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📚 Part of the TILA-278 Regulatory Dossier — Reader's Guide. This article shows the live document; edits to the source appear here automatically.
This is a mock / simulation document, made for a portfolio and for learning. The drug (GLPI-103), the sponsor, the people, and the data are all fictional. It is not a real regulatory submission and has no clinical, legal, or regulatory standing. What is real is the shape of the thing — the document structure, the standards it follows, and the analysis methods; the content inside is illustrative.
What it is. Trial Master File operational document for Study TILA278-201.
Why it exists. An operational trial document describing how the trial is run.
How it is produced here. It is an operational trial document — a plan, charter, or template of the kind kept in the Trial Master File. It describes how the trial is run, rather than reporting the trial's results.
Format & governing standard. FDA DSMB guidance
| Field | Value |
|---|---|
| Document ID | TMF-004 |
| Version | 1.0 |
| Compound | TILA-278 (anti-TL1A antagonist / IL-22R agonist bispecific) |
| Standard | FDA DSMB guidance |
| Confidentiality | Confidential |
Trial Master File operational document for Study TILA278-201.
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-07-08 | Clinical Operations | Initial issue |
This charter defines the composition, authority, operating procedures, and communication pathways of the Data Safety Monitoring Board (DSMB; synonymous herein with an independent Data Monitoring Committee [DMC]) established by Virtual Biopharma Inc. (the Sponsor) for Protocol TILA278-201, a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, 12-week induction study of TILA-278 in adults with moderate-to-severe ulcerative colitis (UC).
TILA-278 is a humanized IgG1 bispecific monoclonal antibody administered subcutaneously (SC); one antigen-binding arm is an anti-TL1A (TNFSF15) antagonist and the second arm is an interleukin-22 receptor (IL-22R) agonist. The intended pharmacology couples dampening of TH1/TH17-driven mucosal inflammation and intestinal fibrosis (TL1A antagonism) with promotion of epithelial regeneration and mucosal-barrier repair (IL-22R agonism). Because the dual mechanism is novel and combines immunomodulation with an epithelial-proliferative signal, prospective independent safety oversight is warranted throughout the conduct of TILA278-201.
The DSMB is an independent, multidisciplinary group of experts constituted to safeguard the interests and safety of enrolled subjects, to preserve the integrity and credibility of the trial, and to protect the validity of trial results. The DSMB is the only body with routine access to accumulating unblinded safety data organized by treatment group during the conduct of the study. It is advisory to the Sponsor; the Sponsor retains ultimate decision-making responsibility but will not overrule a DSMB safety recommendation without documented justification and, where applicable, consultation with health authorities and Institutional Review Boards / Independent Ethics Committees (IRB/IEC).
This charter is a controlled document of the Trial Master File (TMF) and has been prepared in a manner consistent with the U.S. FDA guidance Establishment and Operation of Clinical Trial Data Monitoring Committees (2006), ICH E6(R3) Good Clinical Practice (GCP), ICH E9 Statistical Principles for Clinical Trials and its R1 addendum, and the EMA Guideline on Data Monitoring Committees (EMEA/CHMP/EWP/5872/03 Corr). It is finalized and executed before the first subject is randomized.
| Term | Definition |
|---|---|
| ADA | Anti-drug antibody |
| AE / AESI | Adverse event / adverse event of special interest |
| DSMB / DMC | Data Safety Monitoring Board / Data Monitoring Committee |
| eCRF | Electronic case report form |
| GCP | Good Clinical Practice |
| IBD | Inflammatory bowel disease |
| IL-22R | Interleukin-22 receptor |
| IRB / IEC | Institutional Review Board / Independent Ethics Committee |
| IRT | Interactive response technology |
| SAE | Serious adverse event |
| SC | Subcutaneous |
| SUSAR | Suspected unexpected serious adverse reaction |
| TEAE | Treatment-emergent adverse event |
| TL1A (TNFSF15) | TNF-like ligand 1A (tumour necrosis factor superfamily member 15) |
| TMF | Trial Master File |
| UC | Ulcerative colitis |
| USS / SDAC | Unblinded (independent) statistician / Statistical Data Analysis Center |
The DSMB's remit is limited to Protocol TILA278-201. Its focus is subject safety and the ongoing acceptability of the benefit–risk balance in the context of a short-duration (12-week) induction study.
