First in Human Study to Assess Safety of VIS649 in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for First in Human Study to Assess Safety of VIS649 in Healthy Subjects (NCT03719443), a randomized phase 1 study. The primary outcome is Overall Summary of Treatment Emergent Adverse Events.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, placebo-controlled, parallel-group, single-ascending-dose, first-in-human study of intravenous VIS649 in healthy subjects. The registry lists quadruple masking. The brief summary also calls the study double-blind, so the masking descriptions in the record are not consistent. The record does not explain the distinction.

The study description says dosing was organized into sequential cohorts and that safety, pharmacokinetic, and pharmacodynamic data from initial cohorts would be assessed. The brief summary describes up to 5 cohorts, 9 subjects per cohort, and a 7:2 randomization ratio. Actual posted safety results are listed for VIS649 Cohorts 1 through 5, pooled placebo, and the Cohort 5 groups described as including vaccine. The planned cohort description and these posted group labels are not identical in scope; the registry record does not explain the difference.

VIS649 was administered intravenously over approximately 1 hour on Day 1, at doses ranging from 0.5 mg/kg up to but not to exceed 20 mg/kg. Placebo was also administered intravenously over approximately 1 hour on Day 1. The record states that no other doses were administered during the study.

The registry reports enrollment of 51. Its brief summary describes a plan to enroll up to 45 subjects. The record gives a study start of 2018-10-09, primary completion of 2019-08-10, and status of completed. It does not report further details about the randomization sequence, allocation concealment, cohort dose assignments, or how the vaccine groups were incorporated into the design.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: No notable events took place between participant enrollment and assignment.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Overall Summary of Treatment Emergent Adverse Events, measured over Baseline to day 112.

The primary outcome is titled “Overall Summary of Treatment Emergent Adverse Events.” It is expressed as a number of events, and the registry describes adverse events, serious adverse events, and drug-related events following VIS649 administration. The stated assessment period is baseline to day 112. Safety severity was assessed using CTCAE v4.0.

Adverse-event monitoring is used in an early-phase study to describe tolerability and identify safety events after exposure. A count can convey how many events were recorded, while the number of participants affected conveys how many people experienced events; those are different summaries and should not be treated as interchangeable. The posted group-level safety information distinguishes serious events from other events and gives counts of affected participants. It does not provide a complete event-level breakdown, a drug-relatedness breakdown, or a single comparative estimate for the primary outcome.

The registry identifies the safety population for this outcome. It does not describe in detail how events were attributed as treatment-emergent or drug-related, how recurrent events were counted, or how severity categories were summarized. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes random allocation, placebo control, a parallel-group model, and quadruple masking. Randomization is intended to make assigned groups comparable in expectation, while masking can reduce some risks of differential care, reporting, or assessment. These are general principles; the record does not report how the allocation sequence was generated or concealed, nor does it explain who was masked or how masking was maintained. The brief summary’s “double-blind” wording differs from the registry’s quadruple-masking designation.

What does a count outcome describe?

The primary outcome is a count-based safety summary covering adverse events, serious adverse events, and drug-related events. Counts may refer to events, whereas the accompanying safety data also report participants affected. One participant can experience more than one event, so an event count and an affected-participant count answer different questions. The record’s outcome title and description do not supply enough detail to reconstruct event-level totals from affected-participant counts.

General statistical context: counts are often interpreted with attention to the amount of observation, the number of people at risk, and whether repeated events from the same person are allowed. If event counts vary more than a simple statistical model expects, over-dispersion can make standard errors too small unless the analysis accounts for it. This is a general consideration, not a description of a method used in this trial. The registry does not report a count model or an approach to repeated events.

Why are the cohort counts not one simple contrast?

The posted results divide the safety data among pooled placebo, several VIS649 cohorts, and groups labeled as Cohort 5 + Vaccine. These are not presented as one matched pair of treatment and control groups with a single effect estimate. The record does not report the dose assigned to each cohort in the safety results, nor does it provide a method for pooling cohorts or comparing them. A pooled summary could answer a different question from a cohort-by-cohort description, especially where cohort composition or dose differs; no such pooling method is reported.

