A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection (NCT04585789), a non-randomized phase 2 study. The primary outcome is Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40.

2. Clinical Question

3. Trial Design

The registry describes a Phase 2, open-label, parallel-group, multicenter study in chronic hepatitis B virus infection. Its status is completed. The recorded start date is 2021-03-11, and the primary completion date is 2023-02-08. Enrollment is listed as 24.

There is an important inconsistency in how allocation is described. The official title calls the study randomized, but the allocation field says non-randomized. The record therefore does not support treating the panels as randomized arms for a causal comparison. It also explicitly cautions that the arms are not a like-for-like control comparison. How participants were assigned or enrolled into each panel, and whether any allocation procedure changed during the study, is not reported in the registry record.

The primary endpoint is defined for Panels 1 and 2 and measures change in the percentage of HBsAg-positive hepatocytes from baseline to Week 40. The listed treatment descriptions include JNJ-73763989 administered by subcutaneous injection every 4 weeks, with the last injection at Week 44, alongside daily nucleos(t)ide analog treatment up to 48 weeks. The listed nucleos(t)ide analog options are entecavir, tenofovir disoproxil, and tenofovir alafenamide. The Panel 2 description also mentions optional PegIFN-alpha-2a after Week 40, but its duration is incomplete in the registry record.

The record lists Panels 1, 2, and 3 for several secondary outcomes, but does not give complete treatment descriptions for all panels. It lists 41 outcome measures and no analysis entries. The sample-size justification, details of any interim analyses, and a full statistical analysis plan are not reported in the registry record.

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: As per protocol amendment (PA) 5 (dated 01 October 2021), all participants stopped JNJ-56136379 (JNJ-6379) treatment and continued treatment with JNJ-73763989 (JNJ-3989) plus nucleos(t)ide analog (NA; ETV, TD, or TAF) plus optional pegylated interferon alpha-2a (PegIFN-alpha2a). The study consisted of 3 phases: screening phase, open-label (OL) intervention phase and follow-up (FU) phase.

OL Phase: Week 1 to Week 48

FU Phase: Week 48 to Week 96

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for Panels 1 and 2 alone.

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 Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40, measured over Baseline, Week 40.

The primary endpoint is the absolute change from baseline to Week 40 in the percentage of hepatocytes that are positive for hepatitis B surface antigen (HBsAg), assessed using liver biopsy. It is defined for Panels 1 and 2. The registry describes the result as a mean and specifies an 80% confidence interval, but the estimate and interval values are not reported in the registry record.

This endpoint measures a tissue-level marker rather than a symptom or a clinical event. In general, measuring the proportion of HBsAg-positive hepatocytes can describe how the marker changes in liver tissue over the treatment period. A change from baseline accounts for each participant’s starting measurement in the endpoint definition, while the group mean describes the average change across the analyzed participants. This does not by itself establish why a change occurred or whether it translates into a clinical benefit.

Liver biopsy is the specified measurement source at baseline and Week 40. As a general statistical consideration, a change endpoint depends on obtaining comparable measurements at both time points and on how participants without usable measurements are handled. Those measurement and missing-data procedures are not reported in the registry record. Because no primary estimate, confidence interval, or analysis result is listed, the magnitude, direction, and precision of the observed change cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how measurements are summarized, compared, and interpreted. The registry record identifies the primary outcome as a mean change and specifies an 80% confidence interval. It does not report the calculation method for that interval, the model used for the endpoint, or an inferential test. These details are not reported in the registry record.

What does a mean change describe?

In general, a mean change is the average of participants’ changes between the defined starting and follow-up measurements. For this endpoint, the starting measurement is baseline and the follow-up is Week 40. A mean can give a concise account of the group’s average trajectory, but it does not show how much individual participants differed from that average. A mean also does not tell readers whether the result was driven by a small number of unusually large changes. The registry record does not provide the individual-level data or a measure of spread for the primary endpoint.

How should the confidence interval be read?

In general, a confidence interval expresses uncertainty associated with an estimate under the assumptions of the analysis method. A narrower interval indicates greater precision than a wider interval for the same kind of estimate. Its interpretation depends on the method and assumptions used. The primary endpoint specifies an 80% confidence interval, but the interval limits and its construction are not reported in the registry record. A confidence interval is not a measure of clinical importance, and it does not establish that a treatment caused the estimated change.

Why does allocation matter?

In general, random allocation can help balance measured and unmeasured participant characteristics across comparison groups, while non-random allocation may leave groups different before treatment begins. This affects how confidently a difference between groups can be interpreted as a treatment effect. In this study, the title describes randomization but the allocation field says non-randomized. The record also warns that arms are not a like-for-like control comparison. Consequently, a between-panel contrast should not be read as a randomized treatment effect based on the information in the registry record.

