NCT04502862已完成4 期
A Phase 4, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study of the Effect of Dupilumab on Sleep Disturbance in Patients With Uncontrolled Persistent Asthma
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 202
- 试验地点
- 55
- 主要终点
- Change From Baseline to Week 12 in Sleep Disturbance Score Using the Asthma Sleep Disturbance Questionnaire (ASDQ)
研究概览
简要总结
Primary Objective:
To assess the effect of dupilumab on sleep
Secondary Objectives:
- To evaluate the effect of dupilumab on additional participant reported sleep outcomes
- To evaluate the effect of dupilumab on objective sleep assessment
- To evaluate the effect of dupilumab on asthma symptoms
- To evaluate the effect of dupilumab on lung function
- To evaluate the safety of dupilumab
详细描述
Study duration per participant was approximately 16 weeks and up to 29 weeks including up to 5 weeks screening period, a 12-week treatment period and up to 12 weeks post-treatment follow-up period or until the participant switched to commercialized dupilumab (or other biologic product), whichever came first.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Physician diagnosis of asthma based on the Global Initiative for Asthma (GINA) 2020 Guidelines for ≥12 months treated with medium to high dose inhaled corticosteroid (ICS) and a second controller (ie, long-acting beta agonist, leukotriene receptor antagonist). A third controller is allowed but not mandatory. The dose regimen should be stable for at least 1 month before the study and during the screening period
- •History of at least one severe asthma exacerbation within 1 year prior to screening. Severe exacerbation is defined as deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids (oral or injectable)
- •Eosinophils ≥150 cells/μL and fractional exhaled nitric oxide (FeNO) ≥25 ppb during screening, prior to randomization
- •Historical values of blood eosinophil count meeting the eligibility criterion measured within 6 months prior to screening Visit 1 in the absence of oral corticosteroid (OCS) treatment are allowed
- •FeNO value to be checked for eligibility at Visit 2 as well
- •Asthma control questionnaire (ACQ)-5 ≥2.5 at screening Visit 1 and Visit 2, prior to randomization
- •Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) ≤ 80% of predicted normal during screening and at Visit 2, prior to randomization
- •Exhibit bronchodilator reversibility (≥12% and 200 mL improvement in FEV1 post short-acting beta agonist administration) during screening period, prior to randomization, unless reversibility test meeting the inclusion criteria was done within 6 months prior to screening Visit 1
- •Weekly average nocturnal awakenings due to asthma symptoms in the week prior to screening Visit 1 is ≥1
排除标准
- •Current smoker
- •Former smoker for 10 years with a smoking history of >10 pack-years
- •Severe asthma exacerbation during screening, prior to randomization
- •History or clinical evidence of chronic obstructive pulmonary disease (COPD) including Asthma-COPD Overlap Syndrome (ACOS) or any other significant lung disease (eg, lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome)
- •History of or current evidence of clinically significant non-respiratory diseases that in the opinion of the investigator may interfere with the aims of the study or put the participant at undue risk
- •Active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Tuberculosis testing would be performed on a country by country basis, according to local guidelines if required by Regulatory Authorities or ethics boards
- •Diagnosed active endoparasitic infection; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization
- •History of human immunodeficiency (HIV) infection or positive HIV test at screening Visit 1
- •Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before screening
- •Known or suspected immunodeficiency including history of invasive opportunistic infections, despite infection resolution
- •Current evidence of clinically significant oncological disease
- •History of systemic hypersensitivity or anaphylaxis to any biologic therapy
- •Severe uncontrolled depression
- •Sleep disturbances not related to asthma, including sleep apnea, hypersomnia, or insomnia secondary to chronic pain, atopic dermatitis (AD), COPD or other conditions
- •Participant who works night shift (ie, any work between 8 pm and 6 am)
- •Erratic sleep habits, as determined by the Investigator
- •Restless leg syndrome or periodic limb movement disorder
