A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Longterm Safety of Dupilumab in Children 2 to <6 Years of Age With Uncontrolled Asthma and/or Recurrent Severe Asthmatic Wheeze
试验速览
- 阶段
- 3 期
- 状态
- Enrolling By Invitation
- 发起方
- Sanofi
- 入组人数
- 90
- 试验地点
- 147
- 主要终点
- Part A: Annualized rate of severe asthma exacerbations during the 52-week treatment period
研究概览
简要总结
This is a parallel, Phase 3, 2-arm study to evaluate the efficacy and long-term safety of dupilumab treatment in children 2 to <6 years of age with uncontrolled asthma and/or recurrent severe asthmatic wheeze. The study will be conducted in 2 parts. Part A will be a 52-week, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of dupilumab in children aged 2 to <6 years old with uncontrolled asthma and/or recurrent severe asthmatic wheeze. At the end of Part A, all eligible participants will be offered participation in Part B, an optional open-label extension phase.
Study details include:
Part A:
The study duration of part A will be up to 68 weeks consisting of a 4-week Screening, a 52week treatment period, and a 12-week post-treatment follow-up period. For participants who will chose to participate in Part B, the study duration will be up to 120 weeks (additional 52-week treatment period).
Part B:
For participants who will choose to participate in Part B, the study duration will be up to 120 weeks (Part A [4-week Screening and a 52-week treatment period] plus additional 52-week treatment period and a 12-week post-treatment follow-up period).
详细描述
The duration per participant is up to 120 Weeks.
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)
入排标准
- 年龄范围
- 2 Years 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 2 to <6 years of age
- •Diagnosis of asthma or recurrent severe asthmatic wheeze that is not controlled with chronic ICS for at least 3 months with stable use of at least low dose ICS for ≥1 month prior to Screening Visit 1 with evidence of uncontrolled asthma and/or recurrent severe asthmatic wheeze.
- •At least one additional major criterion from the modified asthma predictive index:
- •Physician diagnosed Atopic Dermatitis,
- •Allergic sensitization to at least 1 aeroallergen (with a positive serum IgE defined as a value ≥0.35 kU/L).
- •OR 2 minor criteria:
- •Wheezing unrelated to colds,
- •Peripheral blood eosinophilia ≥4%,
- •Allergic sensitization to milk, eggs, or peanuts (defined by serum specific IgE >0.35 kU/L.
- •Parent(s)/caregiver(s)/legal guardian(s) willing and able to comply with clinic visits and study-related procedures.
- •Parent(s)/caregiver(s)/legal guardian(s) able to understand the study requirements.
- •Participants/parent(s)/caregiver(s)/legal guardian(s), as appropriate, must be able to understand and complete study-related questionnaires
- •Body weight at screening and randomization >5 kg and <30 kg.
- •Parents or caregivers or legal guardian capable of giving signed informed consent.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Severe asthma with the need for chronic oral/systemic corticosteroid use (>1 month continuous) at the time of screening enrollment.
- •History of a systemic hypersensitivity reaction or anaphylaxis to biologic therapy, including any excipient.
- •History of prematurity (<34 weeks gestation).
- •Any other chronic lung disease that would impair lung function (eg, cystic fibrosis, bronchopulmonary dysplasia) or chronic lung disease of prematurity or need for oxygen for more than 5 days in the neonatal period.
- •History of life-threatening asthma (eg, requiring intubation).
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Placebo
Placebo matching dupilumab subcutaneous injection as per protocol
干预措施: Placebo (Drug)
Dupilumab (double-blind period)
Dupilumab subcutaneous injection as per protocol
干预措施: Dupilumab (Drug)
结局指标
主要结局
Part A: Annualized rate of severe asthma exacerbations during the 52-week treatment period
时间窗: Baseline through Week 52
Annualized rate of severe asthma exacerbations during the 52-week treatment period.
Part B: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and AEs leading to permanent treatment discontinuation
时间窗: Week 52 through Week 116
Incidence of TEAEs, SAEs, AESIs, and AEs leading to permanent treatment discontinuation.
次要结局
- Part B: Incidence of treatment-emergent anti-drug antibodies (ADAs) against dupilumab over time(Week 52 through Week 104)
- Part A: Annualized rate of hospitalization, ER or urgent care visit for asthma exacerbation during the 52week treatment period.(Baseline through Week 52)
- Part A: Annualized rate of moderate asthma exacerbations during the 52-week treatment period(Baseline through Week 52)
- Part A: Cumulative ICS dose during the 52-week treatment period(Baseline through Week 52)
- Part A: Change from baseline in weekly average use of reliever medication during the 52-week treatment period(Baseline to Week 52)
- Part B: Annualized rate of severe asthma exacerbations events during the 52-week Part B treatment period(Week 52 through Week 104)
- Part B Concentration of dupilumab in serum over time during the 52-week Part B treatment period(Week 52 through Week 104)
- Part A: Mean number of days without asthma symptoms (DWAS) using the Pediatric Asthma Caregiver Diary (PACD) during the 52-week treatment period(Baseline through Week 52)
- Part A: Change from baseline to Week 52 in daytime symptom score using the daytime record of PACD(Baseline to Week 52)
- Part A: Incidence of TEAEs, SAEs, AESIs, and AEs leading to permanent treatment discontinuation(Baseline through Week 52)
- Part A: Change from baseline to Week 52 in Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Scale(Baseline to Week 52)
- Part A: Caregiver Global Impression of Change in their child's asthma control (CGI-change in asthma control) at Week 52(Week 52)
- Part A: Physician Global Assessment of Change of the child's asthma control (PGA-change in asthma control) at Week 52(Week 52)
- Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child's asthma control (CGI-asthma control)(Baseline to Week 52)
- Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child's asthma severity (CGI-asthma severity)(Baseline to Week 52)
- Part A: Change from baseline to Week 52 in Physician Global Assessment of the child's asthma control (PGA-asthma control).(Baseline to Week 52)
- Part A: Change from baseline to Week 52 in Test for Respiratory and Asthma Control in Kids (TRACK)(Baseline to Week 52)
- Part A: Change from baseline in blood eosinophil level at Weeks 24 and 52(Baseline to Week 24 and 52)
- Part A: Concentration of dupilumab in serum over time during the 52-week treatment period(Baseline through Week 52)
- Part A: Incidence of treatment-emergent anti-drug antibody (ADA) against dupilumab over time(Baseline through Week 52)
- Part A: IgG response to any vaccination for tetanus, diphtheria and pertussis and antibody for influenza (HAI antibody titers) vaccine administered according to vaccination schedule during the 52-week treatment period(Baseline through Week 52)