An Extension Study of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Extension Study of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus (NCT03407482), a na phase 2 study. The primary outcome is Percentage of Participants With Adverse Events (AEs).

2. Clinical Question

The study was designed to evaluate long-term safety and efficacy in participants continuing into an extension after the parent study. Its primary outcome was safety-focused: the percentage of participants with adverse events. Adverse events were defined broadly and did not have to be caused by the study drug. The primary outcome therefore concerns events occurring during the stated observation period, not only events judged treatment-related.

The record also lists secondary outcomes, including the SRI-4 response measure through Week 48 and pharmacokinetic measures of GDC-0853 at steady state. However, outcome results for these measures are not reported in the registry record. The record likewise does not report a treatment comparison or an analysis estimating what would have happened without GDC-0853. The central question that can be addressed from the posted information is therefore descriptive: what adverse-event information was recorded for this extension cohort, and what can—and cannot—be concluded from a single-group safety summary?

3. Trial Design

This was a Phase II, multicenter, open-label extension study. It had a single-group model, with no masking and no randomized allocation. Participants had previously enrolled in Study GA30044 and received GDC-0853 200mg orally twice daily in the extension. The record lists an enrollment of 160.

The study was intended to evaluate long-term safety and efficacy in participants with moderate to severe active systemic lupus erythematosus who had completed the parent study. Its brief description states that the extension would follow participants for up to 48 weeks. The primary safety outcome uses a broader observation window: baseline through 8 weeks after the last dose, up to 56 weeks. These are the timeframes stated for different purposes in the registry record.

Because this was an open-label, single-group extension, participants and study personnel were not masked to treatment, and there was no concurrent comparator arm. Thus, the design can describe outcomes observed among participants who entered and received study drug, but it cannot by itself distinguish events associated with treatment from events due to the underlying condition, other factors, or the passage of time.

The record gives a start date of 2018-01-09 and a primary completion date of 2019-11-20. Its status is terminated. The reason for termination and the timing or circumstances of the termination are not reported in the registry record. Detailed information about eligibility criteria, visit schedules, treatment interruptions, adherence, and the specific operational features of the extension is not reported in the registry record either. The record describes a planned extension period, but does not establish that every participant completed that period.

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: 160 participants were enrolled into this OLE study and were included in the ITT and Safety populations.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety-evaluable population was defined as all participants who received at least one dose of the study drug during this OLE study.

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 Percentage of Participants With Adverse Events (AEs), measured over Baseline up until 8 weeks after the last dose of study drug (up to 56 weeks).

The primary endpoint is the percentage of participants with adverse events, assessed from baseline until 8 weeks after the last dose of study drug, for up to 56 weeks. The safety-evaluable population includes participants who received at least one dose during the extension. The registry definition of an adverse event is broad: it includes an untoward medical occurrence in a participant given a pharmaceutical product, whether or not the event is considered related to that product. It may include an unfavorable sign, symptom, disease, abnormal laboratory value, or abnormal clinical test result. A preexisting condition that worsens during the study also counts as an adverse event.

In general, reporting the percentage of participants with an event offers a participant-level summary of how often an event occurred in the observed cohort. It is useful for describing safety experience over a specified period, but it does not establish causation. An event counted under this definition is not necessarily a drug-related event. Interpretation also depends on the observation window, the population included, and completeness of follow-up. Those details matter especially in an extension study, where participants come from a parent trial and there is no concurrent control group.

The registry record lists 160 participants at risk for the reported safety summaries. It does not report an endpoint estimate with a confidence interval or a statistical comparison. The posted counts therefore support a descriptive reading rather than a precise estimate of comparative risk.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant percentage describe?

The primary outcome is expressed as a percentage of participants with adverse events. In general, a participant-level percentage answers how commonly at least one event was recorded in the defined population over the observation period. It differs from an event count: one participant may experience more than one event, while a participant-level measure ordinarily counts whether that participant experienced an event. The registry’s safety summary reports counts of affected participants, but does not provide a confidence interval or a statistical analysis for the primary endpoint.

In general, a confidence interval describes the statistical uncertainty around an estimated quantity under a specified method and assumptions. A narrow interval would indicate greater precision than a wide interval, but either interval would still describe uncertainty in the estimate rather than remove biases in study design or data collection. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be assessed from the posted information.

Why does the single-group design matter?

In general, a single-group study can describe what happened among participants receiving the intervention, but cannot provide a direct treatment contrast. A randomized control group can help distinguish treatment-related differences from background events and other changes over time. This extension had no comparator group, no randomized allocation, and no masking. Consequently, the reported event counts are observations in the treated cohort, not estimates of the difference between treatment and control.

Open-label status can also affect event recognition and reporting in general. Knowledge of treatment may influence how participants report symptoms or how study personnel evaluate them. That possibility does not show that reporting was biased in this study; the registry record does not report whether or how such effects were assessed. Likewise, no adjustment methods or covariates are described in the registry record.

What does the observation window contribute?