- •Chronic treatment with oral corticosteroid (OCS) for more than 2 weeks before screening Visit 1
- •Participant taking sedative, anxiolytic, or hypnotic treatments, including melatonin, within 3 months before randomization
- •Participant taking systemic sedative antihistamines (excluding newer generations of antihistamines) or theophylline
- •Current treatment with antidepressants, lipophilic beta blockers, clonidine, opioids, or other medications known to interfere with sleep and may confound the study assessments, as determined by the Investigator
- •Participant who has taken biologic therapy (including dupilumab)/systemic immunosuppressant to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc) within 2 months or 5 half-lives before screening Visit 1, whichever is longer
- •Treatment with live (attenuated) vaccine within 4 weeks before screening Visit 1
- •NOTE: For participants who have vaccination with live, attenuated vaccines planned during the course of the study (based on national vaccination schedule/local guidelines), it will be determined, after consultation with a physician, whether the administration of vaccine can be postponed until after the end of the study, (i.e. after the 12 week follow-up period off-treatment or until the participant switches to commercialized dupilumab or other biologic product, whichever comes first), or preponed to before the start of the study without compromising the health of the participant:
- •Participant for whom administration of live (attenuated) vaccine can be safely postponed would be eligible to enroll into the study
- •Participant who have their vaccination preponed can enroll in the study only after a gap of 4 weeks following administration of the vaccine
- •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
Dupilumab
Experimental
Participants received a loading dose of 400 mg of dupilumab (2 injections × 200 mg) SC on Day 1, followed by 200 mg Q2W for 12 weeks.
干预措施: SAR231893 (Drug)
Placebo
Placebo Comparator
Participants received an initial loading dose of matching placebo (2 injections of placebo) SC on Day 1, followed by 1 injection of placebo Q2W for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to Week 12 in Sleep Disturbance Score Using the Asthma Sleep Disturbance Questionnaire (ASDQ)
时间窗: Baseline (Day -6 to Day 1) up to Week 12
The ASDQ is a participant-reported outcome (PRO) measure designed to assess the impact of asthma on participants' sleep. Participants were instructed to record the severity of the disturbance of their sleep due to asthma as: 0 = slept through the night, no asthma symptoms; 1 = slept well, no night time awakenings because of asthma, but some asthma symptoms in the morning; 2 = woke up once because of asthma (may or may not include early awakening); 3 = woke up several times because of asthma (may or may not include early awakening) and 4 = bad night, awake most of the night because of asthma. The participants recorded their sleep disturbance in an electronic diary, once a day upon awakening. Total scores ranges between 0 to 4 with 0 indicating no impact of asthma on sleep and 4 indicating higher impact of asthma on sleep. Higher scores indicated worse outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.
次要结局
- Change From Baseline to Week 12 on the Number of Nocturnal Awakenings (Sleep Diary)(Baseline (Day -6 to Day 1) up to Week 12)
- Change From Baseline to Week 12 in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment 8a Scale(Baseline (Day 1) up to Week 12)
- Change From Baseline to Week 12 in Sleep Quality (Sleep Diary)(Baseline (Day -6 to Day 1) up to Week 12)
- Change From Baseline to Week 12 in Restorative Sleep (Sleep Diary)(Baseline (Day -6 to Day 1) up to Week 12)
- Change From Baseline to Week 12 in Wake After Sleep Onset (WASO) (Sleep Diary)(Baseline (Day -6 to Day 1) up to Week 12)
- Change From Baseline to Week 12 in WASO Based on Actigraphy Data(Baseline (Day -6 to Day 1) up to Week 12)
- Change From Baseline to Week 12 in Asthma Daytime Symptom Diary (ADSD)(Baseline (Day -7 to Day -1) up to Week 12)
- Change From Baseline to Week 12 in Asthma Nighttime Symptom Diary (ANSD)(Baseline (Day -6 to Day -1) up to Week 12)
- Change From Baseline to Week 12 in Pre-Bronchodilator Forced Expiratory Volume (Pre-BD FEV1)(Baseline (Day 1) up to Week 12)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events Of Special Interest (TEAESIs)(From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs(From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks)
研究者
研究点 (55)
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