Governing principles:
No formal group-sequential interim efficacy analysis for stopping for benefit is pre-planned in TILA278-201. Accordingly, the DSMB does not conduct efficacy hypothesis testing and does not issue stop-for-benefit recommendations except in the exceptional circumstance of an unequivocal, clinically compelling safety–benefit imbalance (Section 8.4). Efficacy summaries are provided to the DSMB by treatment group solely to allow interpretation of safety findings within the benefit–risk context.
The DSMB comprises three (3) independent voting members with expertise appropriate to the indication, the modality, and the statistical design. Members are appointed by the Sponsor on the basis of relevant expertise and freedom from conflict of interest, and serve for the duration of the study.
| Role | Expertise | Member |
|---|---|---|
| Chair (voting) | Academic gastroenterologist with inflammatory bowel disease (IBD) clinical-trial experience | |
| Voting member | Clinical immunologist / expert in biologic immunomodulator safety | |
| Voting member | Biostatistician experienced in the statistical monitoring of safety in randomized clinical trials |
At least one member has substantive experience with monoclonal-antibody safety, including immunogenicity and infection risk; at least one member is a practicing physician in the therapeutic area able to judge the clinical relevance of accruing UC and colonic findings. The Chair is a physician.
Prior to appointment, each member discloses financial interests (equity, consultancy, honoraria, research funding), intellectual involvement in competing programs, and any personal or professional relationships that could be perceived as a conflict with respect to TILA-278 or Virtual Biopharma Inc. Members:
Each member and each non-voting participant executes a confidentiality agreement and a conflict-of-interest disclosure before receiving any trial data. Disclosures are updated at least annually and whenever circumstances change. Perceived conflicts are reviewed by the Chair and Sponsor; material unresolved conflicts result in recusal or replacement.
Full attendance by all three voting members is the norm and is expected for any meeting at which a stop, pause, arm-termination, or study-termination recommendation may be formulated. The minimum quorum is two of the three voting members, one of whom must be the Chair. Where a meeting proceeds with two members because the third is unavoidably unavailable, the absent member provides written input in advance, and no stop, pause, or arm-/study-termination recommendation is finalized without the participation (in person or in writing) of the biostatistician. Recommendations are reached by consensus wherever possible. Where consensus cannot be reached, a majority vote is recorded together with any minority position and rationale. In the event of a persistent tie (e.g., a two-member session), the Chair's determination governs, and the matter is re-reviewed at the earliest opportunity with full membership. A member who cannot continue is replaced by the Sponsor following the same independence and conflict criteria; incoming members are oriented to this charter and to prior meeting outcomes.
Reports are prepared in two parts. Open (blinded) reports contain pooled or by-blinded-group data and are available to the full DSMB and, where appropriate, to the Sponsor. Closed (unblinded) reports present data by actual treatment group (TILA-278 High, TILA-278 Low, Placebo) and are restricted to the DSMB voting members and the USS/SDAC.
The closed report presents the following by TILA-278 High, TILA-278 Low, and Placebo. Given the 12-week induction duration and scheduled visits at Weeks 0, 2, 4, 8, and 12, particular attention is paid to on-treatment emergence and dose-ordering of events.
