A Randomized, Placebo-controlled, Double-blind Trial Evaluating the Efficacy, Tolerability and Safety of ESO-101 in Adult Patients With Active Eosinophilic Esophagitis

EsoCap AG17 个研究点分布在 5 个国家目标入组 43 人2021年6月29日

适应症Eosinophilic Esophagitis

干预措施ESO-101 Placebo

概览

阶段: 2 期
干预措施: ESO-101
疾病 / 适应症: Eosinophilic Esophagitis
发起方: EsoCap AG
入组人数: 43
试验地点: 17
主要终点: Absolute change in peak eosinophil count from Baseline to end of treatment
状态: 已完成
最后更新: 2年前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This is a randomized, placebo-controlled, double-blind trial to evaluate the efficacy, tolerability, and safety of ESO-101 in adult patients with active eosinophilic esophagitis (EoE). Patients will be screened at 2 visits (Visit 1 and Visit 2) during which their eligibility will be assessed based on endoscopy-independent criteria (Visit 1) and based on the histologic assessment of esophageal biopsy samples taken during the screening endoscopy (Visit 2). Eligible patients will be randomized 2:1 to once-daily treatment with ESO-101 or placebo and treated for 28 days starting on Day 0. Further clinic visits will be performed at Day 14 (Visit 4) and Day 28 (Visit 5, end of treatment) to assess the efficacy, tolerability, and safety. In addition, a safety follow-up call will be scheduled 2 weeks after the end of treatment (Day 42, Visit 6).

注册库

clinicaltrials.gov

开始日期

2021年6月29日

结束日期

2023年10月9日

最后更新

2年前

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

EsoCap AG

责任方

Sponsor

入排标准

入选标准

•Adult patients aged 18-70 years;
•Confirmed clinicopathological diagnosis of EoE (eosinophilic esophagitis);
•Active and symptomatic EoE, defined as:
•peak eosinophil count ≥15 eosinophils/high-powered field (hpf) at 2 levels of the esophagus at the screening endoscopy (Visit 2) as measured in a total of 6 hpfs derived from 6 biopsies, 2 each from the proximal, mid, and distal segment of the esophagus;
•either a dysphagia or odynophagia severity sore of ≥4 on a 11-point numeric rating scale for ≥1 day during the 7 days before Screening (Visit 1);
•Written informed consent;
•Willingness and ability to comply with the protocol for the duration of the trial;
•Negative pregnancy test at Screening (Visit 1) and Day 0 (Visit 3) in women of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy);
•Women of childbearing potential must be willing to use (for a least 3 monthly cycles before the screening endoscopy \[Visit 2\] and until 4 weeks after the last intake of IMP) a highly effective method of contraception or birth control (failure rate less than 1% per year when used consistently and correctly). Reliable methods for this trial are:
•combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal);

排除标准

•Women who are pregnant, lactating, possibly pregnant or planning a pregnancy during the trial period;
•Current or past (within the last 3 months) alcohol or drug abuse;
•Initiation of a diet-modifying food restriction within 4 weeks before the screening endoscopy (Visit 2) until EOT (end of treatment);
•Use of systemic corticosteroids or biologic immunomodulators within 3 months before the screening endoscopy (Visit 2) until the EOT;
•History of non-response to treatment of EoE with topical corticosteroid drugs (defined as no improvement of clinical symptoms of EoE after a minimum of 4 weeks corticosteroid therapy used at appropriate doses according to the investigator's judgment) or requirement of cessation of corticosteroid therapy for EoE treatment due to oral candidiasis or systemic corticosteroid side effects;
•Use of corticosteroids for treatment of EoE within 4 weeks before the screening endoscopy (Visit 2) until the EOT;
•Use of inhalable (pulmonary or nasal) corticosteroids within 4 weeks before the screening endoscopy (Visit 2) until the EOT;
•Asthma requiring corticosteroid therapy in the seasonal allergy period according to the investigator's judgment based on anamnesis until the EOT;
•Change in proton pump inhibitor (PPI) dosing regimen within 4 weeks before the screening endoscopy (Visit 2) until the EOT;
•Use of systemic leukotriene receptor antagonists, immunosuppressant therapy, or chronic oral or systemic anticoagulants (such as coumarin derivates, novel oral and subcutaneous anticoagulants) within 2 weeks before Screening (Visit 1) until the EOT;

