NCT04684524已完成3 期
A Randomized Double-blind Placebo-controlled Parallel Group Study Assessing the Efficacy and Safety of Dupilumab in Patients With Allergic Fungal Rhinosinusitis (AFRS)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 62
- 试验地点
- 93
- 主要终点
- Change From Baseline to Week 52 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score
研究概览
简要总结
Primary Objective:
- To evaluate the efficacy of treatment with dupilumab to reduce sinus opacification in a population with allergic fungal rhinosinusitis (AFRS)
Secondary Objectives:
- To evaluate the efficacy of treatment with dupilumab to reduce sinus opacification in a population with allergic fungal rhinosinusitis (AFRS) at Week 24
- To assess the efficacy of dupilumab to reduce the need for rescue treatments
- To evaluate the efficacy of treatment with dupilumab in improving symptoms in AFRS
- To evaluate the efficacy of dupilumab to reduce nasal polyp formation in participants with AFRS
- To evaluate the efficacy of dupilumab in improving overall symptom severity and quality of life in AFRS
- To evaluate the efficacy of dupilumab in improving sense of smell in participants with AFRS
- To explore the effect of dupilumab as assessed by three-Dimensional CT volumetric measurement of the paranasal sinuses
- To evaluate the safety and tolerability of dupilumab when administered to participants with AFRS
- To evaluate the pharmacokinetics (PK) of dupilumab in participants with AFRS
- To characterize the effect of dupilumab on total IgE and specific IgE
- To assess immunogenicity to dupilumab in participants with AFRS
详细描述
The duration of study for each participant will include 2-4 weeks of screening period (2 additional weeks could be allowed), 52 weeks of 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
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must be at least 6 years of age (or the minimum legal age for adolescents in the country of the investigational site) at the time of signing the informed consent.
- •Participants with the diagnosis of AFRS adapted from criteria by Bent and Kuhn (meeting all):
- •IgE mediated inflammatory response to fungal hyphae (specific IgE serology or skin test) Evidence of sensitization to fungus by skin testing (at screening or documented historical positive skin test in the previous 12 months), or positive fungal-specific IgE in serum at screening.
- •Nasal polyposis confirmed by nasal endoscopy at screening.
- •Characteristic CT signs to be performed during screening period and can include any of the below signs as assessed by central reader:
- •hyperdensities
- •bony demineralization
- •bone erosion of sinus
- •Eosinophilic mucin/mucus identified within 5 years prior to screening or at screening with or without positive fungal stain
- •AFRS patients with the following:
- •An endoscopic NPS of at least 2 out of 4 for unilateral polyps or 3 out of 8 for bilateral polyps at Visit 1 (central reading) and Visit 2 (local reading) and,
- •Sinus opacification in CT scan with an LMK score of 9 for patients with unilateral polyps or 12 for patients with bilateral polyps during screening period and,
- •Body weight ≥15 kg
排除标准
- •Patients with nasal conditions/concomitant nasal diseases making them non-evaluable at Visit 1 or for the primary efficacy
- •Nasal cavity malignant tumor and benign tumors.
- •Known of fungal invasion into sinus tissue.
- •Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's 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
- •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.
- •Treatment with commercially available dupilumab within 12 months, participation in prior dupilumab clinical trial, or discontinued dupilumab use due to adverse event.
- •Patients who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance™, during screening period.
- •Patients who are on intranasal corticosteroids (INCS) spray unless they have received stable dose for at least 4 weeks prior to Visit
- •Patients who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit
- •Patients 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 patient 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. - Patients received SCS during screening period. - 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
Matching placebo
Placebo Comparator
Placebo administered every 2 or 4 weeks based on weights
干预措施: Placebo (Drug)
Dupilumab
Experimental
Dupilumab administered every 2 or 4 weeks based on weights
干预措施: Dupilumab SAR231893 (Drug)
结局指标
主要结局
Change From Baseline to Week 52 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score
时间窗: Baseline (Day 1) and Week 52
The LMK score is used to quantify the degree of opacification of each sinus on CT scan. The CT scan LMK staging system represents 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 plus the osteomeatal complex on each side). The extent of sinus opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the osteomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is 12 per side; total score ranges from 0 (normal) to 24 (more opacified) corresponding to the sum of all sinuses and the osteomeatal complexes bilaterally. Higher score indicate worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.
