Safety Management Plan (SMP) — GLPI103-301
| Field | Value |
|---|---|
| Document ID | TMF-SMP |
| Version | 2.0 |
| Status | Final |
| Study No. | GLPI103-301 |
| Sponsor | Virtual Biopharma Inc. |
| Standard | ICH E2A; E6(R3); E2D; CIOMS; 21 CFR 312.32; EU CTR 536/2014 |
| Confidentiality | Confidential — TMF |
Change History
| Version | Date | Author | Summary of Change |
|---|---|---|---|
| 1.0 | 2026-06-29 | Pharmacovigilance | Initial SMP |
| 2.0 | 2026-07-05 | Pharmacovigilance | Full — severity/causality definitions, special situations, unblinding, and expedited-reporting matrix |
1. Definitions and Collection
Adverse events (AE) and serious adverse events (SAE) are defined per ICH E2A. Treatment-emergent AEs (TEAE) are those with onset on or after the first dose. For each event the site records severity (mild/moderate/severe), causality (related/not related to investigational product), seriousness, action taken, and outcome, on the CRF (CRF-301), standardized to the SDTM AE domain and MedDRA-coded.
| Attribute | Categories | Notes |
|---|---|---|
| Severity | Mild / Moderate / Severe | intensity, not seriousness |
| Seriousness | Death · life-threatening · hospitalization/prolongation · disability · congenital anomaly · other medically important | any one criterion = SAE |
| Causality | Related / Not related | investigator's clinical judgement; sponsor may upgrade |
| Expectedness | Expected / Unexpected | vs Reference Safety Information (IB-001 §7) |
2. Adverse Events of Special Interest (AESI)
Gastrointestinal events; acute pancreatitis; thyroid C-cell neoplasia (MTC/MEN2); hypoglycaemia; and cardiovascular/heart-rate effects (APJ mechanism) — each with a targeted follow-up questionnaire and, where relevant, adjudication (PROT-301 §10; RMP suite).
3. SAE and Expedited Reporting
Sites report SAEs to the sponsor within 24 hours of awareness. The sponsor assesses seriousness, causality, and expectedness and performs expedited regulatory/ethics reporting to the timelines below.
| Event | Assessment | Regulatory timeline |
|---|---|---|
| Fatal/life-threatening SUSAR | serious + related + unexpected | 7 calendar days (initial), 8 days follow-up |
| Other SUSAR | serious + related + unexpected | 15 calendar days |
| Other SAEs | serious | per protocol/aggregate (DSUR) |
| Safety issues affecting benefit–risk | urgent | without delay to authorities/IECs |
Expedited reports follow CIOMS/E2B(R3); expectedness is judged against the IB Reference Safety Information (IB-001 §7).
4. Special Situations
Pregnancy and lactation (report and follow to outcome; treatment stopped), overdose, medication error, lack of efficacy with clinical consequence, occupational exposure, and suspected transmission of an infectious agent are collected and reported per E2D even when not otherwise meeting SAE criteria.
5. Unblinding for Safety
Emergency unblinding is available via the IWRS (TMF-RAND) when knowledge of treatment is essential for participant management. Unblinding events are documented; for SUSAR reporting the sponsor unblinds only the affected case as required, preserving the study blind otherwise.
6. Reconciliation and Oversight
SAE reconciliation between the clinical and safety databases is completed before database lock. An independent DSMB provides periodic unblinded safety oversight per its charter (TMF-DSMB), and can recommend modification or stopping.
7. Signal Detection and Periodic Reporting
Ongoing signal detection (Signal Management Plan, SIGNAL-001) and periodic aggregate reporting — DSUR during development (DSUR-001) and PSUR/PBRER post-authorization (PSUR-001) — are performed consistent with the RMP suite (RMP-EU/US/KR).