A Study to Evaluate the Safety, PK, PD, Immunogenicity of N-Rephasin® SAL200 in Healthy Male Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety, PK, PD, Immunogenicity of N-Rephasin® SAL200 in Healthy Male Volunteers (NCT03446053), a randomized phase 1 study. The primary outcome is Safety and Tolerability Evaluation.

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, double-blind, placebo-controlled, parallel-group study with quadruple masking. Its official title describes a multiple-dosing, dose-escalating study; the brief summary says that single and multiple ascending doses were evaluated after continuous intravenous infusion over 60 minutes. The population was healthy male volunteers. The registry lists an enrollment of 33 and a status of completed.

The registry arm description says that forty subjects would be randomly assigned to receive N-Rephasin® SAL200 or placebo. It describes a single dose of 6 mg/kg followed by multiple ascending doses, but the dose sequence in that text is truncated. The adverse-event listings separately identify a single-dose placebo group, a single-dose N-Rephasin® SAL200 (6mg/kg) group, a multiple-dose placebo group, and multiple-dose N-Rephasin® SAL200 groups at 1.5 mg/kg, 3 mg/kg and 4.5 mg/kg. The record does not explain the relationship between the planned arm description and these listed groups, so the dose progression should not be reconstructed beyond what is explicitly listed.

The study began on 2018-02-07, had a primary completion date of 2019-02-07, and is recorded as completed. The sponsor was Intron Biotechnology, Inc. The registry record does not report the randomization sequence, allocation concealment procedures, masking roles, or the details of dose-escalation decisions. Nor does it report whether all enrolled participants completed follow-up or were included in each adverse-event group. The recorded enrollment and the planned assignment described in the arm text are different figures; the record does not explain that difference. These details matter when interpreting how closely the completed study followed its planned 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: 59 subjects were screened and 33 subjects met inclusion criteria and were randomized to treatment.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability Evaluation, measured over Up to 50D (±2D).

The primary endpoint is titled “Safety and Tolerability Evaluation.” It is measured as a count of participants, and its description specifies monitoring for adverse events. The stated timeframe is up to 50D (±2D). This endpoint is intended to describe how many participants experience adverse events during follow-up, rather than to measure a clinical benefit in patients with an infection.

Participant counts are useful in early-phase studies because safety evaluation requires identifying whether adverse events occurred and in which dose groups. Counts can make the observed experience of small groups visible without implying that the study was designed to estimate a precise risk difference. They do not, on their own, account for how long each participant was observed, the severity of every event, whether events recurred, or whether an investigator considered an event related to the intervention. Those details require specific definitions and results.

The registry record reports eight outcome measures, but the primary outcome is not reduced to a single comparison because it has several categories or time points. It does not report a single primary endpoint estimate, a confidence interval, or an inferential test for a comparison between SAL200 and placebo. Thus, the endpoint description indicates what was monitored, while the available counts provide a limited view of recorded adverse events rather than a complete statistical analysis of safety and tolerability.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are useful only when they match the design, endpoint, and data actually reported. For this study, the primary endpoint is a count of participants monitored for adverse events. The posted record gives group-specific event counts, but reports no statistical analyses. Consequently, statistical concepts can help explain the information without implying that a particular model or test was used in the study.

What does a participant count describe?

A participant count records how many people in a group had the outcome, according to the outcome definition. It differs from a continuous measure, such as a laboratory value, because the result is a category for each person: the event was recorded or it was not. For adverse-event monitoring, a count is an understandable descriptive summary. Interpretation still depends on the definition of an event, the observation period, completeness of follow-up, and whether repeat events are counted once per person or separately. The primary outcome description specifies monitoring, but the registry record does not report all these operational details.

Counts should be considered alongside the number of participants at risk. Groups of different sizes can produce different counts even when their underlying event patterns are similar. The posted adverse-event information includes both the number at risk and the number affected for the listed groups, which makes the group sizes explicit. It does not report uncertainty intervals around the counts or a model-based comparison. Without those, the counts alone do not quantify how precisely the underlying event experience has been estimated.

Why are small-group comparisons uncertain?

In general, estimates from small groups can vary substantially if the experience of only one or a few participants changes. A zero count means no affected participant was recorded in that group during the reported observation; it does not mean the true chance of an event is zero. Confidence intervals are one way to express uncertainty around an estimate. A confidence interval gives a range of values compatible with the observed data under the method's assumptions. No confidence intervals are reported for these adverse-event results.

Comparisons also need to account for how participants were assigned, which groups are being compared, and whether the analysis follows the randomized assignment. Randomization is recorded, but the registry record does not give the sequence-generation or concealment procedures, analysis populations, or a prespecified comparison for the primary outcome. The design label alone is not enough to establish how a statistical analysis was carried out.

What do masking and parallel groups contribute?

In general, masking can reduce the influence of expectations on care, event reporting, and assessment. A parallel-group design assigns participants to groups that are followed as separate groups. The registry identifies quadruple masking and a parallel model, but does not define the masked roles or describe any unmasking procedures. Therefore, these design features can be noted, but their implementation cannot be assessed from the registry record.