Open-label means the study is not masked, as indicated by the masking field. In general, knowledge of treatment assignment can influence participant behavior, clinical management, or outcome assessment, depending on how outcomes are collected. A biopsy-based laboratory marker may involve less subjective judgment than a self-reported outcome, but the registry record does not describe blinding of laboratory staff, biopsy reading procedures, or safeguards against assessment bias. No conclusion about those procedures can be drawn.

What do the planning assumptions mean?

The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. In general, such illustrations explore how a hypothetical future study might be sized under chosen assumptions. They are not evidence that the completed study had a particular probability of detecting an effect, and they are not observed power. The actual sample-size justification and planning assumptions used for the trial are not reported in the registry record. The observed effect needed to interpret the planning illustrations is also not reported in the registry record.

General statistical caution applies when outcomes are counts, proportions, or repeated measurements. Their distribution and variability may differ from assumptions used in simple models. Over-dispersion, for example, occurs when count variability exceeds what a model expects; in general, ignoring it can make uncertainty appear too small. The record does not state that over-dispersion was present or that a particular count model was used. It is not possible to infer the selected model from the endpoint descriptions alone.

The registry lists 41 outcome measures but no analysis entries. It does not report model covariates, handling of baseline values, treatment of repeated measurements, interval construction, sensitivity analyses, or whether any planned analyses were changed. Those methods are not reported in the registry record. Without those details and the numerical results, readers cannot independently assess the assumptions, reproduce the analysis, or judge the robustness of the primary estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 41 outcome measures, including the primary liver-cell endpoint and multiple secondary virologic and intrahepatic measures. When many outcomes are evaluated, the chance of at least one apparently notable finding can increase if no multiplicity strategy is used. In general, multiplicity procedures may control the overall error rate, prioritize a hierarchy of outcomes, or otherwise distinguish confirmatory from exploratory analyses. The registry record does not report a multiplicity adjustment, testing hierarchy, or analysis plan for the outcomes.

The record lists no analysis entries and gives no numerical results for the primary or secondary outcomes. Whether the outcomes were analyzed as planned, whether any outcomes were treated as exploratory, and how multiple comparisons were handled are not reported in the registry record. Without that information, no conclusion can be made about the statistical status of any individual outcome finding.

The primary population description refers to an intent-to-treat population that included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose, and says participants were analyzed according to the intervention to which they were assigned or enrolled. The record’s wording reflects both assigned and enrolled participants, alongside the inconsistency between its randomized title and non-randomized allocation field. The number analyzed for the primary endpoint and the number with usable baseline and Week 40 biopsy measurements are not reported in the registry record.

In general, missing outcome measurements can affect both the estimated change and its precision. Interpretation depends on how many measurements were unavailable, why they were unavailable, and how the analysis handled them. The registry record does not report missing-data counts, reasons for missing biopsies, imputation procedures, or sensitivity analyses. It also does not report whether the analysis population differed from the enrolled population. These omissions limit assessment of the representativeness and robustness of the endpoint estimate.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastroenteritis (10.0%).

The registry separates safety listings into open-label and follow-up phases, with groups labeled by panel. In the open-label phase, Panel 1 lists 10 participants at risk and 1 affected by a serious adverse event; Panel 2 lists 10 at risk and 0 affected; Panel 3 lists 4 at risk and 0 affected. In the follow-up phase, Panel 1 lists 10 at risk and 0 affected, Panel 2 lists 10 at risk and 0 affected, and Panel 3 lists 4 at risk and 0 affected.

Deaths are listed as 0 for each of these groups. The leading serious-event term listed in the registry is gastroenteritis, at 10.0%. The record does not identify that term’s panel attribution in the listed summary, so it should not be assigned to a specific panel based on this information alone.

These are descriptive safety counts, not comparative estimates of risk. The open-label and follow-up listings are separate reporting periods, and the record does not explain whether the same participants contribute to both periods. The counts should not be added across phases to create a unique-participant total. The small group sizes and absence of a like-for-like control comparison also limit interpretation of differences between panels. The registry record does not provide event-level timing, severity breakdowns, or a causal assessment for the listed serious events.

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

The study’s stated purpose was to assess changes in intrahepatic HBsAg between baseline and an on-treatment liver biopsy in response to JNJ-3989-based combination treatment. More specifically, the primary outcome is defined as absolute change from baseline in the percentage of HBsAg-positive hepatocytes at Week 40 for Panels 1 and 2. The record also lists serum response, seroclearance, liver-cell viral markers, and transcriptional activity as secondary measures.

