265. INITIAL RESULTS FROM RESOLVE, A PHASE 1B DOSE-ESCALATION STUDY OF EP-104GI (EXTENDED-RELEASE FLUTICASONE PROPIONATE INTRA-ESOPHAGEAL INJECTION) FOR EOSINOPHILIC ESOPHAGITIS
Bibliographic record
Abstract
Abstract Background Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by inflammation, influx of eosinophils and esophageal remodeling. Therapy for EoE includes swallowed/topical corticosteroids, dupilumab, and dietary elimination; but these are not always effective. EP-104GI is an extended-release fluticasone propionate (FP) intra-esophageal injection being developed as a novel treatment for EoE. EP-104GI consists of coated FP crystals that release locally via diffusion at a pre-defined rate to reduce peak concentrations and prolong therapeutic window. RESOLVE (NCT05608681) is a Phase 1b, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of EP-104GI in patients with EoE. Methods The conservative starting dose of EP-104GI consisted of 1 mg injected at each of 4 sites in 4 quadrants over two ‘rings’ in the esophagus. Dose escalations increase the dose per site and/or number of sites; the second cohort received 1 mg at each of 8 sites. After a single administration of EP-104GI, participants are assessed for up to 24 weeks including adverse events (AEs) and laboratory tests. Efficacy assessments include histological endpoints and patient-reported symptom outcomes including the Straumann Dysphagia Index (SDI). Esophageal biopsies are collected at baseline, Week 4 and Week 12. Results All subjects demonstrated decreased symptom scores compared to baseline, with generally greater responses at the higher EP-104GI dose in Cohort 2 (Fig 1). Histologically, all Cohort 2 patients showed decreases in EoEHSS scores with 2/3 having ≈50% decrease in total grade score and ≈35% decrease in total stage score at Week 4, also, eosinophil counts were reduced by ≈35% at Week 4 and ≈40% at Week 12. Findings from Cohorts 1 and 2 of the ongoing trial include mild-moderate treatment-emergent AEs, the majority occurring on the day of treatment. No AEs were related to EP-104GI. Conclusions The initial results presented here indicate that the novel diffusion-based localized delivery of FP via EP-104GI injection into the esophagus is feasible and safe in patients with EoE and could avoid the side-effects typically associated with swallowed/topical corticosteroids. Efficacy data from the doses studied, although limited at this point, suggest a dose-response relationship with symptom outcomes and also show histologic improvements. These findings support the potential for an interval of at least 6 months between inter-esophageal injections, which may be further extended at the higher doses to be investigated in this study. Recruitment is ongoing.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".