A Study of the Safety and Efficacy 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 A Study of the Safety and Efficacy of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus (NCT02908100), a randomized phase 2 study. The primary outcome is Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48.

2. Clinical Question

The trial assessed a composite response rather than a single symptom or laboratory measure. SRI-4 combines changes in disease activity scores with limits on new disease activity and worsening in a physician assessment. The central comparison is therefore between the percentage meeting all response criteria in each randomized group, not a comparison of average change in one component.

The clinical question also concerns GDC-0853 as an addition to standard of care, rather than as a replacement for background treatment. The registry record describes a randomized, parallel-group comparison and reports results for placebo and both active regimens. It does not report the original sample-size justification or the detailed protocol for handling missing endpoint data.

3. Trial Design

This was a Phase II, randomized, double-blind, placebo-controlled, parallel-group study. The registry record lists enrollment of 260 participants and describes the study as completed. The recorded study start was 2017-01-19, and primary completion was 2019-05-28.

Three groups were compared: matching placebo, GDC-0853 (150mg) QD, and GDC-0853 (200mg) BID. Each regimen was taken orally from Day 1 through Week 48 alongside background standard of care therapy. The randomized structure supports comparisons between assigned groups; double blinding means that the study was described as masked for participants and investigators, although further details about who was masked are not reported in the registry record.

The primary outcome was the percentage of participants with an SRI-4 response at Week 48. The primary analysis population was the intent-to-treat population, defined as all randomized participants regardless of whether they received study drug. The listed group sizes for this outcome were 86 for placebo and 87 in each active group.

The registry record lists 10 outcome measures and 32 analyses. It does not report the original design assumptions for the trial’s sample size, the full statistical analysis plan, or whether interim analyses were planned or conducted. The sample-size illustrations associated with the posted results use observed effects and are distinct from the trial’s original design rationale.

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: An overall total of 616 participants were screened into the study, of which 356 participants were screen failures. 260 participants (Intent-To-Treat/ITT population) were randomized into the study, of which 1 participant did not receive any study treatment meaning that the Safety population consisted of 259 participants.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Intent-To-Treat (ITT) population was defined as all randomized participants regardless of whether they received any study drug.

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 Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48, measured over Week 48.

The primary endpoint was the percentage of participants with a Systemic Lupus Erythematosus Responder Index (SRI)-4 response at Week 48. SRI-4 is a composite measure intended to capture improvement in SLE disease activity while also requiring that improvement is not accompanied by specified worsening on other assessments.

A response requires a reduction of at least 4 points from baseline in the SLEDAI-2K score, no new BILAG A disease activity score and no more than 1 new BILAG B score, and no worsening in the Physician’s Global Assessment. Worsening in that assessment is defined as an increase of at least 0.3 points [10 mm] from baseline. The registry record describes the SLEDAI-2K score range as 0 to 100, with higher scores indicating greater disease activity.

Using a composite endpoint can be useful when a condition has multiple clinical dimensions. Requiring improvement on one measure while limiting deterioration on others makes the response definition broader than a change in a single score. At the same time, a participant must satisfy the component criteria together to count as a responder. The endpoint therefore summarizes a particular pattern of change; it does not describe every aspect of disease activity or establish the effect on each component separately.

The primary measure is reported as a percentage of participants, so the result represents the proportion in each group meeting the response definition by Week 48. It does not, by itself, explain the experience of participants who did not meet the full composite criteria.

7. Results Posted in the Registry

• GDC-0853 (150mg) QD: 50.6% (44/87) versus 44.2% (38/86) on control; risk difference 6.4 percentage points (95% CI -8.5 to 21.2), risk ratio 1.14 (0.83–1.57); unadjusted two-proportion z-test p = 0.400.
• GDC-0853 (200mg) BID: 51.7% (45/87) versus 44.2% (38/86) on control; risk difference 7.5 percentage points (95% CI -7.3 to 22.4), risk ratio 1.17 (0.86–1.60); unadjusted two-proportion z-test p = 0.321.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams Per Day (mg/Day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • GDC-0853 (150mg) QD: 50.6% (44/87) versus 41.9% (36/86) on control; risk difference 8.7 percentage points (95% CI -6.1 to 23.5), risk ratio 1.21 (0.87–1.67); unadjusted two-proportion z-test p = 0.250.
  • GDC-0853 (200mg) BID: 44.8% (39/87) versus 41.9% (36/86) on control; risk difference 3.0 percentage points (95% CI -11.8 to 17.7), risk ratio 1.07 (0.76–1.51); unadjusted two-proportion z-test p = 0.694.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between GDC-0853 (150mg) QD and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between GDC-0853 (200mg) BID and the control. The interval gives the range of effects that remain compatible with the data.

SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/Day and </= Day 1 Dose During Week 12 Through Week 24

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • GDC-0853 (150mg) QD: 47.1% (41/87) versus 43.0% (37/86) on control; risk difference 4.1 percentage points (95% CI -10.7 to 18.9), risk ratio 1.10 (0.79–1.52); unadjusted two-proportion z-test p = 0.588.
  • GDC-0853 (200mg) BID: 47.1% (41/87) versus 43.0% (37/86) on control; risk difference 4.1 percentage points (95% CI -10.7 to 18.9), risk ratio 1.10 (0.79–1.52); unadjusted two-proportion z-test p = 0.588.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between GDC-0853 (150mg) QD and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between GDC-0853 (200mg) BID and the control. The interval gives the range of effects that remain compatible with the data.

SRI-4 Response at Week 24

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • GDC-0853 (150mg) QD: 52.9% (46/87) versus 46.5% (40/86) on control; risk difference 6.4 percentage points (95% CI -8.5 to 21.2), risk ratio 1.14 (0.84–1.54); unadjusted two-proportion z-test p = 0.403.
  • GDC-0853 (200mg) BID: 52.9% (46/87) versus 46.5% (40/86) on control; risk difference 6.4 percentage points (95% CI -8.5 to 21.2), risk ratio 1.14 (0.84–1.54); unadjusted two-proportion z-test p = 0.403.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between GDC-0853 (150mg) QD and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between GDC-0853 (200mg) BID and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering SRI-4 responses at different time points, response with sustained oral corticosteroid reduction, response across plasmablast signature groups, SRI-6, BICLA, and adverse events. The secondary outcomes therefore examine related but non-identical aspects of response, treatment context, subgroup patterns, and safety. They are not interchangeable with the Week 48 primary endpoint.

Among the secondary results with numerical comparisons reported, the response percentages in active groups are generally numerically higher than placebo, but the reported confidence intervals include zero. This broad pattern is compatible with the primary result: the observed proportions tend to favor active groups, while the estimates remain uncertain. It does not establish that each secondary measure has the same underlying effect or that any observed numerical ordering is conclusive.

Secondary outcomes often help describe whether the primary pattern is echoed across related measures and time points. Differences in endpoint definition, assessment time, and requirements for sustained corticosteroid reduction can produce different response proportions. A result on one secondary measure should therefore be interpreted according to that measure’s own definition rather than treated as a direct replication of the primary endpoint.

The registry reports 10 outcome measures and 32 analyses. Multiple outcomes and comparisons raise the possibility of chance findings when many hypotheses are examined. Unless an analysis plan accounts for this multiplicity, nominal p-values from secondary comparisons generally carry less evidential weight than a prespecified primary analysis. The multiplicity procedure and a hierarchy for interpreting these outcomes are not reported in the registry record. Secondary findings should consequently be viewed as supporting context, not as stand-alone proof.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams Per Day (mg/Day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48
• SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/Day and </= Day 1 Dose During Week 12 Through Week 24
• SRI-4 Response at Week 24
• SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels
• SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels
• SRI-6 Response at Week 24 and 48
• BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48
• Percentage of Participants With Adverse Events (AEs)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either meets the SRI-4 response definition at Week 48 or does not. The registry reports the percentage meeting the definition in each group. For a binary outcome, a difference in percentages is commonly expressed as an absolute risk difference, also called an absolute difference in response proportions. A positive difference means the observed response proportion is higher in the active group than in the comparator group; it does not, on its own, establish that the difference is precise or statistically persuasive.

What does the reported comparison estimate?

The sponsor reported absolute differences for each GDC-0853 group compared with placebo, along with 95% confidence intervals and p-values. The reported differences are in percentage points. The 150mg QD comparison was 6.4 percentage points, with a 95% confidence interval from -8.5 to 21.2. The 200mg BID comparison was 7.5 percentage points, with a 95% confidence interval from -7.3 to 22.4.

A confidence interval gives a range of estimates that are reasonably compatible with the data under the statistical procedure used. It describes uncertainty in the estimated contrast; it is not a range containing a stated percentage of individual participants’ outcomes, nor is it a probability interval for the true effect after the data have been observed. Because each reported interval crosses zero, the results do not rule out no difference under these intervals. Their width also indicates that the magnitude is uncertain.

What is the Cochran-Mantel-Haenszel method?