A placebo comparator can help distinguish events observed during study participation from events that would also occur without the active intervention. That distinction is not automatic: event definitions, background health, observation, and chance all affect the counts. The registry record lists placebo as saline, but does not report event attribution methods or a statistical comparison with placebo. The counts should therefore be presented descriptively rather than interpreted as a causal contrast.

Why might a count model need special care?

In general, count data can be analyzed using methods suited to the way observations arise. If the outcome is whether each participant experienced an event, a binary-outcome method may be suitable; if the endpoint is the total number of repeated events, a count model may be considered. These are not interchangeable endpoints. Repeated events from the same participant may be related, and the amount of time under observation may differ. Over-dispersion means that count variability is greater than a model expects; if present, it can make standard errors and uncertainty estimates too small unless addressed. The registry record does not state that a count model, a binary model, or any other specific method was used.

For the posted safety information, the reported measure is a count of participants affected, not a total count of all event episodes. The record does not give the event-level detail needed to characterize recurrences, time to first event, or exposure-adjusted rates. Those quantities should not be inferred from the participant counts.

How should planning illustrations be read?

In general, a sample-size calculation depends on a target effect, a significance level, allocation, variability or event assumptions, and the chosen statistical method. A planning illustration based on a stated fraction of an observed effect describes a hypothetical design under assumptions; it does not recover the original protocol's rationale. The calculation assumptions identified for the illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For non-time-to-event outcomes, the illustration is expressed as participants per arm; for time-to-event outcomes, it is expressed as the total number of events. These are planning conventions, not observed power and not evidence that the trial was designed with those exact assumptions.

The registry record does not report its own sample-size justification, an interim-analysis plan, or a statistical analysis plan. It also does not provide a single analyzed comparison for the primary endpoint. In general, the absence of a reported inferential method means that readers cannot verify assumptions, multiplicity handling, or the construction of uncertainty estimates. The appropriate approach is to distinguish the recorded counts and design features from analyses that are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures and reports no statistical analyses. The primary outcome is not reduced to a single comparison because it has several categories or time points. This means the available record does not identify one reported primary estimate against which other results can be interpreted, nor does it describe an inferential testing strategy across multiple outcomes or dose groups.

In general, testing many outcomes, time points, or group comparisons can increase the chance of finding an apparently notable result by chance. Statistical plans may address this issue by prespecifying a primary comparison, adjusting inference, or treating secondary analyses as descriptive. The registry record does not report whether any such strategy was planned or used. It would therefore be inappropriate to assume that multiplicity was controlled in a particular way.

The registry record also does not report the analysis populations, missing-data methods, or participant disposition by outcome. It is not possible to determine from the posted details whether all randomized participants were analyzed, how missing observations were handled, or whether follow-up differed across groups. In general, missing outcome information can affect interpretation if the chance of missingness is related to participant characteristics or adverse events. No particular missing-data mechanism can be inferred.

The enrollment is recorded as 33, while the arm description states that forty subjects would be randomly assigned. The record does not explain this difference or provide enough disposition detail to reconcile planned assignment with the listed group counts. These reporting gaps limit the assessment of analysis completeness and the interpretation of cross-group comparisons.

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 listings report 0 affected participants in every group and 0 deaths in every group. The numbers at risk are 2 for single-dose placebo, 6 for single-dose N-Rephasin® SAL200 (6mg/kg), and 6 in each of the multiple-dose groups: placebo, 1.5 mg/kg, 3 mg/kg and 4.5 mg/kg. These are the serious-event counts recorded in the registry.

The other adverse-event counts affected are 1 for single-dose placebo, 6 for single-dose N-Rephasin® SAL200 (6mg/kg), 1 for multiple-dose placebo, 3 for multiple-dose N-Rephasin® SAL200 (1.5 mg/kg), 1 for multiple-dose N-Rephasin® SAL200 (3 mg/kg), and 3 for multiple-dose N-Rephasin® SAL200 (4.5 mg/kg). These figures describe participants affected, not the total number of individual event episodes. The registry record does not report event severity beyond the serious-event classification, investigator attribution, or the timing and recurrence of other adverse events.

In general, zero observed serious events in small groups should not be interpreted as evidence that serious events cannot occur. Nor do differences in descriptive counts establish that a dose caused or prevented an event. The counts are useful for understanding what was recorded during the study, but they do not replace a complete safety analysis with defined event categories, follow-up completeness, and uncertainty estimates.

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

The posted results document participant counts for adverse events in the listed single-dose and multiple-dose groups. Serious adverse events affected 0 participants in each group, and the record lists 0 deaths in each group. Other adverse events were recorded in each group, with the affected-participant counts varying across the groups. These observations describe the study participants during the reported monitoring period; they do not, by themselves, estimate a causal difference between SAL200 and placebo.

