A Trial to Evaluate EP-104GI in Adults With Eosinophilic Esophagitis (EoE).

Официальное название

A Phase 1b/2 Trial Evaluating the Safety, Pharmacokinetics, and Efficacy of EP-104GI in Adults With Eosinophilic Esophagitis (RESOLVE)

Обзор

A Phase 1b/2 study to explore the safety, efficacy and pharmacokinetics of EP-104GI in adults with eosinophilic esophagitis (EoE). Endoscopic and histologic assessments will also be evaluated to understand the local effects of EP-104GI on eosinophilic EoE disease activity. Approximately 27 to 33 participants will be enrolled in dose escalation: 3-6 participants per dose cohort. The number of participants enrolled in escalation will depend on the number of dose escalation cohorts evaluated, and dose cohorts needing to be expanded. An additional 10-24 participants will be enrolled in 1 or 2 cohorts of 10-12 participants each at tolerable dose regimen(s) selected based on the accumulated clinical data to identify the recommended phase 2 dose(s) (RP2D). In the Phase 2 randomized dose optimization portion of the study, approximately 120 subjects will be randomized to Dose A (120 mg total dose), Dose B (160 mg total dose), or matching vehicle control, with an overall assignment ratio of 1:1:1. The total number of participants in both portions of the study will be approximately 160. The study involves 8-10 site visits spread over approximately 52 weeks. Participants in an extended PK sub study will have up to 4 additional visits, to a maximum of 108 weeks post-dose. The participants will either receive the active study drug (EP-104GI) or matching vehicle control. Matching vehicle control will be used only in randomized dose optimization portion of the study. Participants randomized to receive vehicle control may receive EP-104GI (Dose A or Dose B) following the completion of Week 24 providing they meet eligibility criteria for crossover to EP-104GI. Participants randomized to receive EP-104GI on Day 0 will not receive EP-104GI or vehicle control at Week 24. The study drug or matching vehicle control will be administered by qualified personnel during an esophagogastroduodenoscopy (EGD) procedure at the Baseline/Dosing visit. Safety will be assessed throughout the study. Blood and urine samples will be collected at site visits for laboratory assessments and to measure plasma levels of EP-104GI. Participants will complete questionnaires to assess symptoms of dysphagia and odynophagia and will undergo 3-5 EGDs with esophageal biopsies at the Baseline, Week 4 (dose escalation phase only), Week 12, Week 24 (randomized dose optimization phase only), Week 26, and Week 52 (randomized dose optimization phase only).

Вмешательства

• Препарат EP-104GI
  Extended-release fluticasone propionate \[FP\] for injectable suspension for gastrointestinal administration, Powder suspended in vehicle
• Другое Matching vehicle control
  A sterile liquid containing sterile water and excipients necessary to prepare a uniform suspension of the powder.

Первичные конечные точки

• Dose Escalation- Incidence of treatment emergent adverse events (TEAEs) [Срок оценки: 52 weeks]
• Dose Escalation- Severity of treatment emergent adverse events (TEAEs) [Срок оценки: 52 weeks]
• Dose Escalation- Change from baseline in morning serum cortisol levels [Срок оценки: 52 weeks]
• Dose Escalation- Plasma concentrations of fluticasone propionate [Срок оценки: 108 weeks]
• Dose Escalation- Change from baseline in physical examination results, BMI and weight change. [Срок оценки: 12 weeks]
• Randomised Dose Optimization- Change from baseline in EoEHSS grade and stage scored in 3 regions of the esophagus within the injection area (proximal, mid, distal) [Срок оценки: 24 weeks]

Вторичные конечные точки (12)