The registry identifies the sponsor’s method as Cochran-Mantel-Haenszel. In general, this method is used to compare categorical outcomes across groups while accounting for strata. The registry record does not report the strata used for these analyses or further details of the implementation. Consequently, the reported sponsor estimates should be interpreted as the registry’s stated analyses, without assuming additional details about stratification or covariate adjustment.

The posted recalculations use the response counts and group sizes to form simple, unadjusted comparisons. In general, an unadjusted analysis compares groups without incorporating additional stratification or covariates. Such recalculations can be useful for understanding the scale and approximate uncertainty of a contrast, but they are not a substitute for the sponsor’s prespecified analysis. No discrepancy is flagged between the posted recalculations and the sponsor results.

How should p-values be understood?

A p-value evaluates how unusual data at least as incompatible with a null hypothesis as the observed results would be if that null model held, given the analysis assumptions. Smaller p-values generally indicate greater incompatibility with that null model, but a p-value does not express the probability that a treatment effect exists. It also does not convey the size or clinical importance of a difference. The reported primary p-values are 0.373 and 0.339 for the two active-versus-placebo comparisons.

Interpretation should consider the p-values together with effect estimates and confidence intervals. Here, the confidence intervals include zero and extend to values on either side of zero. This means the data do not precisely locate the underlying difference. A p-value alone cannot resolve that uncertainty, and the record does not state a complete decision rule or adjustment plan for the multiple analyses.

Why does the analysis population matter?

The primary outcome population is described as intent-to-treat: all randomized participants, whether or not they received study drug. This definition retains participants in the group to which they were randomized and makes the estimand correspond to assignment under the trial’s randomized comparison. It does not explain how missing Week 48 measurements were treated. The handling of missing data, any imputation methods, and any sensitivity analyses are not reported in the registry record.

For general context, missing outcomes can affect both the estimated response percentages and the uncertainty around comparisons. The consequences depend on how much outcome information is absent and on the assumptions used to address it. Without the analysis details, those assumptions cannot be assessed from the registry record alone.

What does a binary endpoint leave out?

A percentage summarizes how many participants met a defined response rule, but it compresses a complex clinical assessment into a responder/non-responder classification. It does not show the distribution of changes within each group or the separate behavior of the SLEDAI-2K, BILAG, and Physician’s Global Assessment components. The endpoint’s meaning depends on its stated criteria, and interpretation should not extend beyond what that composite captures.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data estimate a group difference. For the primary outcome, the sponsor’s 95% confidence interval for GDC-0853 (150mg) QD versus placebo runs from -8.5 to 21.2 percentage points around an estimated absolute difference of 6.4 percentage points. For GDC-0853 (200mg) BID versus placebo, the estimate is 7.5 percentage points and the interval runs from -7.3 to 22.4 percentage points.

Both intervals include zero. In practical statistical terms, the posted results do not pin down whether the underlying difference is positive, absent, or negative. The estimates are numerically positive, but the confidence limits indicate that the direction and size remain uncertain. The intervals also permit differences larger than the point estimates, so the result is not precise enough to treat the observed estimates as exact effect sizes.

In general, confidence intervals become narrower when the data contain more information, while smaller samples or more variable outcomes tend to produce wider intervals. For a binary response, the amount of information depends in part on the number of participants and the response proportions. The trial’s original precision target and sample-size rationale are not reported in the registry record, so the observed interval width cannot be assessed against a stated design target.

The distinction between precision and statistical significance matters. A confidence interval that crosses zero is not evidence that the true effect is exactly zero. It means the data and method do not exclude zero at the confidence level used. Nor does an interval crossing zero establish equivalence or non-inferiority; those conclusions require specific design criteria that are not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations give participants per arm for the binary outcomes, rather than total events. They are based on the observed effect and use the stated assumptions: a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect. The original sample-size assumptions for the trial itself are not reported in the registry record.

The 80% power column represents the number of participants per arm a hypothetical future comparison would require to have an 80% chance of detecting the specified effect, under the listed planning assumptions, if that effect were the true one. The 90% power column makes the same kind of illustration with a higher target probability of detection, which generally requires more participants. These are planning quantities, not estimates of the probability that the completed trial found a real effect.

For example, the primary comparison planning for 100% of the observed effect gives 958 participants per arm for 80% power and 1,282 for 90% power for the 150mg QD contrast. For the 200mg BID contrast, the corresponding figures are 689 and 921 participants per arm. Planning for 75% of the observed effect requires 1,701 and 2,276 participants per arm for 150mg QD, and 1,223 and 1,636 for 200mg BID, at the respective power targets.

