This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety, Tolerability, Pharmacokinetics and Antiviral Activity of IONIS-HBVRx in Treatment-Naïve Patients With Chronic HBV Infection (NCT02981602), a randomized phase 2 study. The primary outcome is Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02981602 |
| Phase | Phase 2 |
| Condition | Hepatitis B, Chronic Hepatitis B Atypical |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 31 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Treatment-naïve patients with chronic HBV infection. The registry lists Hepatitis B and Chronic Hepatitis B Atypical as conditions. The safety population is defined as randomized participants who received at least 1 dose of GSK3228836 or placebo.
Intervention
IONIS-HBVRx, described as ascending multiple doses by subcutaneous injection. The registry’s safety outcome uses the name GSK3228836; it also records that Cohort 3 received 300 mg rather than 450 mg, as decided by the sponsor.
Comparator
Placebo, described as sterile normal saline (0.9% NaCl) in a calculated volume intended to match the active comparator. Participants were assigned in a randomized, parallel-group study.
Primary question
How many participants had serious adverse events or non-serious adverse events meeting the registry’s threshold of at least 5%, through Day 211? This is a count-based safety question, not a single measure of antiviral activity.
The primary outcome concerns the occurrence of adverse events during the study period. The registry defines an adverse event as an unfavorable, unintended sign, symptom, or disease temporally associated with the study or investigational drug, whether or not it is considered related to the drug. It classifies an event as serious when it meets specified criteria, including death, life-threatening events, hospitalization or its prolongation, disability or incapacity, congenital anomaly or birth defect, or another important medical event according to medical judgment.
The posted outcome is grouped into serious events and non-serious events meeting the stated frequency threshold. It does not, by itself, establish whether an event was caused by treatment. The registry gives counts by dose cohort and placebo group. It does not report a single pooled treatment-versus-placebo estimate for this outcome, and a single comparison is not calculated because the primary outcome has several categories or time points.
The study also registered secondary measures of HBV DNA, HBsAg, and HBeAg at Day 29 and Week 31. Those measures frame additional questions about viral markers, but their numerical results are not included in the registry record described for this analysis. The central question addressed by the posted primary outcome remains the count of participants with specified adverse-event categories through Day 211.
3. Trial Design
This was a Phase 2, randomized, triple-masked, parallel-group, placebo-controlled, dose-escalation study. It enrolled 31 participants and is listed as completed. The registry records a start date of 2017-02-24 and a primary completion date of 2019-12-18. GlaxoSmithKline is listed as the sponsor.
The active intervention is named IONIS-HBVRx in the trial title and brief description. The arm descriptions refer to ascending multiple doses administered by subcutaneous injection. The primary safety outcome identifies the active treatment as GSK3228836, and the official title identifies the investigational compound as ISIS 505358. These names appear in the registry record; the information does not establish any further relationship among the names.
The comparator was sterile normal saline (0.9% NaCl), in a calculated volume intended to match the active comparator. Randomization indicates that treatment assignment used a chance-based allocation process; the registry record does not report the allocation ratio or the detailed randomization procedure. Triple masking indicates that masking was used, but which groups of people were masked and how masking was maintained are not reported in the registry record.
The study used dose cohorts. The registry records that Cohort 3 participants received GSK3228836 300 mg instead of 450 mg as a sponsor decision, and that Cohort 2 and Cohort 3 were combined for the primary safety outcome. The posted safety groups also distinguish Cohort 1 at 150 mg, Cohorts 2 and 3 at 300 mg, Cohort 4 at 300 mg, and placebo groups. This structure matters when reading the counts: they are presented by these cohort groupings rather than as one undifferentiated active-treatment group.
The registry lists 35 outcome measures and 15 analyses. It names secondary outcomes covering HBV DNA viral load in plasma, HBsAg in serum, HBsAg loss, HBeAg loss among participants positive at baseline, and serum HBeAg concentration among participants positive at baseline. Several are assessed at Day 29 and Week 31. The numerical results for these secondary outcomes are not reported in the registry record, so they cannot be interpreted alongside the safety counts.
The registry does not report the planned allocation ratio, the intended sample size by cohort, or the detailed sequence and timing of dose escalation beyond the cohort descriptions. Those features should not be inferred from the enrollment total or from the arm labels.