• Dose Escalation- Peak eosinophil count (PEC) [Срок оценки: 36 weeks]
• Dose Escalation- Change from baseline in the Straumann Dysphagia Index (SDI) score [Срок оценки: 52 weeks]
• Dose Escalation- Change from baseline in dysphagia measured on an 11 point Likert scale [Срок оценки: 52 weeks]
• Dose Escalation- Change from baseline in the EoE Endoscopic Reference Score (EREFS) [Срок оценки: 36 weeks]
• Dose Escalation- Change from baseline in odynophagia measured on an 11 point Likert scale [Срок оценки: 52 weeks]
• Dose Escalation- Change from baseline in EoE Histology Scoring System (EoEHSS) score [Срок оценки: 36 weeks]
• Randomised Dose Optimization- Change from baseline in the Straumann Dysphagia Index (SDI) score [Срок оценки: 52 weeks]
• Randomised Dose Optimization- Change from baseline in the Dysphagia symptom questionnaire (DSQ) v4.0 and "Dysphagia days" [Срок оценки: 52 weeks]
• Randomised Dose Optimization- Change from baseline in the Eosinophilic Esophagitis Impact Questionnaire (EoE IQ) [Срок оценки: 52 weeks]
• Randomised Dose Optimization- Change from baseline in the Patient Global Impression of Change (PGIC) [Срок оценки: 52 weeks]
• Randomised Dose Optimization- Change from baseline in the Patient Global Impression of Severity (PGIS) [Срок оценки: 52 weeks]
• Randomised Dose Optimization- Change from baseline in peak eosinophil count (PEC) [Срок оценки: 52 weeks]

Критерии участия

Критерии включения

• Symptomatic EoE;
• For women of childbearing potential, a negative pregnancy test and willing to use a highly effective method of birth control until 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

Критерии исключения

• Concomitant esophageal disease, relevant GI disease, or any condition, history, or laboratory abnormality that might interfere with the study;
• Oral or esophageal mucosal infection of any type (bacterial, viral, or fungal);
• Oropharyngeal or dental conditions that prevents normal eating;
• Severe esophageal motility disorders other than EoE;
• Contraindication to or factors that substantially increase risks associated with EGD or biopsy, or narrowing of the esophagus that precludes EGD with a standard 9-10 mm endoscope, stricture requiring dilation within 8 weeks prior to Screening, or the need for dilation prior to EGD at Baseline;
• Any condition for which the use of corticosteroids is contraindicated (Participants with well controlled non-insulin dependent diabetes are permitted);
• Active or quiescent systemic fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex. Or recent use of IV or oral antibiotics;
• 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);
• Recent use of disallowed medications, or unwillingness to not use disallowed medications during the study;
• Recent initiation of a elimination or elemental diet (dietary therapy must remain stable throughout the study);
• Morning serum cortisol level ≤ 5 μg/dL (138 nmol/L);
• Clinically significant abnormal laboratory values;
• Recent or currently planned participation in another interventional trial ;
• Previous participation in this study and had received study treatment;
• Females who are pregnant, breastfeeding, or planning to become pregnant during the study;
• Malignancies or history of malignancy within prior 5 years, except for treated or excised non-metastatic BCC, SCC of the skin, or cervical carcinoma in situ;
• History of alcohol or drug abuse;
• Any other reason, that, in the Investigator's opinion, unfavorably alters participant risk, confounds results, or prevents the participant from complying with study requirements.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Австралия · 9 центров

• Campbelltown Private Hospital — Sydney
• Mater Hospital Brisbane — Brisbane
• Princess Alexandra Hospital — Brisbane
• Coastal Digestive Health — Maroochydore
• Royal Adelaide Hospital — Adelaide
• Eastern Health Box Hill — Box Hill
• Northern Hospital Epping — Epping
• The Alfred Hospital — Melbourne
• … и ещё 1 центр

Канада · 4 центра

• University of Calgary — Calgary
• UoA - South Edmonton Gastroenterology Research Clinic — Edmonton
• G.I. Research Institute — Vancouver
• McGill University Health Center — Montreal

Великобритания · 4 центра

• Norfolk and Norwich University Hospital — Norwich
• Cardiff and Vale University Health Board-Wales — Cardiff
• Royal Liverpool University Hospital — Liverpool
• St George's University of London — London

Новая Зеландия · 3 центра

• Aotearoa Clinical Trials — Papatoetoe
• Waikato Hospital — Hamilton
• Capital Coast and Hutt — Lower Hutt

Нидерланды · 2 центра

• Amsterdam UMC — Amsterdam
• Erasmus University Medical Center — Holland

Швейцария · 1 центр

• Universitätsspital Zürich — Zurich

Идентификаторы

NCT: NCT05608681 · EP-104IAR-102 (RESOLVE)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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