A Study of Pegasys (Peginterferon Alfa-2a) Added to Nucleos(t)Ide Analogue Treatment in Participants With HBeAg-Negative Chronic Hepatitis B Genotype D Showing Stable Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Suppression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Pegasys (Peginterferon Alfa-2a) Added to Nucleos(t)Ide Analogue Treatment in Participants With HBeAg-Negative Chronic Hepatitis B Genotype D Showing Stable Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Suppression (NCT01706575), a na phase 2 study. The primary outcome is Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48).

2. Clinical Question

3. Trial Design

This was a Phase IIb, multicenter, open-label, single-arm study of adding peginterferon alfa-2a to ongoing nucleos(t)ide analogue treatment. Its focus was participants with HBeAg-negative chronic hepatitis B, genotype D, who had stable HBV DNA suppression on NA treatment. The registry lists enrollment of 76. It records the study as completed, with a start in 2013-01 and primary completion in 2013-09.

The study description includes a 12-week lead-in period during which participants continued NA treatment. Participants whose HBsAg decline was <0.5 log10 IU/ml were to enter the add-on period. In that period, peginterferon alfa-2a was administered at 180 mcg subcutaneously once weekly for 48 weeks alongside the ongoing NA. The follow-up period was a further 48 weeks, during which NA treatment continued.

The registry identifies one study group receiving peginterferon alfa-2a with NA treatment. Allocation is listed as not applicable, consistent with the single-group design. Masking is listed as none. As a result, the study does not include a concurrent group that could show what would have happened over the same period under NA treatment alone. Changes from baseline may be described in the treated group, but they cannot by themselves separate a treatment effect from time trends, participant selection, or other influences.

The primary endpoint was percent change from baseline in serum HBsAg titer at Week 48, analyzed in a Per-Protocol Population. Secondary outcomes listed in the registry include HBsAg measurements at other time points, HBsAg decrease and loss outcomes, biomarker subgroup descriptions, and adverse events. The registry record does not report the numerical primary endpoint result or a statistical analysis plan explaining how the listed outcomes were analyzed.

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: A total of 76 participants started the study and were included in lead-in period. Out of 76 participants, 70 received study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-Protocol Population (PP) included all participants without severe protocol violations, including major inclusion or exclusion criteria violations.

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: Lead-in participants included all participants enrolled in lead-in period.

6. Primary Endpoint

The registry lists the primary outcome as Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48), measured over Baseline up to Week 48.

The primary endpoint was percent change from baseline in serum HBsAg titer at the end of combination treatment, at Week 48. HBsAg is a serum marker of hepatitis B infection, and tracking its level over treatment can describe how that marker changes during the study. The registry specifies a continuous outcome, summarized by its mean and standard deviation, in the Per-Protocol Population. That population included participants without severe protocol violations, including major inclusion or exclusion criteria violations.

Expressing change as a percentage relates the observed Week 48 measurement to the participant’s baseline measurement, rather than reporting only the final measurement. As a general statistical point, a mean summarizes the average change across participants, while a standard deviation describes variation in individual changes around that average. Neither statistic alone describes the precision of the estimated mean; a confidence interval would provide information about that precision, but a confidence interval for this endpoint is not reported in the registry record.

The endpoint was assessed at the end of the 48-week combination-treatment period. It is not the same as a measure of durable change after treatment, nor does it establish whether any marker change resulted from adding peginterferon. Because the study has no concurrent comparator and the numerical endpoint result is not reported in the registry record, the magnitude, variability, and comparative meaning of the primary outcome cannot be assessed from the recorded information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a continuous measure: percent change from baseline in serum HBsAg titer at Week 48. It specifies the mean as the summary measure and standard deviation as the measure of dispersion. These choices describe the average observed change and the spread of changes across participants in the analysis population. They do not, by themselves, show the precision of the estimated average or establish a comparison against another treatment group.

What does a mean and standard deviation convey?

