A Randomized, Double-blind, Head-to-head Comparison of Dupilumab Versus Omalizumab in Severe Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) and Comorbid Asthma Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 360
- 试验地点
- 87
- 主要终点
- Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test
研究概览
简要总结
Primary Objective
-To evaluate the efficacy of dupilumab compared to omalizumab in reducing the polyp size and improving sense of smell
Secondary Objectives
- To evaluate the efficacy of dupilumab in improving chronic rhinosinusitis with nasal polyps (CRSwNP) symptoms at Week 24 compared to omalizumab
- To evaluate the efficacy of dupilumab in improving CRSwNP total symptom score (TSS) at Week 24 compared to omalizumab
- To evaluate the effect of dupilumab on health related quality of life (HRQoL) at week 24 compared to omalizumab
- To evaluate the efficacy of dupilumab in improving nasal peak inspiratory flow at Week 24 compared to omalizumab
- To evaluate the effect of dupilumab on CRSwNP overall disease severity at Week 24 compared to omalizumab
- To evaluate the safety of dupilumab and omalizumab
详细描述
Study duration per participant will be 38 weeks. The study will comprise 3 periods: 28 days ± 3 days screening and run-in period; 24 weeks Randomized investigational medicinal product (IMP) intervention period; up to 12 weeks 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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Placebo injections will be administered as needed to blind the number of active dupilumab and omalizumab injections
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 (or the legal age of consent in the jurisdiction in which the study is taking place) years of age inclusive, at the time of signing the informed consent.
- •Participants with bilateral sino-nasal polyposis, that despite prior treatment with Systemic corticosteroids (SCS) anytime within the past 2 years; and/or medical contraindication/intolerance to SCS; and/or prior surgery for NP have:
- •An endoscopic bilateral NPS of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) at visit 1; AND
- •Ongoing symptoms of Nasal congestion/blockade/obstruction and loss of smell for at least 8 weeks before screening (Visit 1), AND
- •Nasal congestion/blockade/obstruction and a weekly average severity greater than 1 in the 7 days before randomization (Visit 2) AND
- •loss of smell symptom severity score 2 or 3 at screening (Visit 1) and a weekly average severity of greater than 1 in the 7 days before randomization (Visit 2).
- •Participants with a physician diagnosis of asthma based on the Global Initiative for Asthma (GINA) 2020 treated with low, medium or high dose inhaled corticosteroids (ICS) and a second controller (ie, LABA), a third controller is allowed but not mandatory. The dose regimen was to be stable for at least 1 month before Visit 1 (screening visit) and during the screening and run-in period.
- •Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 or
- •Treatment with intranasal mometasone ≥200 μg once daily (QD) (or equivalent of another INCS) for 1 month prior to Visit 1 and during the run-in period (for CRSwNP).
- •Eligibility as per omalizumab drug-dosing table (serum IgE level ≥30 to ≤1500 IU/mL and body weight ≥30 to ≤150 kg) and ability to be dosed per the dosing table.
排除标准
- •Participants were excluded from the study if any of the following criteria apply:
- •Participants who underwent any sinus intranasal surgery (including polypectomy) within 6 months before Visit
- •Participants who had a sino-nasal surgery changing the lateral wall structure of the nose, making impossible the evaluation of NPS.
- •Participants with conditions/concomitant diseases making them non evaluable at Visit 1 or for the primary efficacy endpoint such as: Antrochoanal polyps, Nasal septal deviation that would occlude at least one nostril, Acute sinusitis, nasal infection, or upper respiratory infection.
- •Severe asthma exacerbation requiring treatment with SCS in the last 4 weeks prior to Visit 1 and during screening.
- •Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study
- •Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drugs within 2 weeks before Visit 1 (screening visit) or during the screening and run-in period.
- •History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Visit 1 (screening visit).
- •Known or suspected immunodeficiency, including history of invasive opportunistic infections
- •Active malignancy or history of malignancy within 5 years before Visit 1 (screening visit), except completely treated in situ carcinoma of the cervix and completely treated and resolved non metastatic squamous or basal cell carcinoma of the skin.