General statistical context: an estimate is a numerical summary of a target contrast, and a confidence interval describes uncertainty around that estimate under the analysis assumptions. The width and interpretation of an interval depend on the data and model. No confidence intervals, standard errors, or comparative effect estimates for the primary outcome are reported in the registry record, so precision cannot be assessed through those measures.

What is reported about the analysis?

The registry identifies the safety population for the primary outcome and gives an assessment period from baseline to day 112. It does not report a detailed statistical analysis plan, a particular hypothesis test, an adjustment method, or an analysis model for the adverse-event summaries. It also reports no analyses under the analysis listing. The posted information is therefore descriptive rather than a reported inferential comparison.

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. They state that the effect to detect is a specified fraction of the observed effect and distinguish participant-per-arm illustrations from total-event illustrations for time-to-event settings. These are general planning assumptions, not the trial’s reported design justification or observed power. The record does not report the trial’s own sample-size justification or provide numerical planning results in the registry record for this analysis.

General statistical context: a planning calculation asks what sample size might be needed under stated assumptions. It does not establish the chance that a completed trial has detected a real effect, and it cannot replace an analysis of observed data. Interpretation also depends on whether the model and assumptions fit the outcome and design. The registry does not report interim analyses, model diagnostics, or procedures for handling multiple safety categories.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome includes multiple safety categories, and the registry notes that it has several categories or time points rather than one reduced comparison. No multiplicity adjustment is reported in the registry record. Without a stated testing strategy, the record does not establish whether any formal tests across categories were planned or how their interpretation would account for multiple comparisons. In this case, no primary-outcome analyses are listed, so there are no reported p-values whose multiplicity-adjusted interpretation can be assessed.

The registry identifies the safety population for the primary outcome, but does not describe the rules used to include or exclude participants from that population. It does not report how missing safety assessments, incomplete follow-up, withdrawals, or unavailable event information were handled. Missing-data methods and the amount of missing data are not reported in the registry record.

General statistical context: multiplicity arises when several outcomes, time points, groups, or hypotheses are examined. A plan may control the chance of false-positive findings across those comparisons, or may treat analyses as descriptive. Missing-data handling can also affect interpretation if the availability of observations is related to participants’ health or treatment. These are general considerations; the registry does not state which approach was used.

The stated safety observation period is baseline to day 112. The record does not provide follow-up completeness by group or explain how participants with shorter observation were handled. Thus, the posted counts should be read as registry-reported descriptive summaries, not as complete comparative evidence with a documented multiplicity or missing-data strategy.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event figures are zero affected participants in pooled placebo and in each listed VIS649 cohort. The record also lists zero deaths for every group. These are the reported observations, not proof that serious events or deaths are impossible. The registry does not provide uncertainty intervals for these counts.

Other adverse-event counts are reported separately from serious events. The listed affected-participant counts are 4 for pooled placebo, 2 for VIS649 Cohort 1, 3 for VIS649 Cohort 2, 3 for VIS649 Cohort 3, 3 for VIS649 Cohort 4, 3 for Placebo Cohort 5 + Vaccine, and 4 for VIS649 Cohort 5 + Vaccine. The group sizes differ, and the groups are not all presented as a single pooled treatment-comparator comparison. The counts therefore should not be read as directly comparable rates.

The primary outcome description includes drug-related events, but the posted safety figures do not give a separate drug-relatedness breakdown. The record also does not give event-level descriptions for the serious-event outcome. These omissions limit what can be concluded from the safety summaries.

12. What the Result Does, and Does Not, Mean

The registry record describes a Phase 1 study of single-dose intravenous VIS649 in healthy subjects and reports safety information through the stated assessment period. Its posted results show no serious adverse events or deaths in the listed groups, alongside non-serious adverse-event affected-participant counts by group. This is a descriptive account of what the registry reports, not evidence of a definitive comparative safety effect.

The study’s first-in-human setting and early-phase design place emphasis on initial safety, tolerability, and pharmacokinetic and pharmacodynamic assessment. The registry describes those aims, but the numerical findings for pharmacokinetic and pharmacodynamic outcomes are not reported in the registry record for this analysis. There is also no reported numerical comparison of VIS649 with placebo for the primary safety outcome.