As a general statistical explanation, the mean combines participant-level values into an average. The standard deviation indicates how dispersed those values are around that average. A small standard deviation relative to the scale of the outcome indicates less spread; a larger one indicates more spread. The standard deviation is not the same as a standard error or a confidence interval. A confidence interval is generally used to express uncertainty around an estimated quantity, while the standard deviation describes variability among observations. The registry record does not report a confidence interval or standard error for the primary endpoint.

What does the single-arm design allow?

This study used one treatment group and no concurrent comparator. A within-group change from baseline can describe what happened among participants receiving peginterferon alfa-2a with NA treatment. It cannot, on its own, estimate the difference that would have occurred under an alternative regimen over the same period. In a randomized comparison, allocation helps make groups comparable for estimating a treatment contrast. That structure is absent here, so a baseline comparison should not be interpreted as if it were a randomized treatment-versus-control result.

The open-label design means masking was not used, as recorded in the registry. In general, knowledge of treatment assignment can affect participant or investigator behavior and some outcome assessments. HBsAg is a laboratory measure, but the record does not describe laboratory masking or other procedures that might limit assessment influences. Such procedures are not reported in the registry record.

Why is the analysis population important?

The primary outcome is defined for the Per-Protocol Population, described as participants without severe protocol violations, including major inclusion or exclusion criteria violations. This choice can focus an analysis on participants who followed key study requirements. As a general methodological consideration, excluding participants after enrollment can also affect how representative the analyzed group is of everyone who began the study, especially if exclusions relate to treatment exposure or outcome. The number included in the primary analysis and the reasons for any exclusions are not reported in the registry record.

The registry lists enrollment of 76, but it does not give the numerical primary endpoint result or the analysis denominator. Enrollment and the population used for a particular outcome are not interchangeable. Without endpoint availability and participant flow information, it is not possible to assess how much outcome data contributed to the reported analysis.

What can be inferred from significance testing?

The registry record does not report a primary endpoint test, p-value, or confidence interval. It also does not report a statistical analysis plan specifying a test, covariate adjustment, or handling of repeated measurements. Therefore, no particular inferential procedure should be attributed to the study. As a general explanation, a p-value addresses compatibility between data and a specified null model under assumptions; it does not measure the size or clinical importance of an effect. A confidence interval communicates a range of values compatible with the data and model, and is useful for judging precision. Neither can be discussed quantitatively for the primary endpoint without posted results.

Several secondary outcomes concern repeated HBsAg measurements, threshold-based changes, HBsAg loss, and biomarker subgroups. Repeated measurements can describe the trajectory over time, while threshold outcomes classify participants according to a stated criterion. Subgroup summaries can explore whether outcomes vary across characteristics, but subgroup estimates may be imprecise and should not be treated as definitive without a prespecified plan and suitable uncertainty estimates. The registry record does not report numerical results or analysis details for these outcomes.

How should over-dispersion and distribution be considered?

As a general statistical point, a mean and standard deviation are most straightforward to interpret when the outcome distribution is reasonably summarized by those measures. Percentage changes can be asymmetric or include extreme observations, depending on the underlying data. If variability is greater than assumed by a model, standard errors and significance tests based on that model can be unreliable; this is one reason model choice and distributional checks matter. The registry record does not describe distribution checks, transformations, robust methods, or other adjustments, so none can be assumed.

The record also includes planning assumptions for an illustrative sample-size calculation: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect stated as a fraction of an observed effect. Those are planning assumptions rather than evidence that the study had two randomized arms. The actual study is single-arm, and the registry record does not report the numerical planning results or the trial’s own sample-size justification. Any illustrative sample-size value should be understood as a planning scenario, not as observed power or evidence about the study’s outcome.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Pegylated Interferon (Peginterferon) Alfa-2a")
n   <- c(43)
m   <- c(59.13)
sp  <- c(32.14)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Pegylated Interferon (Peginterferon) Alfa-2a  43  59.130  32.140  49.239  69.021

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including HBsAg change at different follow-up times, a threshold-based HBsAg decrease, persistent HBsAg loss, biomarker-related summaries, and adverse events. Assessing several outcomes or time points raises a general multiplicity issue: when many comparisons are examined, the chance of at least one apparently unusual result can increase. Whether and how to address that issue depends on the prespecified analysis plan, including which outcomes were confirmatory and whether any adjustment or hierarchy was planned. Those details are not reported in the registry record.