Smaller effects are harder to distinguish from random variation and therefore require more participants under otherwise similar assumptions. The figures are illustrations derived from the observed comparisons, not a reconstruction of the trial’s original design. This is not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.442; treatment proportion p₁ = 0.506; average p̄ = 0.474.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7061 = 1.3840.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7047 = 0.5931.
4. n = (1.3840 + 0.5931)² / (0.0639)² = 957.7, rounded up to 958 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.441860465116279                          # control proportion
p1 <- 0.505747126436782                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2908100)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 958 (80% power), 1,282 (90% power)
 75% of observed effect: n per arm = 1,701 (80% power), 2,276 (90% power)
 50% of observed effect: n per arm = 3,818 (80% power), 5,111 (90% power)
power.prop.test: 957.7 
Simulated power at n = 958 per arm: 0.804 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports sponsor analyses using the Cochran-Mantel-Haenszel method. For the primary SRI-4 outcome, the sponsor reported an absolute difference of 6.4 percentage points for GDC-0853 (150mg) QD versus placebo, with a 95% confidence interval from -8.5 to 21.2 and p = 0.373. For GDC-0853 (200mg) BID versus placebo, the reported absolute difference was 7.5 percentage points, with a 95% confidence interval from -7.3 to 22.4 and p = 0.339.

The recalculations are simple unadjusted comparisons based on posted summary counts and group sizes. They express risk differences on the proportion scale, while the sponsor reports absolute differences in percentage points. These are different ways of expressing the same type of contrast, but the analytical procedures are not necessarily identical. The registry record does not flag a discrepancy between the recalculations and the sponsor analysis.

For interpretation, the sponsor’s own analysis is the primary reported analysis. Its confidence intervals include zero for both active-versus-placebo comparisons. The recalculations can serve as a check on the general scale of the observed contrasts, but they should not replace the sponsor’s reported method or be treated as an independent confirmation.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures and 32 analyses, including the primary outcome, secondary outcomes, and safety measures. Each additional comparison creates another opportunity for results to appear unusual by chance. In general, when many hypotheses are tested, interpreting each p-value as if it were the only test can overstate the strength of evidence. Statistical plans can address this through methods such as a hierarchy of outcomes or multiplicity adjustment, but the registry record does not report whether either approach was used.

The primary outcome and its reported comparisons are identifiable, but the full testing strategy is not. The registry record does not report whether the secondary outcomes were confirmatory or exploratory, whether comparisons were ordered, or whether p-values were adjusted. Accordingly, the secondary p-values should not be read as if they necessarily control the overall chance of false-positive findings across all analyses.

The primary population is described as intent-to-treat, including all randomized participants regardless of whether they received study drug. That definition is useful for understanding who was intended to contribute to the primary analysis, but it does not specify how incomplete Week 48 outcomes were handled. Methods for missing data, reasons for missingness, imputation, and sensitivity analyses are not reported in the registry record.

In general, missing outcome data can complicate interpretation if the probability of having an observed result is related to response. Different assumptions about participants without an observed endpoint can lead to different estimates. The registry record does not provide enough detail to assess whether missingness could have affected the reported comparisons or how robust the results are to alternative assumptions. The same caution applies to analysis details not described in the record, including any protocol deviations and the handling of participants who discontinued treatment.

16. 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: systemic lupus erythematosus (2.4%), congestive cardiomyopathy (1.2%), multiple organ dysfunction syndrome (1.2%), epstein-barr virus infection (1.2%), gastroenteritis bacterial (1.2%).

The registry reports serious adverse event counts for participants at risk in each group. There were 9 serious adverse events among 84 participants at risk in the placebo group, 4 among 87 at risk with GDC-0853 (150mg) QD, and 12 among 88 at risk with GDC-0853 (200mg) BID. Deaths reported were 2, 1, and 0, respectively. These are descriptive counts and denominators, not adjusted comparisons between groups.

The registry also lists serious adverse event terms, including systemic lupus erythematosus at 2.4%, congestive cardiomyopathy at 1.2%, multiple organ dysfunction syndrome at 1.2%, Epstein-Barr virus infection at 1.2%, bacterial gastroenteritis at 1.2%, and infected skin ulcer at 1.2%. The listed terms should be read as coded event categories in the record; they do not by themselves establish cause or attribution.

Safety counts can be difficult to compare without further information about event definitions, duration of exposure, recurrence, severity, and how events were collected. Those details are not reported in the registry record. The counts alone do not establish whether an event was caused by a study treatment, and they should not be interpreted as a complete assessment of comparative safety.

