A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Tezepelumab in Patients With Eosinophilic Esophagitis (CROSSING).
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 368
- 试验地点
- 129
- 主要终点
- Change from baseline in DSQ (Dysphagia Symptom Questionnaire) score
研究概览
简要总结
A randomized, double-blind, placebo-controlled multicenter, phase 3 study to evaluate the efficacy and safety of tezepelumab administered subcutaneously (SC) using an accessorized pre-filled syringe (APFS) versus placebo in adult and adolescent patients with eosinophilic esophagitis (EoE).
详细描述
The study consists of a screening period of 2 to 8 weeks and a 52-week randomized double-blind placebo-controlled treatment period. After completion of the treatment period, participants will be eligible to participate in an optional active treatment extension period (lasting for 24 weeks), followed by a 12-week off-treatment safety follow-up period. Participants who will not participate in the extension period will participate in a 12-week off-treatment safety follow-up period following completion of the 52-week treatment period.
This study will randomize approximately 360 participants. The participants will be randomized at 1:1:1 ratio to the 3 treatment arms.
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)
盲法说明
Double-blind
入排标准
- 年龄范围
- 12 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 12 to 80 years of age inclusive, at the time of signing the informed consent/assent.
- •Weight ≥ 40 kg at Visit 1
- •Established diagnosis of EoE with a previous EGD and esophageal biopsy confirming a diagnosis of EoE.
- •Participants who have symptomatic EoE as defined by a history of on average at least 2 episodes of dysphagia (any severity of food going down slowly or being stuck in the throat) per week in the 4 weeks prior to Visit
- •Must remain on a stabilized diet for at least 8 weeks prior to Visit 1 and during the course of the study (stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups).
- •May be on any background PPI and/or STC, during the course of the study, as long as background medications have been stable for at least 8 weeks prior to the screening/run-in period (Visit 1) and there is agreement not to change background medication or dosage unless medically indicated, during the screening/run-in and treatment period.
- •Participants currently on leukotriene inhibitors and/or steroid treatments for asthma or allergies that are inhaled or administered intranasally, must report a stable dose for at least 4 weeks prior to the screening/run-in period (Visit 1).
- •If a medication for EoE (for example PPI and/or STC) is discontinued prior to the screening/run-in, there should be a washout period of at least 8 weeks prior to Visit
- •Discontinuation of any marketed biologic (monoclonal or polyclonal antibody) should have a washout period of 4 months or 5 half-lives prior to Visit 1, whichever is longer.
- •Participants should have previously documented standard of care treatment, which could include PPI and/or STC and/or diet.
排除标准
- •Other gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, celiac disease, eosinophilic enteritis, colitis, diverticulitis, irritable bowel syndrome, or other clinically significant gastrointestinal conditions as per Investigator discretion.
- •Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation at screening.
- •Use of a feeding tube, or having a pattern of not eating solid food >3 days of week. Solid food is defined as food that requires chewing before swallowing.
- •Hypereosinophilic syndrome
- •EGPA vasculitis
- •Esophageal dilation performed within 8 weeks prior to screening.
研究组 & 干预措施
Placebo
Placebo subcutaneous injections, in accessorised pre-filled syringes
干预措施: Placebo (Other)
Tezepelumab Low Dose
Tezepelumab subcutaneous injections, in accessorised pre-filled syringes
干预措施: Tezepelumab (Biological)
Tezepelumab High Dose
Tezepelumab subcutaneous injections, in accessorised pre-filled syringes
干预措施: Tezepelumab (Biological)
结局指标
主要结局
Change from baseline in DSQ (Dysphagia Symptom Questionnaire) score
时间窗: Week 24
The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia.
Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels
时间窗: Week 24
Peak esophageal eosinophil count per HPF determined by histological analysis of 2-4 biopsies from each of the proximal, mid, and distal esophagus.
次要结局
- Change from baseline in EoE EREFS (Endoscopic reference score )(Week 24, Week 52)
- Change from baseline in EoE-HSS (Histologic scoring system) grade score(Week 24)
- Change from baseline in EoE-HSS (Histologic scoring system) stage score(Week 24)
- Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels(Week 52)
- Change from baseline in DSQ (Dysphagia Symptom Questionnaire) score(Week 52)
- Endoscopic response of total EREFS score of 0 to ≤2 with no score > 1 for any of the components and no worsening in any individual component from baseline accross all esophageal levels(Week 52)
- Endoscopic inflammatory remission of EREFS inflammatory subscore (including edema, exudate, and furrows components) of 0 with no worsening in rings or stricture from baseline across all esophageal levels)(Week 52)
- Total endoscopic remission of total EREFS score of 0 across all esophageal levels(Week 52)