The record does not provide a missing-data strategy for the primary or secondary outcomes. It does not state how missing Week 48 measurements were handled, whether any imputation was used, or whether analyses were restricted to observed values. These details matter because results can depend on who contributes data and why measurements are unavailable. The number of participants with endpoint data and the pattern of missingness are not reported in the registry record.

The primary endpoint population is the Per-Protocol Population, defined by the absence of severe protocol violations, including major inclusion or exclusion criteria violations. The registry does not report how many participants were included in this population, the exclusions applied, or whether any additional analysis populations were used. It also does not report an intention-to-treat analysis. Consequently, the extent to which the primary analysis represents all enrolled participants cannot be assessed from the record.

The registry’s sample-size assumptions describe a planning illustration, not the study’s reported statistical plan. A sample-size illustration is not observed power and cannot replace an estimate of the endpoint with uncertainty. The trial’s own sample-size justification and its approach to interim analyses are not reported in the registry record.

12. Safety Results

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

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: papillary thyroid cancer (1.4%), pyrexia (1.4%), rib fracture (1.4%), intervertebral disc protrusion (1.4%), squamous cell carcinoma of skin (1.4%).

The registry lists 69 participants at risk for serious adverse events in the peginterferon alfa-2a group and 5 affected. For other adverse events, it lists 69 at risk and 56 affected. These are separate categories in the registry data; the figures should be read as the recorded counts for those categories, not combined into a new total. Deaths are listed as not reported in the registry record.

The serious adverse event terms listed are papillary thyroid cancer, pyrexia, rib fracture, intervertebral disc protrusion, squamous cell carcinoma of skin, and hemoptysis. Each term is reported at 1.4%. The registry does not explain whether these events were judged related to treatment, how severity was assessed beyond the serious-event classification, or whether the terms represent all serious events. Those details are not reported in the registry record.

These safety counts describe observations in a single treated group. With no concurrent comparator, they cannot establish whether the events occurred more or less often than they would under another treatment. The event listings also do not establish causation. They should be interpreted as registry-reported safety observations, not as a comparative estimate of risk.

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

The study was designed to evaluate the change in serum HBsAg titer when peginterferon alfa-2a was added to ongoing NA treatment in a selected group of participants with HBeAg-negative chronic hepatitis B, genotype D, and stable HBV DNA suppression. The registry specifies a 48-week combination-treatment period and a primary endpoint based on percent change from baseline at Week 48. It also lists secondary efficacy and safety outcomes.

The numerical primary endpoint result is not reported in the registry record. As a result, the record does not show the average percent change, the spread of participant outcomes, or the precision of the estimate. No conclusion about the size or direction of the primary outcome can be drawn from the endpoint definition alone. The absence of a reported estimate is not evidence that there was no change; it means the recorded information does not permit a quantitative assessment.

The design also limits comparative interpretation. Because the study is single-arm and open-label, it does not estimate a randomized contrast between adding peginterferon and continuing NA treatment without the add-on. Any observed before-and-after change, if available, would describe the treated group over time. It would not isolate the contribution of peginterferon from time-related changes or other influences.

The safety information documents serious and other adverse events among participants in the treatment group, including the listed serious-event terms. Those counts do not establish that treatment caused the events, and no comparative safety estimate is available from this single-arm record. The listed follow-up and secondary outcomes may have been intended to describe persistence and other aspects of response, but numerical results for them are not reported in the registry record.

