sPIF CLINICAL STUDY PROTOCOL IN AUTOIMMUNE HEPATITIS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for sPIF CLINICAL STUDY PROTOCOL IN AUTOIMMUNE HEPATITIS (NCT02239562), a randomized phase 1 study. The primary outcome is Safety/Tolerability Measured by Clinical Laboratory Tests, Metabolics, Cytokines, Anti-PIF Antibody, Periodic Physical Examination, Including Vital Signs Measurements and 12-lead ECG.

2. Clinical Question

This is an early-phase safety study, not a registry-reported test of clinical benefit. Its stated focus was to observe safety, tolerability, and circulating blood levels of sPIF in the study population. The listed dosing groups distinguish single-dose from multiple-dose exposure and include several dose levels. Those distinctions are important when interpreting the safety entries: the results are recorded separately by group, rather than as a single pooled comparison of sPIF with placebo. The registry record does not describe a primary efficacy question or report an efficacy result.

3. Trial Design

The registry identifies this as a Phase 1, randomized, double-blind, placebo-controlled study with quadruple masking and a parallel-group model. Enrollment was 36. The study status is completed; the recorded start date is 2014-11-14 and the primary completion date is 2016-04-25. The sponsor is Christopher O'Brien, MD.

The study included single ascending dose (SAD) and multiple ascending dose (MAD) groups. SAD groups received one subcutaneous dose on Day 1 at 0.1 mg/kg, 0.5 mg/kg, or 1.0 mg/kg. MAD groups received one subcutaneous dose daily for 5 consecutive days, Days 1 to 5, at the corresponding dose levels. The registry describes patients with normal and abnormal liver function tests in the dose-group descriptions. Within those descriptions, randomization was in a 2:1 ratio (active drug:placebo).

Assessments varied by dosing schedule. For SAD, the registry lists adverse events and concomitant medications on Days 1, 2, 3, 5, and 8, with specified clinical examinations, laboratory tests, pharmacokinetic sampling, and other assessments on selected study days. For MAD, it lists adverse-event and medication monitoring through Day 29, with other assessments at the time points specified in the registry description. The primary outcome timeframe is 29 Day.

The registry record does not report the allocation sequence method, concealment procedures, how masking was maintained, or the rationale for the planned enrollment. It also does not report details of dose-escalation decisions or the criteria used to move between dose groups. These details should not be inferred from the study’s title or its ascending-dose structure.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients participating in each arm were assessed for adverse events by symptoms, physical examination and laboratory studies.

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.

Population: Females only

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety/Tolerability Measured by Clinical Laboratory Tests, Metabolics, Cytokines, Anti-PIF Antibody, Periodic Physical Examination, Including Vital Signs Measurements and 12-lead ECG, measured over 29 Day.

The primary endpoint is described as safety and tolerability measured through clinical laboratory tests, metabolic measures, cytokines, anti-PIF antibody assessment, periodic physical examination, vital signs, and 12-lead ECG. The registry lists the outcome unit as participants and the measure as a count of participants. The assessment timeframe is 29 Day. The registry also describes safety monitoring through adverse events and concomitant medications, with different scheduled assessments for the single and multiple ascending dose groups.

In general, a broad safety endpoint is used in an early-phase study to identify and characterize possible tolerability concerns across clinical observations and laboratory measures. These different assessments capture different types of information; a participant count does not by itself describe the nature, timing, severity, or clinical importance of an event. A count also does not establish whether an observed event was caused by the study drug.

The registry record does not report primary-outcome results by category or provide a single comparative estimate for sPIF versus placebo. It therefore does not support a numerical estimate of the primary endpoint’s treatment contrast or its precision. The listed adverse-event entries provide a limited view of reported event counts, but they are not a substitute for the full set of primary safety assessments.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies randomization, quadruple masking, a placebo control, and a parallel-group model. These design features describe how treatment groups were intended to be compared, but the record does not report the statistical analysis plan. In particular, it does not state which statistical tests or models were planned for the primary safety endpoint, how repeated measurements were to be handled, or whether analyses were adjusted for any baseline factors.

What does randomization contribute?

In general, randomization assigns participants to study groups by chance. When implemented well, it helps reduce systematic differences between groups at the point of assignment. It does not guarantee that groups will be similar on every characteristic, especially in a small early-phase study. The registry record does not describe the randomization sequence or concealment method, so those procedural details are not reported in the registry record.

How should masking be understood?