- •History of systemic hypersensitivity or anaphylaxis to dupilumab and omalizumab, including any excipient
- •Treatment with a live (attenuated) vaccine within 4 weeks before Visit 1 (screening visit).
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Dupilumab 300 mg Q2W
Participants received dupilumab 300 milligrams (mg) subcutaneous (SC) injection every 2 weeks (Q2W) for 24 weeks.
干预措施: Dupilumab (Drug)
Dupilumab 300 mg Q2W
Participants received dupilumab 300 milligrams (mg) subcutaneous (SC) injection every 2 weeks (Q2W) for 24 weeks.
干预措施: Placebo (Drug)
Omalizumab 75 to 600 mg Q2W/Q4W
Participants received omalizumab 75 to 600 mg SC injection Q2W/every 4 weeks (Q4W) based on their serum immunoglobulin E (IgE) levels and body weight for 24 weeks.
干预措施: Omalizumab (Drug)
Omalizumab 75 to 600 mg Q2W/Q4W
Participants received omalizumab 75 to 600 mg SC injection Q2W/every 4 weeks (Q4W) based on their serum immunoglobulin E (IgE) levels and body weight for 24 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test
时间窗: Baseline (Day 1) and Week 24
The UPSIT was a 40-item test to quantitatively assess human olfactory function. The UPSIT test consisted of 4 booklets, each containing 10 odorants with 1 odorant per page. The participant was asked to release the odorant by rubbing the brown-strip (contained odorant microcapsules) with the tip of a pencil and to indicate which of 4 words best described the odor. Thus, each participant received a score out of 40 possible correct answers. The total UPSIT score ranged from 0 (loss of smell/anosmia) to 40 (normal sense of smell/normosmia). Higher scores indicated better olfactory function. Positive change from baseline indicated normal olfactory function. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.
Change From Baseline to Week 24 in Nasal Polyp Score
时间窗: Baseline (Day 1) and Week 24
The NPS was assessed by the independent physician to grade the extent/severity of nasal polyps based on evaluation by nasal endoscopy. The NPS scores for each nostril was graded based on polyp size from 0 (no polyps) to 4 (large polyps causing complete obstruction of the inferior nasal cavity). The total NPS score was calculated as the sum of right and left nostril scores and ranged from 0 (no polyps) to 8 (large polyps). Higher scores indicated more extensive or severe nasal polyps. Negative change from baseline indicated less severity of nasal polyps. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.
次要结局
- Change From Baseline to Week 24 in the Loss of Smell Score of the Chronic Rhinosinusitis With Nasal Polyp (CRSwNP) Nasal Symptom Diary(Baseline (average of Day -6 to Day 1) and Week 24)
- Change From Baseline to Week 24 in the Nasal Congestion Score of the Chronic Rhinosinusitis With Nasal Polyp Nasal Symptom Diary(Baseline (average of Day -6 to Day 1) and Week 24)
- Change From Baseline to Week 24 in Total Symptom Score (TSS) Derived From the Chronic Rhinosinusitis With Nasal Polyp Nasal Symptom Diary(Baseline (average of Day -6 to Day 1) and Week 24)
- Change From Baseline to Week 24 in Sino-Nasal Outcome Test 22-Items (SNOT-22) Total Score(Baseline (Day 1) and Week 24)
- Change From Baseline to Week 24 in Sino-Nasal Outcome Test 22-Items: Nasal Domain Score(Baseline (Day 1) and Week 24)
- Change From Baseline to Week 24 in Nasal Peak Inspiratory Flow (NPIF)(Baseline (average of Day -6 to Day 1) and Week 24)
- Change From Baseline to Week 24 in Rhinosinusitis Visual Analogue Scale (Rhinosinusitis VAS)(Baseline (Day 1) and Week 24)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs)(From first dose of study treatment administration (Day 1) up to 98 days after the last dose of study treatment administration (considering the maximum duration of treatment exposure) i.e., up to approximately 329 days)