The results do not establish that VIS649 is safe or unsafe in all settings, nor do they establish how outcomes would compare in people with IgA nephropathy. The study description identifies healthy subjects, and the registry does not report evidence from a patient population in this record. The listed conditions alone do not change the stated study population.

General statistical context: an observed absence of an event in a study does not establish that the underlying risk is zero. Small studies have limited ability to characterize uncommon harms, and the strength of a comparison depends on the number of observations, follow-up, outcome definitions, and uncertainty estimates. The registry does not report the comparative estimates and precision measures needed to quantify those aspects.

The record also does not include enough detail to assess dose-response patterns, because dose assignments are not linked to each posted cohort safety count in the information. The appropriate reading is therefore limited: the registry reports cohort-level safety counts, but not a single inferential result that resolves the primary safety question.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how an early-phase safety study can generate descriptive evidence without yielding a single comparative estimate. The registry records randomized, placebo-controlled allocation and masking, but the posted primary outcome spans several event categories and is not reduced to one comparison. That distinction matters: a reader can describe observed counts without assuming that a formal treatment effect was estimated.

The cohort structure is also important. Safety is reported across pooled placebo, multiple VIS649 cohorts, and groups labeled as including vaccine. The group sizes vary, and the registry does not state how the cohorts should be combined for a treatment contrast. A single summary across these groups could obscure differences in dose or cohort context; the record does not provide the information needed to judge such a pooling strategy.

The study demonstrates why outcome type and estimand matter. An event count, the number of affected participants, and a comparison of risks are not interchangeable summaries. The registry reports affected-participant counts for other adverse events and zero serious-event counts, but does not report comparative uncertainty estimates for the primary outcome. Without those estimates and a documented analysis strategy, the results support description rather than precise comparative inference.

It also illustrates the importance of distinguishing design assumptions from trial results. The record’s sample-size description is a planning illustration, not a justification or a measure of observed power. Interpreting the study requires keeping that planning framework separate from the actual safety observations and recognizing the limits created by unreported analysis and missing-data details.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry does not provide a single primary-outcome comparison, an effect estimate, or uncertainty interval. It lists adverse-event information by group, but does not report an event-level account, a drug-relatedness breakdown, or the method used to handle recurrent events. As a result, the descriptive counts cannot be translated into a comparative estimate from the registry record.

Group composition and dose assignment are not fully described alongside the posted safety results. The record includes cohort labels and groups identified as Cohort 5 + Vaccine, but does not explain how those groups relate to the planned cohort structure or how they should be combined. The brief summary’s planned enrollment of up to 45 subjects also differs from the reported enrollment of 51; the registry does not explain this difference.

The record gives no detailed account of randomization sequence generation, allocation concealment, who was masked, or how masking was maintained. It uses both quadruple-masking and double-blind descriptions. It does not report a statistical analysis plan, multiplicity procedures, missing-data methods, follow-up completeness, interim analyses, or sample-size justification. These details are not reported in the registry record.

The stated population is healthy subjects, which limits interpretation for populations with the listed conditions. Numerical pharmacokinetic and pharmacodynamic results are not included in the registry record for this analysis. Finally, absence of reported serious events in the posted groups does not establish absence of risk, particularly when the record does not provide uncertainty intervals or a comprehensive event-level presentation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: First in Human Study to Assess Safety of VIS649 in Healthy Subjects — NCT03719443.
• Registry record last updated 2026-05-01; status last verified 2026-04.
• Results first posted 2025-03-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record identifies NCT03719443 as a completed Phase 1, randomized, placebo-controlled, parallel-group, single-ascending-dose study of VIS649 in healthy subjects. It reports quadruple masking, while the brief summary also describes the study as double-blind. Recorded enrollment was 51; the brief summary describes planned enrollment of up to 45 subjects. The study start was 2018-10-09 and primary completion was 2019-08-10.

The intervention was a single intravenous VIS649 dose, with a single intravenous placebo comparator. The primary outcome was an overall summary of treatment-emergent adverse events from baseline to day 112. The posted safety results list no serious adverse events or deaths in the groups and give other adverse-event affected-participant counts by group. No primary-outcome analyses or single comparative estimate are reported.