseline to Week 52)
- AAER associated with allergic asthma(From Baseline to Week 52)
- Time to first severe asthma exacerbation(From Baseline to Week 52)
- Proportion of participants with ≥ 1 severe asthma exacerbation(From Baseline to Week 52)
- AAER associated with ER visit or hospitalisation(From Baseline to Week 52)
- Cumulative exposure to systemic corticosteroids for treatment of severe asthma exacerbations(From Baseline to Week 52)
- Change from baseline in Paediatric Asthma Quality of Life Questionnaire (PAQLQ-(S)-IA) total score(From Baseline to Week 52)
- Change from baseline in weekly mean daily Paediatric Asthma Symptom Observer (PASO) score(From Baseline to Week 52)
- Change from baseline in Asthma Control Questionnaire - Interviewer Administered (ACQ-IA) score(From Baseline to Week 52)
- Change from baseline in weekly mean rescue medication use(From Baseline to Week 52)
- Change from baseline in weekly mean number of night-time awakenings(From Baseline to Week 52)
- Change from baseline in blood eosinophil count(From Baseline to Week 52)
- Change from baseline in fractional exhaled nitric oxide (FeNO)(From Baseline to Week 52)
- Change from baseline in total serum IgE(From Baseline to Week 52)
- Change from baseline in pre-bronchodilator (pre-BD) peak expiratory flow (PEF)(From Baseline to Week 52)
- Number of asthma--related healthcare resource utilization (HRU)(From Baseline to Week 52)
- Number of participant/caregiver health-related absences(From Baseline to Week 52)
- Serum concentrations of tezepelumab(At Baseline, Week 4, Week 24, and Week 52)
- Incidence of anti-drug antibodies (ADAs)(At Baseline, and from time of first dose at Week 0 to end of study at week 64)
- Incidence of neutralising antibodies (nAbs)(At Baseline, and from time of first dose at Week 0 to end of study at week 64)
研究者
研究点 (148)
Loading locations...
相似试验
已完成
4 期
Effectiveness and Safety Study of Tezepelumab in Adults & Adolescent Participants With Severe Asthma in the United StatesAsthmaNCT05329194AstraZeneca286
已完成
3 期
Clinical Study of Palivizumab in Japanese Newborns, Infants and Young Children at the Age of 24 Months or Less With Immunocompromised Medical ConditionsRespiratory Syncytial Virus InfectionNCT01466062AbbVie (prior sponsor, Abbott)28
进行中（未招募）
3 期
Open-label Study to Assess Reduction of Background Asthma Medication While Sustaining Asthma Control and Clinical Remission With Tezepelumab in Patients 12-80yrs With Severe Asthma.Severe AsthmaNCT06473779AstraZeneca326
已完成
3 期
Study of Ixekizumab (LY2439821) in Children 6 to Less Than 18 Years With Moderate-to-Severe Plaque PsoriasisPlaque PsoriasisNCT03073200Eli Lilly and Company201
已完成
3 期
Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLEStill DiseaseMacrophage Activation SyndromeSecondary Hemophagocytic LymphohistiocytosisSystemic Lupus ErythematosusSJIAMASAOSDNCT05001737Swedish Orphan Biovitrum33