The study was a randomized, quadruple-masked phase 1 trial in healthy male volunteers. Its stated objectives included safety, pharmacokinetics, pharmacodynamics and immunogenicity. Those design and objective details give context, but the available safety counts do not answer every objective. In particular, they do not provide a pharmacokinetic profile, a pharmacodynamic estimate, or an immunogenicity result. Although the registry record lists eight outcome measures, it does not report a statistical analysis for them.

In general, a trial result is more informative when it includes an effect estimate, uncertainty interval, clear analysis population, outcome definitions, and a prespecified analysis method. Here, the registry record reports no analyses and does not provide a formal comparison for the primary safety endpoint. The absence of a reported comparison should not be recast as evidence of equivalence or as a finding of no difference. Similarly, the adverse-event counts should not be interpreted as proof that the intervention is safe or unsafe.

The enrollment of 33 and the planned assignment of forty subjects in the arm description are both recorded, but the record does not explain their relationship. The listed adverse-event group counts are small, and the record does not give the analysis populations or missing-data handling. Those limitations leave uncertainty about the completeness and precision of the posted safety results.

The appropriate conclusion is restricted to the record: it describes adverse-event counts by listed group, with no serious adverse events or deaths recorded in those groups, and no formal statistical analysis reported. Broader claims about comparative safety, dose response, or clinical benefit are not established by these counts.

13. Why This Trial Matters Statistically

Early-phase studies have a different statistical emphasis from trials designed to establish a clinical effect in a patient population. This study's stated purpose was to assess safety, pharmacokinetics, pharmacodynamics and immunogenicity in healthy male volunteers after single and multiple ascending doses. Its primary outcome focused on adverse-event monitoring. Interpreting that work requires keeping descriptive safety observations distinct from evidence about treatment benefit.

Several features make statistical reporting especially important in a dose-escalation study. Event counts are grouped by dose and by single-dose or multiple-dose study, while the groups are small. A reader needs clear definitions, group denominators, follow-up information, and an explanation of which comparisons were planned. The registry reports counts at risk and affected for the listed groups, but does not provide a statistical analysis, a formal dose comparison, or the analysis plan. That gap shows why count data should not be treated as self-interpreting.

The record also illustrates the importance of distinguishing a planned enrollment statement from the enrollment recorded for a completed study. The arm description refers to forty subjects, while the enrollment field records 33. Without disposition information, the reasons for that difference and its implications for analysis cannot be established.

More generally, transparent reporting should make clear how randomization, masking, missing data, multiplicity, and sample-size planning were handled. The registry identifies randomization, quadruple masking, and a parallel design, but does not report important operational details or the trial's sample-size justification. These omissions matter statistically because they limit evaluation of bias, precision, and reproducibility. The record remains useful as a description of design and observed counts, while also demonstrating why complete analytic reporting is necessary for stronger interpretation.

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 record leaves important details unavailable for interpreting this specific study. It reports enrollment of 33, while the arm description says forty subjects would be randomly assigned; it does not explain the difference or give participant disposition by group. The adverse-event listings give the numbers at risk and affected, but do not establish whether those counts represent all randomized participants or a particular analysis population.

The dose information is not fully consistent in its level of detail across the record. The arm description gives a truncated multiple-dose sequence, while the adverse-event groups list multiple-dose doses of 1.5 mg/kg, 3 mg/kg and 4.5 mg/kg. The record does not explain the relationship between the descriptions, so the regimen should not be reconstructed beyond the listed text. It also does not report actual infusion completion, exposure duration by participant, or reasons for dose changes.

For adverse events, the record does not report event definitions, severity grading for non-serious events, investigator attribution, timing, recurrence, or missing safety observations. It provides no confidence intervals or formal statistical comparisons. The record does not report a statistical analysis plan, sample-size justification, interim analyses, multiplicity approach, or missing-data method. It also does not define the roles covered by quadruple masking or describe the procedures used to maintain masking.

These limitations mean that the counts can be described, but precision, causal attribution, dose-response patterns, and completeness of analysis cannot be assessed from the registry record. The study's stated objectives included pharmacokinetics, pharmacodynamics and immunogenicity, but their detailed outcome results are not reported in the record details used for this interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety, PK, PD, Immunogenicity of N-Rephasin® SAL200 in Healthy Male Volunteers — NCT03446053.
• Registry record last updated 2021-11-03; status last verified 2021-09.
• Results first posted 2021-10-08.
• 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

NCT03446053 is a completed, randomized, quadruple-masked, parallel-group phase 1 study sponsored by Intron Biotechnology, Inc. It evaluated N-Rephasin® SAL200 and placebo in healthy male volunteers, with continuous intravenous infusion over 60 minutes. The registry records enrollment of 33 and describes an intended assignment of forty subjects in the arm text.

The primary outcome was a participant count for safety and tolerability evaluation based on adverse-event monitoring through up to 50D (±2D). The adverse-event listings report 0 serious adverse events and 0 deaths in each group, alongside other adverse-event counts that vary across the listed groups. The record reports eight outcome measures and no statistical analyses. It does not report the analysis populations, missing-data approach, sample-size justification, interim analyses, or statistical analysis plan. The posted counts are descriptive and do not establish a formal comparison of SAL200 with placebo.