Open-Label Study of AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a in Subjects With Chronic Hepatitis B Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Study of AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a in Subjects With Chronic Hepatitis B Infection (NCT04980482), a randomized phase 2 study. The primary outcome is The Frequency and Severity of Treatment Emergent Adverse Events (TEAEs), Discontinuations Due to AEs and Lab Abnormalities After Dosing With AB-729 Plus Peg-IFNα-2a.

2. Clinical Question

3. Trial Design

This was a randomized, open-label, multicenter, parallel Phase 2 study in subjects with chronic hepatitis B infection. The registry lists an enrollment of 43 and a completed study status. The recorded study start is 2021-10-29, and the primary completion date is 2025-03-13. The registry record does not report the allocation ratio or the method used to generate or conceal the random sequence.

The treatment sequence began with AB-729 60 mg subcutaneously every 8 weeks plus nucleos(t)ide analogue therapy for 24 weeks. Participants were then randomized within Cohort A or Cohort B. In Cohort A, one group continued AB-729 with nucleos(t)ide analogue therapy and received Peg-IFNα-2a 180 mcg subcutaneously every week for 24 weeks; the other received nucleos(t)ide analogue therapy and Peg-IFNα-2a at the same dose and frequency for 24 weeks. In Cohort B, the corresponding post-randomization regimens used a 12-week course of Peg-IFNα-2a, with or without continued AB-729.

Because the study was open-label, participants and study personnel were not masked to assigned treatment. The record does not report why this design was selected or whether outcome assessors were separately masked. Nor does it describe the rationale for the cohort structure, the planned sample size, or any interim analyses. The posted primary endpoint is safety-focused, while the registry lists secondary outcomes involving hepatitis B surface antigen and other virologic markers, hepatitis B surface antibody seroconversion, eligibility to stop nucleos(t)ide analogue therapy, restarting therapy, relapse criteria and post-dose AB-729 concentrations.

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: 24 week lead-in period of imdusiran 60 mg SC every 8 weeks (Q8W) x4 doses added to ongoing SOC NA therapy

Lead-In Treatment

Consolidation Treatment

NA Only (Before NA Discontinuation)

NA Discontinuation/Did Not Discontinue

Analysis population for the primary outcome, as defined in the registry: Safety Lead-in 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.

Population: All Randomized

6. Primary Endpoint

The registry lists the primary outcome as The Frequency and Severity of Treatment Emergent Adverse Events (TEAEs), Discontinuations Due to AEs and Lab Abnormalities After Dosing With AB-729 Plus Peg-IFNα-2a, measured over Up to 124 weeks.

The primary endpoint is described as the frequency and severity of treatment-emergent adverse events, discontinuations due to adverse events and laboratory abnormalities after dosing with AB-729 plus Peg-IFNα-2a. The unit is participants, and the stated timeframe is up to 124 weeks. The primary population is the Safety Lead-in Population. The registry labels the measure as a count of participants and does not provide a further description of how severity or laboratory abnormalities were categorized.

Safety endpoints are used to characterize adverse events observed during treatment and follow-up. In general, counts can show how many participants were affected, while severity categories and reasons for discontinuation add context about the reported events. Such counts alone do not establish that a treatment caused an event: events occurring during a study may have other explanations, and an open-label study does not remove that uncertainty.

The stated primary endpoint combines several safety components rather than defining a single treatment-effect contrast. The registry record does not report a prespecified statistical comparison, an effect estimate, or a confidence interval for this endpoint. It also does not specify the detailed rules used to classify treatment-emergent events or laboratory abnormalities. The posted results therefore support a descriptive reading of participant counts, not a quantified comparison of the safety profiles of the randomized groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It identifies a randomized, open-label, parallel study and posts participant counts for safety categories, but it reports no statistical analyses. No model, test, adjustment method, or inferential estimate is described. The registry record also does not report a statistical analysis plan, sample-size justification, allocation ratio, interim analyses, missing-data methods, or rules for handling participants who discontinue or change treatment.

What do participant counts describe?

The primary endpoint uses participants as its unit. A participant count describes how many people in a stated group were recorded as affected by an event category. It is not the same as an event count: one person may experience more than one event, while the participant count records whether people were affected. The posted results distinguish a serious-event category from an other-event category. The registry record does not provide additional operational definitions for those categories in the primary endpoint description.

Counts should be read together with the relevant group size. They show the observed experience in the recorded participants, but do not by themselves estimate how often an event would occur in a broader population. In general, statistical uncertainty describes how much an estimate might vary because the observed participants are only a sample. A confidence interval is one way to express that uncertainty around an estimate. No confidence intervals are posted for these safety counts.

Why does randomization matter?

