2024-516689-13-00招募中2 期
A Phase 1b/2 Trial Evaluating the Safety, Pharmacokinetics, and Efficacy of EP 104GI in Adults with Eosinophilic Esophagitis (RESOLVE)
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Frequency and severity of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
Phase 1b: To determine the safety, tolerability, and RP2D(s) and regimen(s) of EP 104GI Phase 1b: To determine the pharmacokinetic (PK) profile of EP 104GI Phase 2: To evaluate the efficacy of EP 104GI on the severity and extent of Eosinophilic Esophagitis (EoE) disease measured by the EoE Histology Scoring System (EoEHSS)
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Follow-up - Phase 2
- 盲法
- Single (Analyst, Subject)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Adults 18 to 75 years of age, inclusive
- •Symptomatic EoE defined as: a. Dose escalation and dose confirmation cohorts: SDI score ≥ 5 at screening and baseline Randomized dose optimization portion: SDI score ≥ 5 at screening and baseline and DSQ total score ≥ 10 over the 14 days prior to screening (at least 11 of 14 days must be completed) b. Confirmed historical diagnosis of EoE with PEC > 15/hpf
- •For women of childbearing potential, a negative pregnancy test (at baseline) and willing to use a highly effective method of birth control between baseline and end of study
- •Willing and able to adhere to study-related procedures and visit schedule
- •Willing and able to provide informed consent
- •Criteria for crossover to EP 104GI from vehicle control (randomized dose optimization portion):
- •Has completed the randomized dose optimization portion of the trial to Week 24, inclusive
- •Without safety concerns for receiving EP 104GI ie, does not meet exclusion criteria or have other safety issue
排除标准
- •Any concomitant esophageal disease and relevant GI disease including but not limited to eosinophilic gastritis or enteritis (defined by clinicopathologic features), erosive esophagitis Los Angeles grade C or higher, Barrett’s esophagus, previous esophageal surgery, Celiac disease, inflammatory bowel disease, or any condition or history of illness or laboratory abnormality that in the investigator’s judgment might interfere with study procedures or ability to complete the study. Note: Participants with occasional gastroesophageal reflux disease (GERD) symptoms without severe (Los Angeles grade C or higher) endoscopic erosive reflux esophagitis are permitted
- •Use of a new inhaled or intranasal corticosteroid within 60 days prior to baseline, or a change in dose of an inhaled or intranasal corticosteroid within 60 days of baseline (a temporary dose change lasting ≤ 14 days is permitted)
- •Initiation of an elimination diet or elemental diet within 30 days prior to baseline (dietary therapy must remain stable throughout the study)
- •Use of biologic immunomodulators in the 90 days prior to baseline
- •Use of immunosuppressive drugs, or potent cytochrome P450 3A4 inhibitors in the 90 days prior to baseline
- •Initiated, discontinued, or changed dosage regimen of PPIs for any condition such as GERD or allergic rhinitis within 4 weeks prior to baseline. Doses must remain stable throughout the study
- •Morning serum cortisol level ≤ 5 μg/dL (138 nmol/L) at Screening visit
- •Use of another investigational product within the 30 days prior to baseline, or an investigational biologic within 90 days prior to baseline, or current/planned participation in another interventional trial during this study
- •Previous participation in this study and had received study treatment
- •Female participants who are pregnant, breastfeeding, or planning to become pregnant during the study
- •The following laboratory values at screening: a. Elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3× upper limit of normal (ULN), bilirubin, alkaline phosphatase (ALP), and/or gamma glutamyl transferase (GGT) > 2× ULN, or creatinine > 1.5× ULN b. Elevated prothrombin time or international normalized ratio > 1.5× ULN c. Hemoglobin A1c (HbA1c) value of ≥ 8.0% (64 mmol/mol) (Note: individuals with insulin dependence or non insulin dependent poorly controlled diabetes will be excluded)
- •Presence of oral or esophageal mucosal infection of any type (bacterial, viral, or fungal)
- •Malignancies or history of malignancy within 5 years of screening, except for adequately treated or completely excised nonmetastatic basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ
- •History of patient reported alcohol or drug abuse within 6 months prior to screening
- •Unwillingness to withhold protocol prohibited medications during the trial
- •Any other reason, including a severe acute or chronic medical or psychiatric condition(s) or laboratory abnormality, that, in the opinion of the investigator, is likely to unfavorably alter participant risk benefit, confound study results, or make it difficult for the participant to fully comply with study requirements
- •Any oropharyngeal or dental condition that prevents normal eating
- •Known severe esophageal motility disorders other than EoE
- •Contraindication to or factors that substantially increase the risk associated with EGD or esophageal biopsy, or narrowing of the esophagus that precludes EGD with a standard 9 10 mm endoscope, stricture requiring dilation within the 8 weeks prior to Screening, or the need for dilation prior to EGD at baseline
- •A history or presence of any condition for which the use of corticosteroids is contraindicated (e.g., insulin dependent diabetes mellitus, Cushing’s syndrome, Addison’s disease, cortisol related endocrinopathy, etc.) Note: Participants with well controlled non insulin dependent diabetes are permitted.