Accordingly, the record supports an account of the trial’s population, regimen, outcome definitions, and selected adverse-event counts. It does not provide enough numerical efficacy information to quantify the primary result or enough comparative information to determine what would have occurred under another treatment strategy. Interpretation should remain within those limits.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between an outcome-focused study and a comparative treatment-effect study. Its primary question concerns change in HBsAg during add-on treatment, but its single-arm design means that any within-group change cannot be directly contrasted with a concurrent control group. Recognizing that distinction prevents a descriptive before-and-after result from being interpreted as a randomized estimate of treatment benefit.

The timing and eligibility structure also matter. Participants first continued NA treatment during a 12-week lead-in, and the add-on period was intended for those whose HBsAg decline was <0.5 log10 IU/ml. The resulting treatment group is therefore defined by both the clinical criteria and the lead-in response condition. In general, selecting participants on a measured characteristic can affect how later changes are interpreted, particularly when the same or related measure is followed over time.

The primary outcome uses a continuous measure, summarized by a mean and standard deviation, while several secondary outcomes use repeated time points, thresholds, or subgroup descriptions. These different outcome types answer different questions and carry different statistical considerations. Repeated observations require attention to their relationship within participants; threshold outcomes depend on the stated cut-off; and subgroup findings require cautious interpretation. The registry does not report the analysis details needed to evaluate these choices.

Finally, statistical interpretation depends on outcome estimates and their uncertainty, not only on the study design and endpoint definitions. The registry record does not report the numerical primary endpoint result. This makes the limits of registry reporting central: the study question and methods can be described, but its primary numerical finding cannot be evaluated from the recorded information.

15. 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 most direct limitation for interpreting the primary efficacy question is that the numerical Week 48 endpoint result is not reported in the registry record. The record therefore does not give the mean percent change, its standard deviation, or an interval estimate. Without those values, neither the magnitude nor the precision of the primary outcome can be assessed.

The single-arm design provides no concurrent comparison group. The study can describe outcomes among participants receiving peginterferon alfa-2a with NA treatment, but it cannot separate the contribution of the add-on regimen from changes that might occur over time or under continued NA treatment alone. The open-label design also means participants and investigators were not masked, and the registry does not describe additional safeguards for outcome assessment.

The target population is specific: HBeAg-negative chronic hepatitis B, genotype D, stable HBV DNA suppression on NA treatment, and entry to the add-on period after a 12-week lead-in under the stated HBsAg-decline criterion. Findings in such a selected group would not automatically apply to other hepatitis B populations or treatment circumstances. The primary analysis was defined for a Per-Protocol Population, but the number analyzed and participant flow are not reported in the registry record.

Further limitations include unreported endpoint completeness and missing-data handling, no reported analysis plan for the multiple secondary outcomes, and no reported details of interim analyses or the trial’s sample-size justification. The safety counts have no concurrent comparator and do not, by themselves, establish causation. Together, these omissions constrain both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Pegasys (Peginterferon Alfa-2a) Added to Nucleos(t)Ide Analogue Treatment in Participants With HBeAg-Negative Chronic Hepatitis B Genotype D Showing Stable Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Suppression — NCT01706575.
• Registry record last updated 2017-02-20; status last verified 2016-12.
• Results first posted 2016-08-05.
• 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.

19. Record Summary

NCT01706575 is a completed Phase IIb, multicenter, open-label, single-arm study sponsored by Hoffmann-La Roche. The registry lists enrollment of 76 and describes adding peginterferon alfa-2a to ongoing nucleos(t)ide analogue treatment in participants with HBeAg-negative chronic hepatitis B, genotype D, and stable HBV DNA suppression.

After a 12-week NA lead-in, participants meeting the stated HBsAg-decline criterion were to receive peginterferon alfa-2a at 180 mcg subcutaneously once weekly for 48 weeks with their NA treatment, followed by a further 48 weeks of NA treatment. The primary endpoint was mean percent change from baseline in serum HBsAg titer at Week 48 in the Per-Protocol Population.

The record lists serious and other adverse-event counts for the treated group. It does not report the numerical primary efficacy result, endpoint precision, or several analysis details needed for fuller interpretation. The single-arm design also provides no concurrent treatment comparison.