In general, random assignment is intended to make treatment groups comparable in expectation, which can support causal comparisons when the study is designed and analyzed appropriately. The registry states that randomization occurred after the shared initial treatment period. It does not post the randomized-group outcome analyses needed to assess a comparative effect. The registry also does not report the allocation ratio or the sequence-generation and concealment procedures. Consequently, the design description alone cannot establish that the observed group counts differ because of treatment.

The trial was open-label. In general, knowledge of assigned treatment can influence reporting, assessment or decisions about discontinuation, depending on the outcome and study procedures. The record does not describe whether any outcome assessments were masked or how potential reporting differences were addressed. These are design considerations, not proof that any specific count was biased.

How should the cohort counts be interpreted?

The registry reports Lead-In Treatment separately from Cohort A1, Cohort A2, Cohort B1 and Cohort B2. The arm descriptions indicate a shared initial treatment period followed by randomized treatment regimens that differ by continued AB-729 and by Peg-IFNα-2a duration across cohorts. Those distinctions matter: group counts should not be treated as if every group received the same regimen or had the same treatment duration. The posted data do not supply a formal analysis accounting for cohort, treatment exposure or follow-up.

In general, over-dispersion occurs when count variation is greater than a chosen statistical model expects; ignoring it can make uncertainty estimates too small. The posted primary measure is a count of participants, and no model or dispersion parameter is reported. There is therefore no basis to claim that a model accounting for over-dispersion was or was not used.

What can planning illustrations tell readers?

Any sample-size figures associated with an observed effect are planning illustrations, not observed power and not evidence that the trial was adequately powered. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. These are generic calculation assumptions, not a reported design justification for this study. The record does not state that the trial was planned around those assumptions or that a particular sample-size target was selected on that basis. Moreover, the primary safety outcome has several categories or time points and is not reduced to one comparison in the posted analysis, so a single effect-based planning calculation would not summarize all safety questions.

For this study, the most defensible statistical reading is therefore descriptive. The registry supplies counts and group sizes but no inferential results. Without a reported analysis plan and outcome comparisons, readers cannot assess precision through confidence intervals, statistical significance through tests, or the impact of missing data and multiplicity.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcome families: change from baseline in HBsAg and other virologic markers at each time point; HBsAb seroconversion; eligibility to stop nucleos(t)ide analogue therapy after Week 24 of follow-up; restarting therapy after discontinuation; protocol-defined clinical and viral relapse; and post-dose plasma concentrations of AB-729 antisense and its listed metabolites. It reports seven outcome measures, but no analyses. The record does not describe a multiplicity strategy for interpreting results across outcomes, time points, cohorts or treatment comparisons. Without such a plan and posted estimates, the listed outcomes cannot be treated as a set of confirmatory findings.

Missing-data handling is not reported in the registry record. The record does not explain how participants with incomplete follow-up, missing laboratory measurements, treatment discontinuation or unavailable outcome assessments were handled in analysis. It also does not state whether any imputation or sensitivity analyses were planned. As a result, the effect of missing information on the posted counts cannot be assessed.

The primary endpoint identifies the Safety Lead-in Population, but the registry does not give a broader analysis-population definition or explain which participants were included in each analysis. The posted adverse-event groups have their own at-risk counts, but the record does not explain whether follow-up or exposure differed across those groups. It also does not report a statistical analysis plan, interim analyses, or procedures for selecting among outcomes. These omissions limit interpretation of both the safety summaries and the unreported secondary outcomes.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bilateral chronic rhinonasal sinusitis with polyposis (10.0%), nasal septum deviation (10.0%), ureterolithiasis (8.3%).

The serious-event counts are 0 of 43 in Lead-In Treatment, 1 of 12 in Cohort A1, 0 of 13 in Cohort A2, 0 of 8 in Cohort B1 and 1 of 10 in Cohort B2. The record reports no deaths in these groups. These counts describe participants recorded in each category; they do not establish whether a treatment caused an event or whether one group differs statistically from another.

The registry also lists Bilateral Chronic Rhinonasal Sinusitis with Polyposis (10.0%), Nasal Septum Deviation (10.0%) and Ureterolithiasis (8.3%) among the serious adverse event terms. Those percentages are reproduced as listed, but the record does not identify a cohort for each term in the summary. They should not be combined with the group counts to infer an unreported rate or comparison.

In general, serious adverse events are distinct from other recorded adverse events, and a serious-event count is not a complete measure of tolerability. The record does not provide event-level timing, recurrence, severity detail or a comparative statistical analysis. The other-event counts are also participant counts, not necessarily counts of individual events. Thus these figures offer a descriptive safety account, not a causal or comparative conclusion.