研究组 & 干预措施

ESO-101

Oral use of 1 hard gelatin capsule (800 μg)

干预措施: ESO-101

Placebo

Oral use of 1 hard gelatin capsule

干预措施: Placebo

结局指标

主要结局

Absolute change in peak eosinophil count from Baseline to end of treatment

时间窗: From Baseline (Visit 2) to end of treatment (Visit 5 = 4-7 weeks after Visit 2)

The processing and analysis of biopsy samples taken at Visit 2 and end of treatment (Visit 5) will be performed blinded at a central laboratory according to a laboratory manual. At both visits, 6 biopsy samples will be taken, 2 each from the proximal, mid, and distal segment of the esophagus. Histology results of the biopsies at Visit 2 will be considered baseline values. For the peak number of eosinophils, hematoxylin and eosin stained esophageal biopsy specimen will be assessed and the high-powered fields with the highest density of eosinophils will be counted.

次要结局

Proportion of patients with a relative reduction in peak eosinophil count of ≥50 percent from Baseline to end of treatment(From Baseline (Visit 2) to end of treatment (Visit 5 = 4-7 weeks after Visit 2))
Proportion of patients with histological remission, defined as the reduction of peak eosinophil count in all esophageal samples to <15 eosinophils/hpf at end of treatment, overall and determined differentially in each of the 3 esophageal segments(From Baseline (Visit 2) to end of treatment (Visit 5 = 4-7 weeks after Visit 2))
Proportion of patients with a relative reduction in peak eosinophil count of ≥30 percent from Baseline to end of treatment(From Baseline (Visit 2) to end of treatment (Visit 5 = 4-7 weeks after Visit 2))
Incidence of treatment-emergent Adverse Events(Visit 3 (Day 0) to day 42)
Incidence of treatment-emergent Serious Adverse Events(Visit 3 (Day 0) to day 42)
Absolute change in dysphagia and odynophagia severity scores from Baseline(From Baseline (Visit 3) to end of treatment (Visit 5 = 28 days after Visit 3))
Relative change in dysphagia and odynophagia severity scores from Baseline(From Baseline (Visit 3) to end of treatment (Visit 5 = 28 days after Visit 3))
Patient-reported treatment satisfaction at end of treatment based on questions about handling, taste, and time necessary for administration(At end of treatment (Visit 5 = day 28))
Absolute change in mean eosinophil count from Baseline to end of treatment(From Baseline (Visit 2) to end of treatment (Visit 5 = 4-7 weeks after Visit 2))
Proportion of patients with histological remission AND improvement in the dysphagia severity score from Baseline to end of treatment(From Baseline (Visit 2 + 3) to end of treatment (Visit 5 = 4-7 weeks after Visit 2))
Incidence of AESI(Visit 2 (day -21 to -1) to Visit 6 (day 42))
Proportion of patients with a peak eosinophil count in all esophageal samples of <6 eosinophils/hpf at end of treatment, overall and determined differentially in each of the 3 esophageal segments(End of treatment (Visit 5 = day 28))
Proportion of patients with an improvement in the dysphagia severity score from Baseline to end of treatment(From Baseline (Visit 3) to end of treatment (Visit 5 = 28 days after Visit 3))
Relative change in mean eosinophil count from Baseline to end of treatment(From Baseline (Visit 2) to end of treatment (Visit 5 = 4-7 weeks after Visit 2))
Proportion of patients with a relative reduction in peak eosinophil count of ≥75 percent from Baseline to end of treatment(From Baseline (Visit 2) to end of treatment (Visit 5 = 4-7 weeks after Visit 2))
Time to achieve symptom relief (defined as 50 percent improvement in the dysphagia or odynophagia symptoms on an NRS compared to Baseline)(From Baseline (Visit 3) to end of treatment (Visit 5 = 28 days after Visit 3))
Change in the EREFS from Baseline to end of treatment(From Baseline (Visit 2) to end of treatment (Visit 5 = 4-7 weeks after Visit 2))
Local tolerability(From Baseline (Visit 3) to end of treatment (Visit 5 = 28 days after Visit 3))