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 31 participants were enrolled and received either GSK3228836 or placebo. In Cohort 3 participants were administered GSK3228836 300 milligram \[mg\] instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
Overall Study
| Stage | Cohort 1 GSK3228836 150 mg | Cohort 2 and Cohort 3 GSK3228836 300 mg | Cohorts 1-3 Placebo | Cohort 4 GSK3228836 300 mg | Cohort 4 Placebo |
|---|---|---|---|---|---|
| STARTED | 6 | 12 | 6 | 5 | 2 |
| COMPLETED | 6 | 12 | 6 | 4 | 2 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 0 |
Reasons for not completing this period:
| Reason | Cohort 1 GSK3228836 150 mg | Cohort 2 and Cohort 3 GSK3228836 300 mg | Cohorts 1-3 Placebo | Cohort 4 GSK3228836 300 mg | Cohort 4 Placebo |
|---|---|---|---|---|---|
| Adverse Event | 0 | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Population includes all randomized participants who received at least 1 dose of GSK3228836 or placebo. In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
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: In Cohort 3 participants were administered GSK3228836 300 mg instead of 450 mg as per sponsor's decision, hence Cohort 2 and Cohort 3 have been combined.
| Characteristic | Unit | Cohort 1 GSK3228836 150 mg | Cohort 2 and Cohort 3 GSK3228836 300 mg | Cohorts 1-3 Placebo | Cohort 4 GSK3228836 300 mg | Cohort 4 Placebo | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 6 | 12 | 6 | 5 | 2 | 31 | |
| Age, Continuous | Years | 42.5 (SD 11.22) | 42.6 (SD 14.12) | 49.3 (SD 12.66) | 48.4 (SD 7.40) | 37.0 (SD 2.83) | 44.5 (SD 11.90) |
| Sex: Female, Male: Female | Participants | 3 | 8 | 2 | 1 | 1 | 15 |
| Sex: Female, Male: Male | Participants | 3 | 4 | 4 | 4 | 1 | 16 |
| Race/Ethnicity, Customized: Race – Asian | Participants | 6 | 12 | 6 | 5 | 2 | 31 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=5%), measured over Up to Day 211.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with serious adverse events and non-serious adverse events meeting the registry’s threshold of at least 5%, through Day 211. Its unit is participants. A participant count records how many people met an event definition; it is not a measure of how many separate events occurred, how long an event lasted, or how severe an event was beyond the serious/non-serious classification.
The registry defines an adverse event broadly as an unfavorable and unintended sign, symptom, or disease temporally associated with the study or investigational drug. The event need not be judged related to the investigational product to meet this definition. The serious-event definition includes specified outcomes such as death, a life-threatening event, hospitalization or prolonged hospitalization, disability or incapacity, congenital anomaly or birth defect, and another important medical event according to medical judgment.
As a general statistical rationale, safety outcomes are used to describe the kinds and frequency of harms observed during a trial. Reporting participant counts can make uncommon events visible even when a study is not designed to estimate treatment effects precisely. However, counts alone do not show whether treatment caused an event, and sparse counts can leave considerable uncertainty about the underlying event frequency.
The registry reports serious events and non-serious events meeting the threshold as distinct categories. It does not supply one combined effect estimate or a single treatment comparison for the primary outcome in the registry record. The endpoint should therefore be read as a set of cohort-specific safety counts over the stated period, rather than as a definitive comparative estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The safety counts differ across the cohort groups, but these are descriptive observations. In Cohort 1, 0 of 6 participants had a serious adverse event, while 5 of 6 had a non-serious adverse event meeting the registry’s threshold. In the combined Cohort 2 and Cohort 3 group, 1 of 12 participants had a serious adverse event and 6 of 12 had a qualifying non-serious adverse event. No deaths were recorded in either group.
In the placebo groups from Cohorts 1–3, 0 of 6 participants had a serious adverse event and 2 of 6 had a qualifying non-serious adverse event. In Cohort 4 at 300 mg, 0 of 5 participants had a serious adverse event and 3 of 5 had a qualifying non-serious adverse event. In the Cohort 4 placebo group, 0 of 2 participants had a serious adverse event and 0 of 2 had a qualifying non-serious adverse event. No deaths were recorded in either Cohort 4 group.