In general, masking is intended to limit the influence of treatment knowledge on participants, clinicians, or those assessing outcomes. The registry labels the study quadruple-masked, but does not specify which roles were masked or how masking was maintained. The label should therefore be reported as a design feature, not treated as evidence about the success of masking.

What do the adverse-event counts show?

The posted safety entries are counts of participants with events within each listed group. Counts are useful for describing what was recorded, but do not alone provide a comparative effect estimate or quantify uncertainty. For example, a zero count indicates no event was recorded in that group in the registry entry; it does not demonstrate that the underlying event risk is zero. A comparison would ordinarily require an explicit effect estimate and a measure of its precision. Neither is reported for the primary outcome.

In general, confidence intervals convey the range of effect values compatible with the data under a specified statistical method. Their width reflects precision: wider intervals indicate greater uncertainty. The registry record does not report confidence intervals for the primary outcome or the adverse-event counts, so the precision of any between-group contrast cannot be evaluated from the posted results.

Why might event counts be difficult to compare?

General statistical considerations matter when outcomes are uncommon and groups are small. Counts can be sparse, making estimates unstable; methods that rely on large-sample approximations may perform poorly in such settings. The registry record does not report the analysis method used for event comparisons, so no particular method can be attributed to this study. The record also does not provide enough outcome detail to assess event timing, recurrence, severity, or treatment relationship.

The primary outcome combines multiple kinds of safety information, including laboratory measures, physical examinations, vital signs, ECG, antibodies, cytokines, and metabolic tests. These measures have different scales and meanings. In general, they may require different summaries or analyses, and a count of participants does not describe the full distribution of continuous laboratory or physiological measurements. The registry record does not report how these different components were combined, prioritized, or analyzed.

What can be said about sample-size planning?

The registry record does not report the trial’s own sample-size justification or statistical power calculation. Any planning illustrations based on an observed effect are not evidence of observed power and should not be read as the study’s original design rationale. The described illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such assumptions are planning conventions, not trial results. The registry does not report an observed primary-outcome effect from which readers could assess clinical or statistical importance.

Finally, the record lists no analyses for the outcomes. No inferential result, model specification, handling of repeated observations, or adjustment strategy is reported in the registry record. The appropriate statistical reading is therefore descriptive: report the recorded group-level safety counts, distinguish them from the broad primary endpoint, and avoid inferring comparative effects that the record does not estimate.

10. Multiplicity, Missing Data and Analysis Populations

The primary safety outcome includes several kinds of assessment, and the registry also lists a secondary outcome concerning participants with anti-sPIF antibodies and drug interactions. The registry record does not report how many comparisons or outcome components were included in a prespecified statistical plan, whether any outcome hierarchy was used, or whether multiplicity was addressed. Multiplicity arises when several outcomes or comparisons are examined: the chance of at least one apparently notable result can increase when many tests are considered. This general issue cannot be quantified for this study from the registry record.

The posted record does not report an analysis of the primary outcome, and it does not report inferential analyses. It also does not describe analysis populations, such as whether outcomes were analyzed according to randomized assignment or based on treatment received. The registry record does not state how participants who discontinued, missed assessments, or had incomplete measurements were handled. Missing-data methods and the amount or pattern of missing data are not reported in the registry record.

These omissions limit interpretation. Without a defined analysis population and information about completeness, it is not possible to determine whether the posted counts include all randomized participants or only participants with available assessments. Without a reported multiplicity approach, isolated findings across several safety measures would need cautious interpretation. These are general methodological concerns; the record does not establish that missing data or multiplicity affected the results.

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 registry records serious adverse events, other adverse events, and deaths separately for each listed group. Each group has six participants at risk in the registry entry. Serious adverse events are recorded as zero in all listed groups, and deaths are also recorded as zero in all listed groups. For other adverse events, the Single Ascending Dose 0.1 group has two affected participants; the remaining listed groups have zero.

These entries are counts, not a complete clinical account of the events. The registry record does not describe the two other adverse events, their severity, onset, duration, treatment relationship, or outcomes. It also does not report comparative statistical estimates or confidence intervals for these safety counts. In general, zero recorded events in a study group does not establish zero risk; rare events may not appear during a study of limited size or observation.

Serious adverse events and other adverse events are different reporting categories, so the two entries in the SAD 0.1 group should not be interpreted as serious events. The registry record lists no serious-event terms. The counts describe what is recorded in the registry, not a complete assessment of every safety measure named in the primary endpoint.

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

The registry record describes a completed Phase 1 randomized study of sPIF in female patients with autoimmune hepatitis. It reports separate SAD and MAD dose groups, placebo comparators, and adverse-event counts. Those counts show no serious adverse events or deaths recorded in the listed groups, and two participants with other adverse events in the Single Ascending Dose 0.1 group. They do not provide a comprehensive account of the full safety endpoint.