The stated primary endpoint window runs from baseline through 8 weeks after the last dose, up to 56 weeks. In general, a defined window makes clear which events are eligible for an endpoint, but interpretation depends on how long each participant was observed and whether follow-up was complete. A maximum window does not mean that every participant was followed for that length of time. Participant-specific follow-up durations and completeness are not reported in the registry record.

The primary endpoint includes adverse events whether or not considered related to the study drug. This broad definition is useful for safety surveillance because it avoids restricting collection only to events already judged drug-related. It also means that event counts should not be interpreted as counts of reactions caused by the drug. The registry record does not report separate primary endpoint estimates by causal attribution.

How should counts and event terms be read?

The safety summary lists 160 participants at risk, 4 participants with serious adverse events, 31 with other adverse events, and 0 deaths. It also names serious-event terms and reports 0.6% for each of five terms. The terms are a descriptive listing; the record does not report a comparative test of their frequencies. A reported term does not by itself provide information about severity beyond the serious-event categorization, duration, outcome, recurrence, relatedness, or whether one participant had more than one event. Those details are not reported in the registry record.

In general, rare event percentages can be difficult to estimate precisely when the number of affected participants is small. A point estimate alone does not communicate the range of values compatible with the observed data. No uncertainty interval is reported for the serious-event terms. The reported 0.6% values should therefore be read as registry percentages, not as evidence of a precise underlying event rate.

What statistical analysis is documented?

The registry record lists no analyses for the outcomes. It does not report a statistical model, hypothesis test, confidence interval method, covariate adjustment, or handling of repeated events. The analysis plan, including any prespecified statistical methods, is not reported in the registry record. As a result, the posted findings should be treated as descriptive rather than as inferential estimates from a documented analysis.

In general, statistical methods should match the outcome and design. A binary endpoint such as whether a participant had an event can be summarized with counts and percentages. If event rates were compared between groups, methods would need to account for the comparison and its assumptions. A single-group extension does not supply that between-group contrast. Over-dispersion is a general concern when count data vary more than a simple model assumes, but the registry record does not describe a count model or an analysis for recurrent events, so no such adjustment can be evaluated.

The registry also includes a sample-size planning illustration based on assumptions for a two-arm comparison. Such an illustration is hypothetical planning information, not an observed result or the original design justification for this single-group extension. The assumptions and any planning output do not establish observed power. The record’s own sample-size justification is not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("GDC-0853 (200mg) BID")
n      <- c(160)
events <- c(103)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  GDC-0853 (200mg) BID  160  103  64.4  56.4  71.8  56.7  71.4  56.7  71.4

11. Multiplicity, Missing Data and Analysis Populations

The record lists one primary safety outcome and several secondary outcomes: SRI-4 through Week 48, area under the concentration-time curve at steady state, minimum plasma concentration at steady state, plasma decay half-life at steady state, and apparent oral clearance at steady state. It does not report results for these secondary measures. The registry record does not describe a multiplicity strategy, such as a hierarchy among outcomes or an adjustment for multiple statistical tests. Because no outcome analyses are listed, the effect of multiplicity on any inferential claims cannot be assessed.

Missing-data procedures are not reported in the registry record. In particular, the record does not describe how participants with incomplete follow-up, missing endpoint assessments, treatment discontinuation, or unavailable laboratory measurements were handled. It does not report imputation, censoring rules, sensitivity analyses, or reasons for missing observations. The fact that the safety-evaluable population required at least one dose identifies who could enter that population, but does not establish how missing data within that population were handled.

The record defines the safety-evaluable population as all participants who received at least one dose during the extension. It lists 160 participants at risk in the safety summary. Other analysis populations, including populations used for the secondary outcomes, are not reported in the registry record. It is also not reported whether all enrolled participants received a dose or how many completed the planned follow-up. These limitations matter because analysis populations and missingness can affect which participants and events contribute to a reported summary.

In general, multiplicity concerns arise when many outcomes or tests are examined: the chance of at least one apparently notable finding may increase if results are interpreted without accounting for the number of comparisons. Missing-data methods address incomplete observations, but their validity depends on assumptions about why data are missing. Neither the relevant analysis choices nor their assumptions are documented in the registry record.

12. 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: cellulitis (0.6%), infective tenosynovitis (0.6%), urinary tract infection (0.6%), lumbar vertebral fracture (0.6%), systemic lupus erythematosus (0.6%).

The serious-adverse-event summary lists 4 affected participants among 160 at risk. The summary separately lists 31 participants with other adverse events and 0 deaths. These are counts in the GDC-0853 200mg twice-daily group. The registry also reports five serious-event terms, each at 0.6%: CELLULITIS, INFECTIVE TENOSYNOVITIS, URINARY TRACT INFECTION, LUMBAR VERTEBRAL FRACTURE, and SYSTEMIC LUPUS ERYTHEMATOSUS.

In general, a serious adverse event is a seriousness classification, not a statement that the study drug caused the event. The primary endpoint definition explicitly includes occurrences that are not considered related to treatment. The record does not report the relationship of these events to GDC-0853, individual event narratives, outcomes, or whether participants experienced multiple terms. The term percentages should therefore be read as descriptive entries, not as comparative estimates.