These counts should not be treated as a clean head-to-head comparison. The groups are arranged by cohort and dose, and Cohort 2 and Cohort 3 are combined in the registry’s safety population description. The fact that a group has more participants with an event does not, on its own, identify a treatment effect. The group sizes are small, and the registry does not report an adjusted estimate, a confidence interval, or a statistical test for a single primary-outcome comparison in the registry record.
The registry lists “Alanine aminotransferase increased” as a top serious-event term with 8.3%. That term-level entry should be read as the registry’s posted value, not as a substitute for the broader serious-event participant counts. The registry entries do not specify its group attribution or give further detail about the event, so those details are not reported in the registry record.
The primary endpoint spans follow-up through Day 211, but the posted counts do not describe when events began, how long they continued, or whether they resolved. They also do not provide severity grades beyond the serious/non-serious distinction in the primary outcome description. A reader can identify the number of participants counted in each group, but cannot infer the timing, individual clinical course, or causal relationship of events from those counts alone.
The registry describes the safety population as all randomized participants who received at least 1 dose of GSK3228836 or placebo. That definition is important: the outcome counts refer to this population, not necessarily to every randomized participant. The registry does not report additional outcome-specific missingness information in the registry record. Accordingly, the counts are best interpreted as the posted descriptive safety results for the defined population, with limited precision and without a reported comparative analysis.
9. Statistical Methods Explained
The primary outcome is a count of participants, so the basic data are discrete: for each group, a participant either meets the specified event definition or does not. This differs from a continuous outcome such as a laboratory concentration, which can take a range of measured values. As a general statistical explanation, participant counts are often presented with the number of people assessed because the count’s meaning depends on the group size. The registry lists both the number at risk and the number affected for each safety category.
For a binary event outcome, a common general approach is to estimate the event proportion within each group and then compare groups using a difference or ratio. Such estimates can be accompanied by confidence intervals. A confidence interval describes the range of values compatible with the observed data under the assumptions of the method; it helps communicate precision, rather than guaranteeing that the true value lies in that range. These general methods do not imply that a particular analysis was conducted in this trial. A comparative estimate and confidence interval for the primary safety outcome are not reported in the registry record.
Counts can be especially imprecise when group sizes and event numbers are small. As a general matter, a change in the outcome status of one participant can make a noticeable difference to a small group’s observed event proportion. A count of zero also does not establish that the underlying risk is zero; it means that no affected participants were recorded in that group during the stated observation period. The registry’s zero counts should therefore be read as observed counts, not as proof that an event cannot occur.
The primary outcome is not reduced to one comparison because it includes several categories or time points. This means no single p-value or effect estimate is presented as the primary result in the registry record. It would be misleading to select one category or cohort after seeing the counts and treat it as though it represented the full outcome. The posted categories should instead be read separately, respecting the registry’s grouping and definitions.
The registry’s primary outcome distinguishes serious adverse events from non-serious adverse events meeting a threshold of at least 5%. These are not interchangeable endpoints. Seriousness is defined using medical and regulatory criteria, while the non-serious category has a stated frequency threshold. A participant could contribute to more than one event description in an underlying safety dataset, but the registry entries do not explain whether or how overlapping event categories were handled. That detail is not reported in the registry record.
The population definition also affects the interpretation. The safety population includes randomized participants who received at least 1 dose of GSK3228836 or placebo. As a general methodological point, an analysis population defined by treatment receipt may differ from a population that includes all randomized participants regardless of whether treatment began. The registry’s stated definition is the one relevant to these safety counts. Further details about exclusions, adherence, and outcome-specific analysis populations are not reported in the registry record.
The study was randomized and placebo-controlled. In general, randomization can help balance prognostic characteristics across assigned groups, while a placebo comparator can support interpretation of outcomes against a group not receiving the active investigational drug. These design features do not remove uncertainty, especially in small groups, and they do not make an observed difference causal by themselves. Here, the registry reports cohort-specific counts but not a single inferential comparison for the primary safety outcome. The registry entries also do not include baseline characteristics needed to assess how similar the groups were in the posted safety population.