The result does not establish that sPIF is safe in all circumstances, that it is free from risk, or that it changes the course of autoimmune hepatitis. The record does not report a comparative primary-outcome analysis, an efficacy outcome, or a quantified treatment effect. It also does not report results for the laboratory, cytokine, antibody, physical examination, vital-sign, or ECG components listed in the primary endpoint. No conclusion about the size or precision of a treatment effect can be drawn from the posted event counts alone.

In general, early-phase studies are designed to collect initial information about exposure and tolerability, and their findings need to be interpreted within the population, doses, and observation schedule studied. That general context does not fill gaps in the registry record: the study’s statistical plan, missing-data handling, and primary-outcome analysis are not reported. Nor can the posted counts establish whether an event was caused by treatment.

The most defensible reading is descriptive. The registry provides group-specific adverse-event entries and the stated scope of safety monitoring, but no reported inferential result for the primary outcome. Any stronger claim about comparative safety, pharmacokinetics, or clinical benefit would go beyond what the registry record reports.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of how early-phase trial design and outcome reporting differ from a definitive comparative-effectiveness analysis. It combines a placebo-controlled randomized design with dose groups for single and repeated exposure. That structure can organize safety observations by dosing schedule and dose, while the registry entries make clear that the posted adverse-event data are counts within groups rather than a single pooled treatment contrast.

The record also illustrates why endpoint labels and numerical results should be distinguished. The primary endpoint is broad, covering clinical, laboratory, immunological, and physiological assessments, but the registry does not report the corresponding analyzed results. The adverse-event counts are available as a narrower descriptive component. They should not be treated as if they summarize every primary safety measure or answer a comparative question with known precision.

Small group-level counts call for careful interpretation. In general, observing no events does not rule out uncommon events, and a count without an uncertainty estimate does not show how precisely groups differ. This is particularly relevant when a study’s stated purpose is safety and tolerability. The record’s lack of reported analyses also highlights the role of transparent statistical reporting: the analysis population, methods, uncertainty, and handling of missing information are needed to understand how results support conclusions.

The trial matters statistically because it makes visible both the value and limits of registry data. Design information and event counts can support a clear description of what was planned and recorded. They cannot replace an analysis of the full endpoint, nor can they support claims that the registry does not report.

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 offers limited detail for interpreting the reported safety findings. Although it describes the study as randomized and quadruple-masked, the randomization procedure, allocation concealment, masking roles, and maintenance of masking are not reported in the registry record. Dose-escalation criteria and the protocol’s statistical plan are also not reported.

The primary endpoint covers a range of safety measures, but the registry record does not report their results by group or provide a comparative analysis. The adverse-event entries do not describe individual event terms, severity, timing, duration, resolution, or attribution. The record lists a secondary outcome concerning anti-sPIF antibodies and drug interactions, but its results are not reported.

The registry record does not report the analysis populations, the number of participants with complete data for each assessment, the handling of missing observations, or reasons for any missingness. It also does not report a sample-size justification, interim analyses, multiplicity procedures, effect estimates, p-values, or confidence intervals. These gaps prevent assessment of statistical precision and make it impossible to determine how the posted counts relate to all planned safety assessments.

The study’s enrollment and group-level entries should be understood as registry information, not as a basis for claims about uncommon harms or broader patient populations. The recorded results apply to the listed study groups and observation schedule; extrapolation beyond them is not supported by the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: sPIF CLINICAL STUDY PROTOCOL IN AUTOIMMUNE HEPATITIS — NCT02239562.
• Registry record last updated 2019-11-20; status last verified 2019-10.
• Results first posted 2019-11-20.
• 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 describes NCT02239562, titled “sPIF CLINICAL STUDY PROTOCOL IN AUTOIMMUNE HEPATITIS,” as a completed Phase 1 randomized, double-blind, placebo-controlled study with quadruple masking and a parallel-group model. Enrollment was 36. The study evaluated single and multiple ascending subcutaneous doses of sPIF in female patients with autoimmune hepatitis, with placebo comparators.

The primary outcome concerned safety and tolerability over 29 Day and included clinical, laboratory, immunological, examination, vital-sign, and ECG assessments. The registry reports adverse-event counts by dose group: no serious adverse events or deaths are recorded, and two participants with other adverse events are recorded in the Single Ascending Dose 0.1 group. No primary-outcome analysis or inferential results are reported in the registry record.