A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 321
- 试验地点
- 3
- 主要终点
- Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24
研究概览
简要总结
The primary objectives of the study by study part are:
Part A:
To determine the treatment effect of dupilumab compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures and to inform/confirm the final sample size determination for Part B.
Part B:
To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures.
Part C:
To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with EoE after up to 52 weeks of treatment as assessed by histological and clinical measures.
The secondary objectives of the study are:
- To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent patients with EoE
- To explore the relationship between dupilumab concentration and responses in adult and adolescent patients with EoE, using descriptive analyses
- To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation
- To demonstrate the efficacy of dupilumab treatment compared to placebo after 24 weeks and 52 weeks of treatment in adult and adolescent patients with EoE who have previously received swallowed topical corticosteroids
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A: Dupilumab or Placebo
Part A consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.
干预措施: Dupilumab (Drug)
Part A: Dupilumab or Placebo
Part A consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.
干预措施: Placebo (Drug)
Part B: Dupilumab or Placebo
Part B consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab dosing regimen 1, dupilumab dosing regimen 2 or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.
干预措施: Dupilumab (Drug)
Part B: Dupilumab or Placebo
Part B consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab dosing regimen 1, dupilumab dosing regimen 2 or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.
干预措施: Placebo (Drug)
Part C: Dupilumab
Part C is a 28-week extended active treatment period. Participants will receive dupilumab dosing regimen 1, dupilumab dosing regimen 2. At the end of the treatment period (week 52), participants will enter a 12-week follow-up period.
干预措施: Dupilumab (Drug)
结局指标
主要结局
Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24
时间窗: Baseline and week 24
The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils Per High-power Field (Eos/Hpf) in All Three Regions at Week 24
时间窗: At week 24
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
次要结局
- Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24(Baseline and week 24)
- Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by EoE Impact Questionnaire (EoE-IQ) at Week 24(Baseline and week 24)
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24(At week 24)
- Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24(Baseline and week 24)
- Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24(Baseline and week 24)
- NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24(Baseline and week 24)
- Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24(At week 24)
- Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52(Baseline (of previous study part) and week 52)
- Percent Change From Baseline in DSQ Total Score at Week 24(Baseline and week 24)
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24(At week 24)
- Percent Change in DSQ Total Score at Week 52(Baseline (of previous study part) and week 52)
- Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24(Baseline and week 24)
- Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24(Baseline and week 24)
- Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24(Baseline and week 24)
- Absolute Change From Baseline in Esophageal Distensibility Plateau Measured by Functional Lumen Imaging, if Collected, at Week 24(At week 24)
- Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24(Baseline and week 24)
- Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52(Baseline (of previous study part) and week 52)
- Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52(Baseline (of previous study part) and week 52)
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52(At week 52)
- NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52(Baseline (of previous study part) and week 52)
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils Per High-power Field (Eos/Hpf) in All Three Regions at Week 52(At week 52)
- Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52(Baseline (of previous study part) and week 52)
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52(At week 52)
- Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52(Baseline (of previous study part) and week 52)
- Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52(Baseline (of previous study part) and week 52)
- Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period(Baseline (of Part C) to week 28)
- Absolute Change in EoEHSS Mean Stage Score at Week 52(Baseline (of previous study part) and week 52)
- Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52(Baseline (of previous study part) and week 52)
- Concentration of Functional Dupilumab in Serum at Week 52(Baseline (of Part C) up to week 52)
- Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response(Baseline (of previous study part) up to week 52)
- NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52(Baseline (of previous study part) and week 52)