S689 Efficacy and Pharmacokinetic Results From Ongoing Dose Escalation in RESOLVE, a Phase 1b/2a Study of EP-104GI (Extended-Release Fluticasone Propionate Intra-Esophageal Injection) for Eosinophilic Esophagitis
Bibliographic record
Abstract
Introduction: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by inflammation, esophageal eosinophilia, and remodeling. Therapy for EoE includes swallowed/topical corticosteroids, biologics, proton pump inhibitors, and dietary elimination, but these are not always effective. EP-104GI is an extended-release fluticasone propionate (FP) intra-esophageal injection consisting of polymer-coated FP crystals that release drug locally via diffusion at a pre-defined rate to reduce peak concentrations and prolong the therapeutic window. Methods: RESOLVE (NCT05608681) is a Phase 1b/2a, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of EP-104GI in patients with EoE. The starting dose of EP-104GI consisted of 1 mg injected at each of 4 sites in the esophagus (4 mg total dose). Dose escalations increase the dose per site and/or number of sites: the second and third cohorts received 1 mg and 2.5 mg respectively at each of 8 sites and the fourth cohort received 2.5 mg at 12 sites (8, 20, and 30 mg total doses). In these cohorts, participants are assessed for up to 24 weeks. Assessments include Straumann Dysphagia Index (SDI) at Weeks 2, 4, 8, and 24, Peak Eosinophil Count (PEC) at Weeks 4 and 12, plasma concentrations of FP to Week 24 and safety assessments (adverse events [AEs], serum glucose, and cortisol). Additional cohorts are planned to evaluate greater dose per injection site and/or increased number of injections with up to one year follow-up. Results: Cohorts 1-4 (Figure 1) have shown mean decreases in SDI maintained to Week 24 (Cohorts 1 and 2). PK data show increasing FP exposure with dose with the anticipated low initial peak followed by stable concentrations throughout follow-up. Mean PEC at injected sites has declined for Cohorts 2-4 at the latest timepoint currently assessed (Week 12 for Cohorts 2 and 3; Week 4 for Cohort 4). Treatment-emergent AEs have been mild to moderate, not likely related to EP-104GI, and serum glucose and cortisol were stable post-dose. Conclusion: Initial data show novel diffusion-based localized delivery of FP via EP-104GI injection into the esophagus is feasible and safe in patients with EoE, with improvement in symptom outcomes and histological findings. These findings support the potential for extended intervals of at least 6 months between injections. Recruitment is ongoing.Figure 1.: Mean (SE) plasma FP (panel A), mean (SE) change from baseline in SDI (panel B), and mean (SE) PEC score at injection sites (panel C) following a single dose of EP-104GI.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".