Masking is listed as triple. In general, masking is intended to reduce the influence of knowledge of treatment assignment on study conduct, outcome assessment, or participant reporting. The registry does not identify which parties were masked or report how masking was maintained, so those details should not be assumed.
The record includes a planning-illustration description based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it describes the effect to detect as a stated fraction of the observed effect. Those conventions describe a planning illustration, not the trial’s original design rationale or observed statistical power. The registry entries do not provide a single primary comparison for this outcome or the numerical planning outputs, and the trial’s own sample-size justification is not reported in the registry record.
For count outcomes, methods may also need to account for over-dispersion when variation exceeds what a simple model assumes. As a general explanation, over-dispersion can make standard errors too small if ignored, leading to intervals that appear more precise than warranted. The registry entries do not report the use of a count model, an over-dispersion assessment, or any other specific model for this endpoint. No particular statistical method should therefore be attributed to the trial beyond the descriptive participant counts.
Finally, the endpoint’s timeframe, “Up to Day 211,” defines the period represented by these safety observations. A count over a fixed follow-up window does not account for differences in exposure duration unless the analysis explicitly incorporates time at risk. The registry entries do not report person-time rates or a time-to-event analysis for the primary safety outcome. The outcome is consequently interpreted as participant counts over the stated period, not event rates per unit of exposure or a comparison of time until an event.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 35 outcome measures and 15 analyses, including multiple safety and antiviral outcomes. The secondary outcomes include HBV DNA viral load, HBsAg level and loss, and HBeAg loss and concentration among participants positive at baseline. Several measures are specified at Day 29 and Week 31. Considering many outcomes can raise a general statistical issue: the more separate hypotheses examined, the greater the chance that some results appear notable by chance alone. A prespecified multiplicity strategy can address that issue, but such a strategy is not reported in the registry record.
The primary safety outcome itself includes several categories or time points and is not reduced to one comparison. The registry entries do not report a family-wise error control procedure, a hierarchy of tests, or another method for interpreting multiple comparisons. The reported counts should not be mistaken for a formal multiplicity-adjusted analysis.
The registry defines the safety population as randomized participants who received at least 1 dose of GSK3228836 or placebo. The registry entries do not describe outcome-specific missing data, the number of participants with incomplete follow-up, or the methods used to handle missing observations. Those details are not reported in the registry record. No assumptions about missing outcomes or their treatment in analysis can therefore be made.
The registry entries also do not report the original sample-size justification, interim analyses, or a complete statistical analysis plan. The planning-illustration conventions described in the record do not establish what methods were prespecified for the trial. In particular, they should not be interpreted as evidence of observed power or as a justification for the number of participants enrolled.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Cohort 1 GSK3228836 150 mg | 0 | 6 | 0.0% |
| Cohort 2 and Cohort 3 GSK3228836 300 mg | 1 | 12 | 8.3% |
| Cohorts 1-3 Placebo | 0 | 6 | 0.0% |
| Cohort 4 GSK3228836 300 mg | 0 | 5 | 0.0% |
| Cohort 4 Placebo | 0 | 2 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 GSK3228836 150 mg | 0 of 6 |
| Cohort 2 and Cohort 3 GSK3228836 300 mg | 0 of 12 |
| Cohorts 1-3 Placebo | 0 of 6 |
| Cohort 4 GSK3228836 300 mg | 0 of 5 |
| Cohort 4 Placebo | 0 of 2 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cohort 1 GSK3228836 150 mg | 5 of 6 |
| Cohort 2 and Cohort 3 GSK3228836 300 mg | 6 of 12 |
| Cohorts 1-3 Placebo | 2 of 6 |
| Cohort 4 GSK3228836 300 mg | 3 of 5 |