Change From Baseline to Week 52 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score
时间窗: Baseline (Day 1) and Week 52
The LMK score is used to quantify the degree of opacification of each sinus on CT scan. The CT scan LMK staging system represents 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 plus the osteomeatal complex on each side). The extent of sinus opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the osteomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is 12 per side; total score ranges from 0 (normal) to 24 (more opacified) corresponding to the sum of all sinuses and the osteomeatal complexes bilaterally. Higher score indicate worse outcome; a negative change from baseline indicate improvement. Baseline was defined as the last available value before the first dose of study drug.
次要结局
- Change From Baseline to Week 52 in Three-dimensional CT Total Volume Occupied by Disease in All Sinuses(Baseline (Day 1) and Week 52)
- Percentage of Participants Who Received Systemic Corticosteroids (SCS) and/or Underwent or Planned to Undergo Surgery for Allergic Fungal Rhinosinusitis (AFRS) at Week 52(Week 52)
- Change From Baseline to Week 24 in SNOT-22 Total Score(Baseline (Day 1) and Week 24)
- Percent Change From Baseline in Serum Total Immunoglobulin-E (IgE) to Week 52(Baseline (Day 1) and Week 52)
- Change From Baseline to Week 52 in Monthly Average TSS Derived From the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 52)
- Change From Baseline to Weeks 24 and 52 in the Monthly Average Rhinorrhea Score From the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Weeks 24 and 52)
- Change From Baseline to Week 24 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 24)
- Change From Baseline to Week 24 in Endoscopy Nasal Polyp Score (NPS)(Baseline (Day 1) and Week 24)
- 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 Monthly Average Total Symptom Score (TSS) Derived From the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 24)
- Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT)(Baseline (Day 1) and Week 24)
- Change From Baseline to Week 24 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 24)
- Change From Baseline to Week 52 in Endoscopy NPS(Baseline (Day 1) and Week 52)
- Change From Baseline to Week 52 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 52)
- Change From Baseline to Week 52 in 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score(Baseline (Day 1) and Week 52)
- Change From Baseline to Weeks 24 and 52 in Visual Analog Scale (VAS) Rhinosinusitis(Baseline (Day 1) and Weeks 24 and 52)
- Change From Baseline to Week 52 in UPSIT(Baseline (Day 1) and Week 52)
- Change From Baseline to Week 52 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 52)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks)
- Serum Concentration of Dupilumab Over Time(Baseline (Day 1) and Weeks 12, 24 and 52)
- Percent Change From Baseline in Fungal-specific IgE at Week 52(Baseline (Day 1) and Week 52)
- Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Dupilumab(From first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks)
- Change From Baseline to Week 24 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 24)
- Change From Baseline to Week 24 in Endoscopy Nasal Polyp Score (NPS)(Baseline (Day 1) and Week 24)
- 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 Monthly Average Total Symptom Score (TSS) Derived From the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 24)
- Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT)(Baseline (Day 1) and Week 24)
- Change From Baseline to Week 24 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 24)
- Change From Baseline to Week 52 in Endoscopy NPS(Baseline (Day 1) and Week 52)
- Change From Baseline to Week 52 in Monthly Average Nasal Congestion/Obstruction Score From the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 52)
- Change From Baseline to Week 52 in 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score(Baseline (Day 1) and Week 52)
- Change From Baseline to Week 52 in Three-dimensional CT Total Volume Occupied by Disease in All Sinuses(Baseline (Day 1) and Week 52)
- Percentage of Participants Who Received Systemic Corticosteroids (SCS) and/or Underwent or Planned to Undergo Surgery for Allergic Fungal Rhinosinusitis (AFRS) at Week 52(Week 52)
- Change From Baseline to Week 24 in SNOT-22 Total Score(Baseline (Day 1) and Week 24)
- Percent Change From Baseline in Serum Total Immunoglobulin-E (IgE) to Week 52(Baseline (Day 1) and Week 52)
- Change From Baseline to Weeks 24 and 52 in the Monthly Average Rhinorrhea Score From the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Weeks 24 and 52)
- Change From Baseline to Weeks 24 and 52 in Visual Analog Scale (VAS) Rhinosinusitis(Baseline (Day 1) and Weeks 24 and 52)
- Change From Baseline to Week 52 in UPSIT(Baseline (Day 1) and Week 52)
- Change From Baseline to Week 52 in Monthly Average Decreased/Loss of Smell Using the Nasal Symptom Diary(Baseline (Day -7 to Day -1) and Week 52)
- Percent Change From Baseline in Fungal-specific IgE at Week 52(Baseline (Day 1) and Week 52)
- Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to Dupilumab(From first dose of study drug (Day 1) up to end of follow-up per participant, up to approximately 64 weeks)
研究者
研究点 (93)
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