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

The posted results describe adverse events recorded in a randomized, open-label Phase 2 study of AB-729, nucleos(t)ide analogue therapy and Peg-IFNα-2a. They show the number of participants affected in the serious and other event categories across the listed lead-in and cohort groups. The registry also reports three serious adverse event terms with percentages and no deaths in the listed groups. Those details provide a limited account of observed safety events in the recorded study populations.

They do not establish that AB-729 or Peg-IFNα-2a caused a particular event. They do not demonstrate that one regimen is safer or less safe than another, because no statistical comparison or uncertainty estimate is posted. The groups differ in size and in their post-randomization regimens, and the record does not provide a comparative analysis accounting for those differences.

The primary endpoint is safety-focused; it does not directly answer whether viral markers changed or whether participants could stop nucleos(t)ide analogue therapy. Although the registry lists secondary outcomes addressing those questions, it posts no analyses for them. The record also does not report a sample-size justification, missing-data approach, multiplicity method or analysis plan. Conclusions about precision and the robustness of findings are therefore constrained.

In general, a completed study is not the same as a study with every outcome analyzed or posted. Here, the registry status is completed, but the posted results remain descriptive. The evidence represented by these entries is the set of recorded counts and listed event terms, not a demonstrated treatment effect, a definitive safety comparison or a result about antiviral activity.

13. Why This Trial Matters Statistically

This trial raises several important statistical issues for clinical researchers. Its design includes a shared treatment period followed by randomized groups with different regimens, including different Peg-IFNα-2a durations across Cohort A and Cohort B. That structure makes it important to distinguish the populations, treatment periods and outcome definitions before comparing counts. A pooled summary without those distinctions could obscure differences in exposure or follow-up.

The primary outcome is a multi-component safety measure involving treatment-emergent adverse events, discontinuations due to adverse events and laboratory abnormalities. The registry posts participant counts but no formal analysis that combines or separately evaluates those components. Without prespecified definitions and a reported analysis plan, it is difficult to determine how the components were intended to support a single primary conclusion.

The study is randomized but open-label, and the recorded safety groups are limited in size. These features do not invalidate descriptive counts, but they make careful reporting of uncertainty and outcome assessment procedures especially relevant. The registry does not provide confidence intervals, hypothesis tests or a comparison of randomized groups, so the posted counts cannot answer whether observed differences exceed what might arise from chance.

Finally, the registry lists multiple secondary outcomes and time-point-based measures but reports no analyses. This illustrates why outcome multiplicity, missing-data handling and clear analysis populations matter. The record provides a useful description of study structure and reported safety counts, while leaving the statistical evidence needed for comparative interpretation unavailable.

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 gives limited detail about the conduct and analysis of this trial. It does not report the planned sample size or its justification, the allocation ratio, random-sequence generation or allocation concealment. Although the study is described as randomized and open-label, the record does not clarify whether any outcome assessors were masked. The statistical analysis plan, interim analyses and analysis methods are not reported.

The posted primary outcome is a count of participants for a safety endpoint with several components. The record does not specify detailed event definitions, severity grading, laboratory thresholds, or how discontinuations due to adverse events were analyzed. No statistical analysis is posted, and no confidence intervals or comparative estimates are available. Consequently, the precision of the group counts and the significance of differences cannot be assessed.

The registry lists several secondary outcomes but does not post their results or explain multiplicity control. Missing-data methods and the handling of incomplete follow-up or discontinuation are also not reported. Although counts are presented by lead-in and cohort groups, the record does not provide enough information to assess differences in follow-up or treatment exposure across those groups. The serious adverse event terms are listed with percentages but without group attribution in the summary.

These limitations concern what the registry reports; they do not show that particular procedures were absent from the underlying study. The registry record does not report whether such procedures were conducted elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open-Label Study of AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a in Subjects With Chronic Hepatitis B Infection — NCT04980482.
• Registry record last updated 2026-04-29; status last verified 2026-04.
• Results first posted 2026-04-29.
• 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

NCT04980482 is a completed, randomized, open-label, multicenter, parallel Phase 2 study in chronic hepatitis B infection. It enrolled 43 participants and investigated AB-729 with ongoing nucleos(t)ide analogue therapy and short courses of Peg-IFNα-2a. After an initial treatment period, participants in Cohort A and Cohort B were randomized to regimens with or without continued AB-729; the Peg-IFNα-2a course differed between cohorts.

The primary endpoint concerns treatment-emergent adverse events, discontinuations due to adverse events and laboratory abnormalities, assessed up to 124 weeks in the Safety Lead-in Population. The registry posts serious and other adverse-event participant counts by group, lists serious-event terms and reports no deaths in the listed groups. It lists secondary virologic, seroconversion, treatment-discontinuation, relapse and drug-concentration outcomes, but reports no statistical analyses. The analysis plan, sample-size justification, missing-data procedures and multiplicity approach are not reported in the registry record.