- •Known active or quiescent systemic fungal, bacterial (including tuberculosis), viral (including human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV]), or parasitic infections, or ocular herpes simplex. Or any infection requiring intravenous [IV] antibiotics within 4 weeks of baseline, or oral antibiotics within 2 weeks of baseline
- •Known hypersensitivity, or intolerance to corticosteroids, or to any of the ingredients in the investigational medicinal product, including carboxymethyl cellulose, and polysorbate 80, or to the ingredients in Synacthen / cosyntropin (used in the ACTH stimulation test)
- •Use of systemic corticosteroids within 60 days prior to baseline, or swallowed topical corticosteroids within 60 days prior to baseline, or extended use of high potency dermal topical corticosteroids within 60 days prior to baseline
结局指标
主要结局
Frequency and severity of treatment-emergent adverse events (TEAEs)
Frequency and severity of treatment-emergent adverse events (TEAEs)
Change from baseline in clinical safety laboratory measurements
Change from baseline in clinical safety laboratory measurements
Change from baseline in morning serum cortisol levels 24 hours postdose and timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
Change from baseline in morning serum cortisol levels 24 hours postdose and timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
Change from baseline in vital signs at 1 and 24 hours postdose and timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in).
Change from baseline in vital signs at 1 and 24 hours postdose and timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in).
Plasma concentrations of FP, measured at baseline (predose), 2 and 24 hours postdose, and timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
Plasma concentrations of FP, measured at baseline (predose), 2 and 24 hours postdose, and timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
次要结局
- Change from baseline in EoE Histology Scoring System (EoEHSS) grade and stage scores at timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
- Histological response mapped over the surface of the esophagus as a function of proximity to, and size of dose, measured by peak eosinophil count (PEC) at timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
- Change from baseline in the EoE Endoscopic Reference Score (EREFS) at timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
- Change from baseline in the Straumann Dysphagia Index (SDI) patient reported outcome (PRO) score at timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
- Change from baseline in the Dysphagia symptom questionnaire (DSQ) v4.0 and "Dysphagia days" at timepoints up to 52 Weeks postdose (randomized portion of the study only)
- Change from baseline in Patient Global Impression of Change and Patient Global Impression of Severity (PGIC/PGIS) at timepoints up to 52 Weeks postdose (randomized portion of the study only)
- Change from baseline in dysphagia measured on an 11 point Likert scale at timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
- Change from baseline in odynophagia measured on an 11 point Likert scale at timepoints up to 52 Weeks postdose (dependent on the portion of the study participated in)
- Change from baseline in the Eosinophilic Esophagitis Impact Questionnaire (EOE-IQ) at timepoints up to 52 Weeks postdose (randomized portion of the study only)
研究者
Susan Oakley
Scientific
Eupraxia Pharmaceuticals Inc.
研究点 (2)
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