NCT04678856已完成2 期
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Uncontrolled, Chronic Rhinosinusitis Without Nasal Polyposis (CRSsNP)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 71
- 试验地点
- 116
- 主要终点
- Change From Baseline to Week 24 in Opacification of Sinuses Assessed by Computed Tomography (CT) Scan Using the Lund Mackay (LMK) Score in Dupilumab Group
研究概览
简要总结
Primary Objective:
To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on computerized tomography (CT) scan in the dupilumab group only
Secondary Objectives:
- To evaluate the efficacy of dupilumab as assessed by the reduction at Week 24 in sinus opacification on CT scan and sinus total symptom score (sTSS) compared to placebo
- To evaluate the safety and tolerability of dupilumab in CRSsNP patients compared to placebo
- To evaluate the pharmacokinetics (PK) of dupilumab in CRSsNP patients compared to placebo
- Assessment of immunogenicity to dupilumab over time compared to placebo
详细描述
The duration of study for each participant will include 2-4 weeks of screening period, 24-52 weeks randomized investigational medicinal product (IMP) intervention period and 12 weeks of follow-up 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be at least 18 years of age at the time of signing the informed consent form (ICF).
- •Participants must have bilateral inflammation of paranasal sinuses in CT scan with LMK ≥8 and bilateral ethmoid opacification before randomization.
- •Participants must have ongoing symptoms of loss of smell and rhinorrhea (anterior/posterior) of any severity, with or without facial pain/pressure for at least 12 consecutive weeks by Visit
- •Participants must have ongoing symptoms of nasal congestion (NC)/obstruction at least 12 consecutive weeks before Visit 1 and a NC score of ≥ 2 at Visit 1 (day score) and Visit 2 (weekly average score).
- •Participants must have sTSS (NC, rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (day score) and Visit 2 (weekly average score).
- •Participants must have one of the 2 following features:
- •Prior sinonasal surgery (see note at end of section 5.2 for definitions of sinonasal surgery) for CRS,
- •Treatment with systemic corticosteroids (SCS) therapy for CRS as defined by any dose and duration within the prior 2 years before screening (Visit 1) or intolerance/contraindication to SCS.
排除标准
- •Participants with nasal conditions/concomitant nasal diseases such as nasal polyposis in endoscopy at Visit 1 or with history of nasal polyposis etc., making them non-evaluable at Visit 1 or for the primary efficacy
- •Nasal cavity malignant tumor and benign tumors.
- •Forced expiratory volume (FEV1) ≤50% of predicted normal at Visit
- •Radiologic suspicion or confirmed invasive or expansive fungal rhinosinusitis.
- •Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect participation in the study
- •Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
- •Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection
- •Known or suspected immunodeficiency
- •History of malignancy within 5 years before Visit 1, except completely treated in situ carcinoma of the cervix, and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
- •Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit 1 or during the screening period.
- •History of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients.
- •Participants in prior dupilumab clinical trial or have been treated with commercially available dupilumab within 12 months or who discontinued dupilumab use due to adverse event.
- •Participants who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance™, during screening period.
- •Participants on unstable dose of intranasal corticosteroids (INCS) spray 4 weeks prior to Screening Visit (Visit1) and during screening period.
- •Participants who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit
- •Participants who have taken:
- •Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1
- •Any investigational mAb within 5 half-lives prior to Visit 1
- •Anti-IgE therapy (omalizumab) within 4 months prior to Visit
- •Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1
- •Leukotriene antagonists/modifiers unless participant is on a continuous treatment for at least 30 days prior to Visit
- •Initiation of allergen immunotherapy within 3 months prior to Visit 1 or a plan to begin therapy or change its dose during the screening or treatment period.
- •Participants received SCS during screening period (between Visit 1 and Visit 2).
- •Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to Screening Visit (Visit 1).
- •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
Part A and B: Matching placebo
Placebo Comparator
Participants received matching placebo via SC injection q2w for up to 53.2 weeks.
干预措施: Placebo (Drug)
Part A and B: Dupilumab
Experimental
Participants received dupilumab 300 milligrams (mg) via SC injection q2w for up to 53.1 weeks.
干预措施: Dupilumab SAR231893 (Drug)
结局指标
主要结局
Change From Baseline to Week 24 in Opacification of Sinuses Assessed by Computed Tomography (CT) Scan Using the Lund Mackay (LMK) Score in Dupilumab Group
时间窗: Baseline (Day 1) and Week 24
The CT scan LMK staging system represented the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus on each side). The extent of mucosal opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the ostiomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is therefore 12 per side; total score ranges from 0 (normal) to 24 (more opacified), corresponding to the sum of all sinuses and the ostiomeatal unit. Higher score indicated worse outcome. Baseline was defined as the last available value up to randomization date and prior to the first dose of study medication.
次要结局
- Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score(Baseline (Day 1) and Week 24)
- Change From Baseline to Week 24 in Sinus Total Symptom Score (sTSS)(Baseline (Day 1) and Week 24)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs (TESAEs), and TEAEs Leading to Treatment Discontinuation(From the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days)
- Serum Concentration of Dupilumab Over Time(Baseline (Day 1) and Weeks 12, 24 and 52)
- Number of Participants With Antidrug Antibody (ADA) Response to Dupilumab and Positive Neutralizing Antibody (Nab)(Baseline (Day 1) and up to Week 52)
研究者
研究点 (116)
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