Because the extension had no control group, the counts cannot establish whether serious events occurred more or less often than they would have under another treatment or without study drug. The record also does not report confidence intervals for the counts or term percentages. The 0 deaths listed is the result in the posted safety summary, not proof that the treatment has no risk of death or that no unreported event occurred.

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

The posted results describe safety events observed in a single group of participants who received GDC-0853 200mg twice daily in an open-label extension. They include 4 participants listed with serious adverse events, 31 with other adverse events, and 0 deaths among 160 participants at risk. The serious-event terms and their reported percentages add descriptive detail, but do not provide a treatment comparison.

These observations do not show that GDC-0853 caused the listed events. The adverse-event definition includes occurrences that do not necessarily have a causal relationship with treatment, and the record does not provide event-specific causality assessments. Conversely, the counts cannot establish that treatment was free of risk. They describe what the registry summary reports for this cohort and observation window.

The results also do not establish efficacy. SRI-4 is listed as a secondary outcome, but its results are not reported in the registry record. Pharmacokinetic measures are listed as secondary outcomes as well, but results are not reported. No comparison with a control group, change from baseline, or statistical analysis of these outcomes is documented.

In general, a single-group extension is suited to describing experience among participants who enter and receive treatment, while offering limited evidence about what would have happened under an alternative. The cohort consisted of participants previously enrolled in and completing the parent study, and the registry record does not give enough information to characterize selection into the extension or the completeness of follow-up. The terminated status is reported, but its reason is not reported in the registry record. Thus, the findings should be understood as limited descriptive safety information, not a causal estimate, a comparative safety conclusion, or a demonstration of benefit.

14. Why This Trial Matters Statistically

This study illustrates a common statistical distinction: an observed event count is not the same as an estimate of treatment effect. The extension records safety experience in participants receiving GDC-0853, but its single-group, open-label design supplies no concurrent comparator. The reported counts are informative as descriptions of the cohort, while leaving unanswered whether the observed events differ from what might occur in another group.

The endpoint definition also matters. Adverse events include medical occurrences that need not be caused by treatment, and the primary summary covers a specified period extending beyond the last dose. A reader must therefore consider both the broad event definition and the observation window when interpreting what the endpoint captures. The distinction between serious and other adverse events provides another descriptive layer, but does not establish causation or comparative risk.

The study’s extension setting is relevant to interpretation because participants had previously been enrolled in and completed the parent study. This defines the population being described and means the results should not automatically be generalized to all people with systemic lupus erythematosus. The registry record does not report enough detail to quantify how this selection affects the observed safety experience.

Finally, the record demonstrates why results and analysis documentation matter. Secondary outcomes are named, but their results are not reported, and no outcome analyses are listed. Without estimates, uncertainty measures, and a documented analysis plan, a reader cannot assess the precision of the findings or evaluate inferential claims. The most defensible statistical reading is therefore appropriately narrow: the registry reports descriptive safety counts for this extension cohort, with important comparative and analytic questions unanswered.

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 principal design limitation is the absence of a control group. With one treatment group and no randomization, the study cannot estimate a treatment contrast or separate treatment effects from the background occurrence of events. Open-label conduct also means treatment was not masked; the registry record does not report whether possible effects of treatment awareness on reporting or assessment were evaluated.

The cohort was drawn from participants previously enrolled in and completing Study GA30044. The registry record does not report how many parent-study participants were eligible for the extension, how entry was determined, or how participants who did not enter differed from those who did. This limits assessment of selection and generalizability. The record lists 160 enrolled and 160 at risk in the safety summary, but does not report participant-level follow-up duration, completion, or discontinuation information.

The study is marked terminated, but the reason for termination is not reported in the registry record. The record does not report the number or timing of treatment interruptions, the completeness of adverse-event ascertainment, event-relatedness assessments, or individual event outcomes. No confidence intervals, statistical analyses, missing-data procedures, or multiplicity plan are listed. Secondary outcome results are not reported in the registry record.

These gaps prevent assessment of precision, robustness, and the impact of incomplete observations. They also mean the safety counts cannot be interpreted as evidence of comparative risk, and the record does not support conclusions about efficacy. The available findings are best treated as descriptive information from a specific extension cohort, with the stated design and reporting limitations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Extension Study of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus — NCT03407482.
• Registry record last updated 2020-12-19; status last verified 2020-11.
• Results first posted 2020-12-19.
• 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

NCT03407482 is a Phase II, multicenter, open-label extension study of GDC-0853 in participants with moderate to severe active systemic lupus erythematosus who had previously completed Study GA30044. The single-group study had no masking or randomized allocation. The extension regimen was GDC-0853 200mg orally twice daily, and enrollment was 160.

The primary outcome was the percentage of participants with adverse events from baseline through 8 weeks after the last dose, up to 56 weeks. The registry safety summary lists 4 participants with serious adverse events, 31 with other adverse events, and 0 deaths among 160 at risk. Five serious-event terms are listed, each at 0.6%.

The study status is terminated. Results for the listed secondary outcomes, the reason for termination, statistical analyses, and methods for missing data are not reported in the registry record. The single-group design supports descriptive interpretation, not a causal or comparative treatment conclusion.