Those aims do not amount to a reported result. The registry record does not give the primary mean change, the 80% confidence interval limits, or statistical tests. It therefore cannot support a statement about the direction, magnitude, or precision of the primary endpoint. Numerical secondary outcome results are also not reported in the registry record.

Even if a change estimate were available, a marker change would need to be interpreted in the context of the design and measurement procedures. In general, an observed before-and-after change does not on its own distinguish treatment effects from other influences over time. A between-panel comparison also requires attention to allocation and baseline comparability. Here, the allocation field says non-randomized, the official title says randomized, and the record cautions that the arms are not a like-for-like control comparison.

The record documents a completed Phase 2 study with enrollment of 24 and a range of planned virologic and tissue outcomes. It does not report enough numerical outcome information or analysis detail to establish efficacy, compare regimens, or determine how robust any estimated changes were. The record should therefore be read as describing the study’s design and endpoints, alongside limited safety counts, rather than as a complete statistical account of treatment effects.

13. Why This Trial Matters Statistically

This study is statistically notable because it centers on an intrahepatic marker measured by liver biopsy, rather than relying only on peripheral or serum measurements. The primary endpoint specifies a change in the percentage of HBsAg-positive hepatocytes between baseline and Week 40. The registry also lists measures of HBcAg-positive, cccDNA-positive, and pgRNA-positive hepatocytes, as well as transcriptional activity. These measures define a broad set of tissue and virologic questions.

That breadth makes transparent reporting especially important. The record lists 41 outcome measures, while reporting no analysis entries and no numerical primary or secondary results. Without results and a clear account of how multiple outcomes were handled, readers cannot distinguish a primary confirmatory analysis from exploratory assessments or evaluate the uncertainty around particular findings.

The allocation inconsistency is also consequential. The official title describes a randomized study, whereas the allocation field says non-randomized; the record further warns that the arms are not a like-for-like control comparison. Statistical comparisons depend on the design that actually generated the groups. A title alone cannot resolve that issue, and the registry record does not provide the allocation details needed to do so.

Finally, the small overall enrollment and limited group sizes in the safety listings mean that descriptive counts should be interpreted cautiously. The record’s sample-size planning illustration is not a substitute for a reported design justification or outcome analysis. In general, planning assumptions and observed results answer different questions: planning concerns what a study might detect under assumptions, while results describe what was estimated from the study data. The actual estimates needed for that assessment are not reported in the registry record.

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 has a central internal inconsistency: its official title calls the study randomized, but its allocation field says non-randomized. It also states that the arms are not a like-for-like control comparison. The record does not explain this discrepancy or provide enough allocation detail to establish how participants entered the panels. This limits interpretation of any between-panel contrast.

Enrollment is listed as 24, and the safety listings show groups with 10 participants at risk in Panels 1 and 2 and 4 in Panel 3. The primary analysis population size and the number with paired baseline and Week 40 biopsy measurements are not reported in the registry record. The number analyzed for each secondary outcome is also not reported.

The treatment descriptions are incomplete. The record lists JNJ-73763989, several nucleos(t)ide analog options, JNJ-56136379, and optional PegIFN-alpha-2a. It gives dosing details for Panels 1 and 2, but does not fully describe the treatment for every panel or the duration of optional PegIFN-alpha-2a. As a result, the full regimen contrast cannot be reconstructed from the record.

Most importantly, numerical primary and secondary outcome results are not reported in the registry record. The primary endpoint specifies a mean and an 80% confidence interval, but neither the estimate nor interval limits are listed. Missing-data procedures, analysis methods, multiplicity handling, and the sample-size justification are also not reported. These limitations prevent assessment of endpoint precision, analysis robustness, and the clinical meaning of any estimated change.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection — NCT04585789.
• Registry record last updated 2025-05-21; status last verified 2025-05.
• Results first posted 2024-03-05.
• 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 describes a completed, open-label, parallel-group, multicenter Phase 2 study in chronic hepatitis B virus infection, with enrollment of 24. Its primary endpoint is absolute change from baseline to Week 40 in the percentage of HBsAg-positive hepatocytes in Panels 1 and 2, summarized as a mean with an 80% confidence interval. The numerical endpoint result is not reported in the registry record.

Several secondary virologic and intrahepatic outcomes are listed, alongside safety counts for open-label and follow-up phases. The record lists no analysis entries. Its official title describes randomization, but the allocation field says non-randomized, and it cautions that the arms are not a like-for-like control comparison. Detailed statistical methods, missing-data handling, multiplicity procedures, and the sample-size justification are not reported in the registry record.