| Domain | Content presented by treatment group |
|---|---|
| Exposure | Number randomized/treated, number of SC administrations, subject-weeks of exposure |
| Overall AE burden | Subjects with ≥1 TEAE; TEAEs by system organ class and preferred term; severity; relatedness |
| Serious events | All SAEs (narratives + tabulation); deaths, with investigator causality |
| Discontinuations | Discontinuations of study drug and of study, with reasons (AE vs. lack of efficacy vs. other) |
| Adverse events of special interest (AESIs) | See Section 5.4 |
| Laboratory | Hematology (with attention to anaemia), chemistry incl. hepatic panel (ALT/AST/ALP/total bilirubin, Hy's-law screening), inflammatory markers; shift tables and marked abnormalities |
| Vital signs / local tolerability | Injection-site reactions (frequency, severity, action taken), systemic hypersensitivity events |
| Immunogenicity | ADA incidence/titer and any temporal association with safety events, as available from the tiered assay |
| Efficacy context | By-group summaries of change in modified Mayo score and clinical remission (modified Mayo ≤2, no subscore >1) at scheduled visits, provided solely for benefit–risk interpretation |
Individual-subject data listings (SAEs, deaths, discontinuations, marked lab abnormalities, and AESIs) are provided to support case-level review.
For each scheduled review, a data cutoff date is pre-specified (typically 2–4 weeks before the meeting) to allow cleaning and report generation. Reports are distributed to voting members securely at least five (5) business days in advance. The report specifies the cutoff, data-maturity caveats, and the extent of medical coding and source verification achieved. SAEs and deaths are reported to the DSMB on an expedited basis irrespective of the scheduled review cycle (Section 6.1).
AESIs are pre-defined in light of the mechanism and modality of TILA-278 and are tabulated and reviewed at every closed session:
Given the compressed 12-week induction design and anticipated enrollment cadence toward 900 randomized subjects, periodic reviews are governed by enrollment milestones and by a calendar minimum, whichever occurs first. Proposed schedule (thresholds confirmable at the organizational meeting):
| Review | Trigger (whichever first) | Primary focus |
|---|---|---|
| Organizational | Before first randomization | Charter, plan, conventions |
| Safety Review 1 | ≈150 subjects randomized and having reached the Week 2 visit, or 3 months after first randomization | Early tolerability, injection-site reactions, early SAEs |
| Safety Review 2 | ≈50% enrolled (≈450 randomized), or 3 months after Review 1 | Emerging profile, dose-ordering, AESIs, labs |
| Safety Review 3 | Last subject randomized, or 3 months after Review 2 | Full-cohort on-treatment safety through Week 8+ |
| Ad hoc | As triggered (Section 6.1) | Signal-driven |
The interval between periodic reviews will not ordinarily exceed three (3) months while subjects are on treatment. The DSMB may increase or decrease the frequency of reviews based on the accruing data and will document any change.
Each meeting is organized into up to three sequential parts:
Meetings may be held by secure teleconference/videoconference. Materials are handled on validated, access-controlled systems.
Safety monitoring is primarily descriptive and clinical rather than inferential. The USS/SDAC presents by-group frequencies, rates adjusted for exposure where appropriate, severity/relatedness distributions, laboratory shift and marked-abnormality tables, and case-level listings. Because TILA278-201 does not implement a pre-planned group-sequential efficacy analysis, no alpha is spent on interim efficacy testing and no efficacy stopping boundary is defined.
For safety, formal statistical stopping rules are intentionally limited; the DSMB relies on clinical judgment informed by pre-specified quantitative triggers (Section 8.3). Where the DSMB wishes to characterize a numerical imbalance, the USS/SDAC may provide descriptive confidence intervals or between-group comparisons, understood as flags for clinical review rather than as hypothesis tests. The dose-ordered design (High vs. Low vs. Placebo) is used to assess whether any safety finding is dose-related; the anticipated pharmacology predicts no dose-dependent systemic safety signal, with injection-site reactions as the principal drug-attributable finding, and the DSMB monitors for deviations from this expectation.
