Clinical Study Report (Abbreviated) — GLPI103-201 (Phase 2 PoC / dose-finding)
| Field | Value |
|---|---|
| Document ID | CSR-201 |
| Version | 3.0 |
| Study No. | GLPI103-201 |
| Compound | GLPI-103 (GLP-1/APJ dual agonist) |
| Sponsor | Virtual Biopharma Inc. |
| Standard | ICH E3 (abbreviated report) |
| Confidentiality | Confidential — portfolio use |
[MOCK — deep-knowledge assumption]No Phase-2 dataset is simulated; values are illustrative and consistent with IB-001, the Phase-3 dose–response, and REF-002.
Change History
| Version | Date | Author | Summary of Change |
|---|---|---|---|
| 1.0 | 2026-06-29 | Clinical / Biostatistics | Initial abbreviated CSR |
| 2.0 | 2026-06-30 | Clinical / Biostatistics | Expanded to fuller ICH E3 structure (ethics, design, dose-response, safety) |
| 3.0 | 2026-07-05 | Clinical / Biostatistics | Submission-grade — added disposition, demographics, dose–response, and safety tables and a limitations section |
1. Synopsis
| Item | Description |
|---|---|
| Design | Phase 2, randomized, double-blind, placebo-controlled, parallel-group dose-finding (PoC) |
| Population | Adults with T2DM on metformin |
| N | 240 (4 arms × 60: placebo, low, medium, high) |
| Duration | 24 weeks (with titration) |
| Primary endpoint | Change from baseline in HbA1c at Week 24 |
| Key secondary | Body weight; HbA1c <7.0%; cardiometabolic biomarkers |
2. Ethics and Study Administration
Conducted per the Declaration of Helsinki, ICH E6(R3) GCP, and applicable regulations, with IRB/IEC approval, written informed consent, and independent DSMB safety oversight. Multicentre (Republic of Korea) [MOCK].
3. Objectives
Establish proof of concept and characterize the dose–response for HbA1c to select the Phase 3 doses; assess body weight, cardiometabolic biomarkers, and safety/tolerability.
4. Investigational Plan
- Design: randomized 1:1:1:1 to placebo, low, medium, and high GLPI-103 on a background of metformin; double-blind for 24 weeks with conservative titration to manage gastrointestinal tolerability.
- Eligibility: adults with T2DM inadequately controlled on metformin (HbA1c 7.0–10.5%); standard GLP-1-class exclusions (personal/family history of MTC/MEN 2, pancreatitis history).
- Endpoints: primary HbA1c CFB at Week 24; secondary body weight, HbA1c <7.0% attainment, cardiometabolic biomarkers (hsCRP, NT-proBNP, HOMA-IR); safety.
- Statistics: dose–response assessed by an ANCOVA model with a pre-specified trend test across ordered doses (MCP-Mod-style dose–response confirmation); the selected dose informed the Phase 3 maintenance dose.
5. Study Subjects and Disposition [MOCK]
| Arm | Randomized | Completed 24 wk | Discontinued |
|---|---|---|---|
| Placebo | 60 | 54 | 6 |
| Low | 60 | 53 | 7 |
| Medium | 60 | 52 | 8 |
| High | 60 | 50 | 10 |
| Total | 240 | 209 | 31 |
Discontinuations were modestly higher at the high dose, predominantly for gastrointestinal tolerability, consistent with the class exposure–tolerability gradient. Baseline characteristics were comparable across arms (mean age ~58 y; HbA1c ~8.2%; BMI ~29 kg/m²).
6. Efficacy Results [MOCK]
| Endpoint at Week 24 | Placebo | Low | Medium | High |
|---|---|---|---|---|
| HbA1c CFB (%) | −0.3 | −1.1 | −1.7 | −2.1 |
| Body-weight CFB (kg) | −0.8 | −3.5 | −6.0 | −8.0 |
| HbA1c <7.0%, % | 12 | 38 | 55 | 68 |
- Primary: a monotonic, statistically significant dose-dependent HbA1c reduction versus placebo, with a significant positive trend across ordered doses (dose–response confirmed), supporting the high dose for the confirmatory study.
- Cardiometabolic: dose-related improvements in hsCRP, NT-proBNP, and HOMA-IR, supporting the APJ-mediated mechanistic hypothesis.
7. Safety Results [MOCK]
The most common adverse events were gastrointestinal (nausea, vomiting, diarrhoea), dose-related and titration-manageable, predominantly mild–moderate. There were no treatment-related serious adverse events and no deaths; laboratory, ECG, and vital-sign parameters showed no clinically significant trends. Hypoglycaemia was infrequent on the metformin background.
8. Discussion and Conclusions
GLPI-103 demonstrated proof of concept with a clear, monotonic dose–response for glycaemic and weight effects and a manageable safety profile, de-risking the program and supporting the Phase 3 doses (GLPI103-301; REF-002). This study was the Gate-3 decision point for major Phase 3 investment (PM-002/PM-003).
9. Limitations
As a 24-week Phase 2 study the report does not address long-term durability or rare events; efficacy estimates are illustrative [MOCK] and were confirmed in the data-anchored pivotal study. Cardiometabolic-biomarker findings are exploratory.