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

The primary result describes the proportion of randomized participants meeting a defined composite SRI-4 response at Week 48. The observed percentages were 44.2% for placebo, 50.6% for GDC-0853 (150mg) QD, and 51.7% for GDC-0853 (200mg) BID. The sponsor-reported contrasts are positive in direction, but both confidence intervals include zero and the estimates are imprecise.

These results do not demonstrate that the groups had identical response rates. They also do not establish a reliable difference of a particular size. The confidence intervals leave room for no difference and for effects in either direction, while the point estimates alone do not capture that uncertainty. The record does not report a design for equivalence or non-inferiority, so the results should not be interpreted as establishing either.

The endpoint reflects a combined definition involving SLEDAI-2K, BILAG, and Physician’s Global Assessment. It does not show the separate contribution of each component, nor does it summarize every aspect of SLE. The response percentage also does not describe how each individual participant’s condition changed beyond whether the composite criteria were met.

The study compared each active regimen with placebo in the context of background standard of care. The findings therefore concern those treatment comparisons in the enrolled trial population and under the trial’s stated endpoint definition. They do not provide evidence about other regimens, populations, follow-up periods, or treatment settings not described in the registry record.

The appropriate interpretation is bounded: the posted data show numerically higher primary response percentages in both GDC-0853 groups than in placebo, alongside substantial statistical uncertainty. The registry results alone do not support a definitive claim about the presence, absence, or clinical importance of a treatment effect. They also do not replace a complete assessment of missing data, multiplicity, and safety information, several aspects of which are not reported in the registry record.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through both its point estimate and its uncertainty. The active groups had numerically higher Week 48 SRI-4 response percentages than placebo, yet the reported confidence intervals include zero and extend across a broad range of possible differences. A simple ranking of observed percentages would miss the uncertainty in the underlying comparison.

It also illustrates the importance of distinguishing an endpoint from the clinical construct it represents. SRI-4 combines several assessments and applies a specific response rule. That can provide a useful summary of response, but the single percentage does not reveal how each component behaved or how participants who did not meet every criterion changed.

The trial’s reported analyses and the unadjusted recalculations answer closely related questions but are not automatically identical procedures. Understanding the method named in the registry, the population analyzed, and the confidence interval helps avoid treating a recalculated summary as a replacement for the reported analysis.

Finally, the record lists numerous outcome measures and analyses. That makes the missing information about multiplicity and missing-data methods relevant to the strength of conclusions, particularly for secondary findings. The sample-size illustrations also demonstrate the general planning consequence of targeting smaller effects: more participants per arm are needed under the stated assumptions. Together, these features make the trial a useful case for separating observed patterns from precise and confirmatory evidence.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the original sample-size calculation or the assumptions used to design the trial. Consequently, the planned effect size, target power, and intended precision for the primary comparison cannot be assessed from the record. The planning illustrations based on observed effects are not a substitute for those original design details.

Although the primary population is defined as intent-to-treat, the registry record does not report how missing Week 48 outcomes were handled, how many participants lacked endpoint data, or whether sensitivity analyses were conducted. The primary outcome counts and group sizes are reported, but they do not provide a full account of missingness or discontinuation.

The registry identifies the sponsor method as Cochran-Mantel-Haenszel but does not report the strata or further implementation details. It also does not report whether multiplicity was controlled across the 32 analyses, or how the primary and secondary outcomes were ordered for inference. This limits assessment of the confirmatory status of secondary findings.

The study was described as double-blind, but the registry record does not give further details about masking procedures or the success of masking. The record also does not provide enough detail to assess event exposure time, recurrent adverse events, or attribution of serious adverse events. Finally, a composite endpoint cannot show from the reported overall response percentages how the component assessments individually contributed to the result.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of the Safety and Efficacy of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus — NCT02908100.
• Registry record last updated 2024-05-08; status last verified 2024-05.
• Results first posted 2020-07-07.
• 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.

23. Record Summary

The registry describes a completed, randomized, double-blind, placebo-controlled Phase II study of GDC-0853 with standard of care therapy in participants with moderate to severe active SLE. The trial enrolled 260 participants and compared placebo with GDC-0853 150mg once daily and 200mg twice daily through Week 48.

The primary outcome was SRI-4 response at Week 48 in the intent-to-treat population. Response percentages were 44.2% with placebo, 50.6% with 150mg QD, and 51.7% with 200mg BID. Sponsor-reported absolute differences versus placebo were 6.4 and 7.5 percentage points, with 95% confidence intervals that included zero.

The posted results show numerically higher response percentages in the active groups, but substantial uncertainty around the comparisons. Details of the trial’s original sample-size rationale, missing-data methods, and multiplicity procedures are not reported in the registry record.