After each closed and executive session, the DSMB issues a single primary recommendation to the Sponsor from the categories below.
| # | Recommendation | Typical basis |
|---|---|---|
| 1 | Continue the study without modification | Safety profile and benefit–risk remain acceptable; data adequate |
| 2 | Continue with modification | Acceptable overall, but warranting protocol, monitoring, or informed-consent changes (e.g., enhanced lab surveillance, revised eligibility, updated risk language, additional data) |
| 3 | Temporary suspension / pause of enrollment and/or dosing | An unresolved potential signal requires further data, root-cause assessment, or a focused ad hoc review before continuation |
| 4 | Terminate one treatment arm (e.g., the High-dose group) | An unacceptable dose-specific safety finding while the remainder of the study remains justified |
| 5 | Terminate the study | The benefit–risk balance is no longer acceptable for continued conduct |
The following pre-specified quantitative triggers do not mandate a specific action but require explicit DSMB deliberation and a documented rationale for whichever recommendation is chosen (thresholds confirmable at the organizational meeting):
Consistent with Section 2, the DSMB will not recommend early termination for efficacy. Only in the exceptional case of an unequivocal, clinically overwhelming safety–benefit imbalance rendering continued placebo or continued lower-dose exposure ethically untenable would the DSMB raise a benefit-driven consideration, and then only in conjunction with a safety rationale and full documentation.
After each meeting, the Chair communicates the DSMB's primary recommendation to a designated senior Sponsor representative, ordinarily in writing within five (5) business days, using a standard recommendation memorandum. A recommendation to continue without modification (Category 1) contains no unblinded data. Recommendations in Categories 2–5 provide the rationale in terms sufficient for the Sponsor to act while disclosing the minimum unblinded information necessary; where feasible, the rationale is framed to avoid unblinding the study team. Urgent recommendations (pause, arm termination, study termination, or any recommendation arising from a death or serious signal) are communicated to the Sponsor by the Chair without delay, ahead of the written memorandum.
The Sponsor documents its decision and rationale in response to each recommendation and retains both in the TMF. Where the Sponsor implements a Category 2–5 recommendation, or otherwise as required, it notifies investigators, IRB/IECs, and health authorities in accordance with regulatory obligations and reporting timelines. Should the Sponsor decline to follow a DSMB safety recommendation, the basis is documented and discussed with the DSMB Chair, and health authorities are informed as appropriate.
Two sets of minutes are maintained:
All materials are version-controlled, dated, and retained per the Sponsor's records-retention policy and applicable regulation.
The DSMB's periodic review does not replace the Sponsor's ongoing expedited safety-reporting obligations (e.g., SUSAR reporting consistent with ICH E2A and applicable regional requirements, and aggregate safety reports). The DSMB is informed of relevant expedited reports and of any external safety information affecting the TILA-278 program or the TL1A/IL-22R class, and may factor these into its recommendations.
This charter takes effect on execution by all voting members and the Sponsor and remains in force until the last subject completes the study and the database is locked, or until the study is terminated. Amendments require the agreement of the DSMB Chair and the Sponsor, are version-controlled, and are documented in the TMF; substantive changes (e.g., to composition, review schedule, or stopping guidance) are agreed before implementation and, where they affect subject safety or trial integrity, discussed with health authorities as appropriate. In the event of conflict between this charter and the protocol regarding safety oversight, the DSMB Chair and Sponsor resolve the discrepancy and record the resolution.
The signatories confirm that they have read this charter, agree to its provisions, and will discharge their responsibilities in accordance with it.
| Name | Role | Signature | Date |
|---|---|---|---|
| DSMB Chair (voting) | __________________ | __________ | |
| DSMB Member — Clinical Immunology (voting) | __________________ | __________ | |
| DSMB Member — Biostatistics (voting) | __________________ | __________ | |
| Independent Unblinded Statistician / SDAC lead (non-voting) | __________________ | __________ | |
| Sponsor Representative, Virtual Biopharma Inc. | __________________ | __________ |
Protocol TILA278-201 — TILA-278 (anti-TL1A × IL-22R bispecific humanized IgG1 monoclonal antibody), moderate-to-severe ulcerative colitis. Sponsor: Virtual Biopharma Inc. This Data Safety Monitoring Board Charter is a controlled document of the Trial Master File.