Tapering of Biologics in Chronic Rhinosinusitis With Nasal Polyps
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 135
- 试验地点
- 9
- 主要终点
- The percentage of patients achieving sustained partly controlled disease after tapering of biologics for CRSwNP
研究概览
简要总结
The purpose of this study is to investigate the feasibility of extending the dosing intervals of biological therapies while maintaining optimal treatment effects in chronic rhinosinusitis with nasal polyps (CRSwNP).
详细描述
This is an investigator-initiated, independent, national multicenter study with a real-world design and Good Clinical Practice (GCP) monitoring. The study is a randomized controlled drug trial investigating the non-inferiority of extended dosing intervals compared with standard treatment for patients with CRSwNP receiving mepolizumab (100 mg) or dupilumab (300 mg) every 4 weeks. Approximately 135 patients will be enrolled from ear, nose and throat departments in all five regions of Denmark. The study duration is approximately 2.5 years, with each patient followed for 52 weeks.
Randomization At inclusion, patients are randomized 1:1 to the intervention or control group. Randomization is computer-based (REDCap).
Control group Continues dosing of mepolizumab or dupilumab every 4 weeks.
Intervention group Increases to a 6-week dosing interval at baseline, and if response to the biological therapy is maintained, increases to 8-week dosing intervals at the follow-up visit at week 26. Thereafter, dosing every 8 weeks is maintained until the patient completes the trial at week 52. In case of worsening of CRSwNP-related symptoms, the patient reverts to the last effective dosing interval.
Clinical visits Clinical follow-ups are conducted at weeks 0, 12, 26, 38, and 52. The visits at weeks 0, 26, and 52 are already planned as a standard part of biological treatment outside the protocol and include endoscopic rhinoscopy, smell testing, and questionnaires: Sinonasal Outcome Test 22 (SNOT-22), Work Productivity and Activity Impairment (WPAI), and Asthma Control Questionnaire (ACQ). The visits at weeks 12 and 38 are study-specific and include patient-reported symptom severity on a Visual Analogue Scale (VAS), endoscopic rhinoscopy, and completion of questionnaires (SNOT-22, WPAI).
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
- None
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
- •≥18 years of age.
- •Currently receiving treatment with either dupilumab (300 mg) or mepolizumab (100 mg) every four weeks.
- •Having received the biologic at unchanged dosing interval for at least three months.
- •For at least one year during treatment with biologics, the patients' CRSwNP must be categorized as "partly controlled" as defined by presence of 1-2 of the following seven items (also available in EPOS 2020 table in protocol):
- •Nasal blockage: present on most days of the week
- •Rhinorrhoea/postnasal drip: mucopurulent on most days of the week
- •Facial pain/pressure: present on most days of the week
- •Sense of smell: impaired
- •Sleep disturbance or fatigue: present
- •Nasal endoscopy: diseased mucosa
- •Rescue treatment (systemic corticosteroids, ESS, antibiotics): need of 1 course of rescue treatment
- •of which 1-5 will be scored by the patient using VAS (0-10) and noted above 5.
排除标准
- •Patients with excellent response to biologics (0 of the above-mentioned 7 items for partly controlled disease)
- •Patients with no or limited response to biologics (>2 of the above-mentioned 7 items for partly controlled disease)
- •Patients with a cancer diagnosis deemed by the investigator to preclude participation in the trial
- •Patients who, because of language barriers, are not able to understand Danish written information and, thus, are not able to answer questionnaires
- •Patients who currently receive biologics for any other disease (asthma not included)
- •Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
- •Patients who are not eligible because of the investigator's judgement
- •Patients who experience pregnancy during the study will be excluded after an unscheduled visit - active IVF treatment (please see below)
- •Unwillingness to follow the study procedure
研究组 & 干预措施
Increased dosing interval of biological therapy
Increases to a 6-week dosing interval at baseline - of mepolizumab (100 mg via injection pen, subcutaneous injection) or dupilumab (300 mg via injection pen, subcutaneous injection) - and if response to therapy is maintained, increases to 8-week dosing intervals at the follow-up visit in week 26. Thereafter, dosing every 8 weeks is maintained until the patient completes the trial at week 52.
干预措施: increased dosing interval of biological therapy (Drug)
结局指标
主要结局
The percentage of patients achieving sustained partly controlled disease after tapering of biologics for CRSwNP
时间窗: from enrollment (week 0) to week 52.
"partly controlled" as defined by presence of 1-2 of the following 7 items: 1. Nasal blockage: present on most days of the week 2. Rhinorrhoea/postnasal drip: mucopurulent on most days of the week 3. Facial pain/pressure: present on most days of the week 4. Sense of smell: impaired 5. Sleep disturbance or fatigue: present 6. Nasal endoscopy: diseased mucosa 7. Rescue treatment (systemic corticosteroids, ESS, antibiotics): need of 1 course of rescue treatment
次要结局
未报告次要终点
研究者
Elizabeth M. Stevens
national coordinating investigator, and sub-investigator at Rigshospitalet
Rigshospitalet, Denmark