| Cohort 4 Placebo | 0 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 GSK3228836 150 mg | Cohort 2 and Cohort 3 GSK3228836 300 mg | Cohorts 1-3 Placebo | Cohort 4 GSK3228836 300 mg | Cohort 4 Placebo |
|---|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | 0 of 6 | 1 of 12 | 0 of 6 | 0 of 5 | 0 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 GSK3228836 150 mg | Cohort 2 and Cohort 3 GSK3228836 300 mg | Cohorts 1-3 Placebo | Cohort 4 GSK3228836 300 mg | Cohort 4 Placebo |
|---|---|---|---|---|---|---|
| Pyrexia | General disorders | 1 of 6 | 3 of 12 | 1 of 6 | 1 of 5 | 0 of 2 |
| Injection site erythema | General disorders | 0 of 6 | 3 of 12 | 0 of 6 | 1 of 5 | 0 of 2 |
| Nausea | Gastrointestinal disorders | 1 of 6 | 2 of 12 | 1 of 6 | 0 of 5 | 0 of 2 |
| Injection site pruritus | General disorders | 2 of 6 | 1 of 12 | 0 of 6 | 0 of 5 | 0 of 2 |
| Injection site swelling | General disorders | 0 of 6 | 2 of 12 | 0 of 6 | 1 of 5 | 0 of 2 |
| Headache | Nervous system disorders | 0 of 6 | 2 of 12 | 1 of 6 | 0 of 5 | 0 of 2 |
| Injection site bruising | General disorders | 1 of 6 | 0 of 12 | 0 of 6 | 1 of 5 | 0 of 2 |
| Injection site pain | General disorders | 1 of 6 | 1 of 12 | 0 of 6 | 0 of 5 | 0 of 2 |
| Anaemia | Blood and lymphatic system disorders | 1 of 6 | 1 of 12 | 0 of 6 | 0 of 5 | 0 of 2 |
| Myalgia | Musculoskeletal and connective tissue disorders | 0 of 6 | 2 of 12 | 0 of 6 | 0 of 5 | 0 of 2 |
Serious events with the highest arm-level rate: alanine aminotransferase increased (8.3%).
The serious adverse event counts are 0 of 6 in Cohort 1 at 150 mg, 1 of 12 in the combined Cohort 2 and Cohort 3 group at 300 mg, 0 of 6 in the placebo groups from Cohorts 1–3, 0 of 5 in Cohort 4 at 300 mg, and 0 of 2 in the Cohort 4 placebo group. The registry reports zero deaths in each of these groups.
These are participant counts in the defined safety population, through Day 211. They describe how many participants were recorded with a serious adverse event, not the number of all serious-event episodes. The listed groups have different sizes, and the combined Cohort 2 and Cohort 3 group reflects the registry’s stated cohort handling. The counts do not establish causation or provide a precise comparative estimate.
For non-serious adverse events meeting the at-least-5% threshold, the posted affected counts are 5 of 6 in Cohort 1, 6 of 12 in the combined Cohort 2 and Cohort 3 group, 2 of 6 in the Cohorts 1–3 placebo group, 3 of 5 in Cohort 4, and 0 of 2 in the Cohort 4 placebo group. These counts concern the qualifying non-serious category and should not be confused with serious events.
The registry lists “Alanine aminotransferase increased” as a top serious-event term at 8.3%. Its group attribution and additional clinical details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry recorded serious and qualifying non-serious adverse-event counts across the listed dose cohorts and placebo groups. They also show that the group sizes were limited and differed across cohorts. One serious adverse event was recorded in the combined Cohort 2 and Cohort 3 group; no serious events were recorded in the other listed groups. Non-serious event counts were recorded in several groups, while the Cohort 4 placebo group had none under the stated threshold. No deaths were recorded.
Those observations do not establish whether an event was caused by the investigational drug. The registry’s definition includes events whether or not considered related to the investigational product. Nor do the counts establish that one group had a higher underlying risk than another: group sizes are small, dose cohorts are distinct, and no single comparative estimate or confidence interval for the primary outcome is reported in the registry record.
The endpoint is a safety measure, not a direct test of antiviral activity. Although the registry lists secondary outcomes involving HBV DNA, HBsAg, and HBeAg, their numerical results are not included in the registry record. No conclusion about those marker outcomes can be drawn from the safety counts.
As a general statistical principle, absence of an observed event in a group is not proof that the event is impossible, particularly when few participants are observed. Similarly, a nonzero count does not by itself indicate that the event is common in a broader population or that the treatment caused it. The counts are best treated as a description of events recorded in this trial’s stated safety population and follow-up period.
