End-of-Phase-2 (EOP2) Meeting Briefing Document — GLPI-103
| Field | Value |
|---|---|
| Document ID | MTG-EOP2 |
| Version | 1.0 |
| Status | Final (portfolio) |
| Meeting type | Type B (End-of-Phase-2) — FDA [MOCK] |
| Compound | GLPI-103 (GLP-1 / Apelin [APJ] receptor dual agonist) |
| Sponsor | Virtual Biopharma Inc. |
| Standard(s) | 21 CFR 312.47 · FDA Formal Meetings Guidance (PDUFA VII) · ICH E8(R1) · E9(R1) |
| Confidentiality | Confidential |
[MOCK]Briefing document supporting an End-of-Phase-2 meeting to reach agreement on the design of the pivotal Phase 3 study (GLPI103-301). Phase 2 figures[MOCK].
Change History
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-06-30 | Regulatory Affairs / Clinical | Initial EOP2 briefing document |
1. Meeting Objectives
To reach agreement on the adequacy of the Phase 2 dose-finding data to support the selected Phase 3 doses, and on the design, endpoints, comparator, estimands, and statistical analysis of the pivotal study to support a future NDA.
2. Phase 2 Results Summary (GLPI103-201)
Randomized, double-blind, placebo-controlled dose-finding in 240 T2DM subjects on metformin (PBO/Low/Med/High × 60), 24 weeks. A monotonic dose-response in HbA1c (up to ~−1.8%) and dose-dependent weight loss were observed; cardiometabolic biomarkers (hsCRP, NT-proBNP, HOMA-IR) improved; gastrointestinal AEs were dose-related and titration-manageable (PM-007 §7; CSR-201). Doses for Phase 3: IV 4 mg QW; oral 8 mg QD.
3. Proposed Phase 3 Design (GLPI103-301)
Randomized, double-blind, double-dummy, active-controlled (vs oral semaglutide), 1:1:1, 52 weeks, ~900 subjects with T2DM inadequately controlled on metformin. Primary: HbA1c CFB at Week 52 (superiority). Key secondary (hierarchical): body weight, HbA1c <7.0%, ≥10% weight loss (PROT-301; SAP-301).
4. Statistical Approach
Primary ANCOVA with MMRM as key secondary/longitudinal analysis; estimand framework per ICH E9(R1) (treatment-policy for discontinuation, hypothetical for rescue); fixed-sequence multiplicity control; reference-based MI and tipping-point sensitivity analyses (SAP-301 §3, §7-8).
5. Questions for the Agency
- Does the Agency agree that the Phase 2 dose-response data adequately support the proposed Phase 3 doses (IV 4 mg QW; oral 8 mg QD)?
- Does the Agency agree that oral semaglutide is an acceptable active comparator and that a superiority design on HbA1c CFB at Week 52 is an acceptable basis for an efficacy claim?
- Does the Agency concur with the primary estimand and the handling of intercurrent events (treatment discontinuation, rescue medication, death) per ICH E9(R1)?
- Does the Agency agree with the key secondary endpoint hierarchy and the multiplicity-control strategy?
- Does the Agency agree that the proposed safety database size and AESI/cardiovascular monitoring are adequate to characterize the benefit-risk for the intended population?
- Does the Agency have recommendations on the planned cardiometabolic biomarker substudy to support differentiation claims?
6. Proposed Agreements
Sponsor seeks agreement on Questions 1-5 to finalize the Phase 3 protocol and SAP prior to study start.