The record’s primary endpoint should therefore be interpreted narrowly: it reports how many participants met specified adverse-event categories through Day 211. It does not provide a complete account of event timing, duration, recurrence, resolution, or treatment attribution. It also does not furnish a definitive comparative safety estimate. Broader claims about effects, risks outside the study groups, or longer-term outcomes are not supported by these registry entries.
13. Why This Trial Matters Statistically
This trial illustrates a common statistical challenge in early clinical research: describing safety across several dose cohorts when participant groups are small. Participant counts are straightforward to understand, but they can be difficult to compare precisely when denominators differ and event numbers are limited. A zero count is informative as an observation in the trial, yet it cannot establish that the underlying event risk is zero.
The cohort structure adds an interpretive consideration. The registry records a sponsor decision that Cohort 3 received 300 mg rather than 450 mg and combines Cohorts 2 and 3 for the primary safety population. Cohort 4 is separately represented at 300 mg, alongside its placebo group. Reading the results requires attention to those group definitions rather than treating all active-treatment participants as one uniform category.
The outcome also distinguishes serious events from non-serious events meeting a stated frequency threshold. This separation makes clear that the registry is not reporting one undifferentiated safety count. At the same time, counts alone do not quantify comparative precision, explain event attribution, or capture event timing. Those limitations show why descriptive safety reporting and inferential comparison answer different questions.
More broadly, the registry lists numerous safety and antiviral outcomes, with measurements at different time points. That breadth makes transparent reporting of analysis plans, missing data, and multiplicity methods important for interpretation. Those details are not reported in the registry record. The example demonstrates why readers should distinguish registered outcomes from available numerical results and should not infer a statistical plan from a list of endpoints alone.
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 principal limitation is the small size of the safety groups: the posted denominators range from 2 to 12 participants. With counts this limited, the observed results provide little precision for comparing event occurrence across groups. No comparative estimate or confidence interval for a single primary safety contrast is reported in the registry record.
The outcome is presented across several cohort and placebo groupings, and Cohort 2 and Cohort 3 are combined for the safety population. The registry records a sponsor decision to administer 300 mg to Cohort 3 instead of 450 mg. These details limit interpretation as a simple dose-response sequence. The reasons for the decision beyond the stated sponsor decision are not reported in the registry record.
The serious-event term “Alanine aminotransferase increased” is listed at 8.3%, but its group attribution and further event details are not reported in the registry record. The registry entries do not provide event-level timing, duration, recurrence, resolution, or treatment attribution. They also do not describe whether participants could contribute to multiple categories.
Outcome-specific missingness, follow-up completeness, and handling of missing data are not reported in the registry record. Neither are the original sample-size justification, interim analyses, or a full statistical analysis plan. Although secondary antiviral outcomes are listed, their numerical results are not part of the registry entries, preventing their interpretation alongside the safety findings.
Finally, the registry’s broad adverse-event definition includes events whether or not considered related to treatment. The posted counts are therefore not counts of events judged to have been caused by the investigational drug. The registry record does not provide enough information in the registry record to resolve causal attribution or to generalize the observed counts beyond the trial population and follow-up period.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability, Pharmacokinetics and Antiviral Activity of IONIS-HBVRx in Treatment-Naïve Patients With Chronic HBV Infection — NCT02981602.
- Registry record last updated 2021-08-10; status last verified 2021-08.
- Results first posted 2020-12-21.
- 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.
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18. Record Summary
NCT02981602 is a completed Phase 2 randomized, triple-masked, parallel-group, placebo-controlled, dose-escalation study in treatment-naïve patients with chronic HBV infection. Enrollment was 31. GlaxoSmithKline is listed as sponsor; the record gives a start date of 2017-02-24 and a primary completion date of 2019-12-18.
The primary outcome counts participants with serious adverse events and non-serious adverse events meeting the at-least-5% threshold through Day 211. The safety population includes randomized participants who received at least 1 dose. Counts are reported by dose cohort and placebo group; Cohorts 2 and 3 are combined in the stated safety population, and Cohort 3 received 300 mg rather than 450 mg by sponsor decision.
The registry lists 35 outcome measures and 15 analyses, including secondary HBV DNA, HBsAg, and HBeAg outcomes. The numerical results for those secondary measures, a single comparative estimate for the primary safety outcome, and the trial’s original sample-size justification are not reported in the registry record.