A Study Evaluating the Effects of GLPG3970 Given as an Oral Treatment for 12 Weeks in Adults With Active Primary Sjögren's Syndrome (pSS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating the Effects of GLPG3970 Given as an Oral Treatment for 12 Weeks in Adults With Active Primary Sjögren's Syndrome (pSS) (NCT04700280), a randomized phase 2 study. The primary outcome is Change From Baseline in European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) Score at Week 12.

2. Clinical Question

3. Trial Design

This Phase 2 study was randomized, quadruple-masked, placebo-controlled, multicenter, and parallel-group. It evaluated orally administered GLPG3970 over 12 weeks in adults with active primary Sjögren's syndrome. The registry record lists 31 participants enrolled. The GLPG3970 arm received 400 mg once daily, described as 2 *200 mg tablets; the placebo arm received a matched tablet once daily. The registry lists Lakefront Biotherapeutics NV as the sponsor.

The study began on 2021-01-28 and has a primary completion date of 2021-10-28. Its status is terminated. The reason for termination is not reported in the registry record, so the status alone does not establish why the study ended or whether the planned course of the study was completed.

The primary outcome was change from baseline in ESSDAI score at Week 12. The registry also lists changes in ESSPRI and ESSDAI at Weeks 4, 8, and 12, and observed pre-dose plasma concentration of GLPG3970. The record lists five outcome measures and six analyses. It does not report the full protocol, the planned enrollment target, or a sample-size justification. The reported outcome analysis includes eight participants in the GLPG3970 arm and five in the placebo arm with available data for the primary outcome; these analysis counts are not the overall enrollment count.

Randomization and masking are design features intended to limit systematic differences in treatment assignment and assessment. The registry identifies those features, but does not report the methods used to generate the allocation sequence, maintain concealment, or implement masking. Those procedural details are not reported in the registry record.

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 69 participants were screened. Of these, 31 participants were randomized and treated in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants in the full analysis set (FAS: all randomized participants who received at least one dose of study drug) with available data were analyzed.

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: The safety analysis set included all randomized participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) Score at Week 12, measured over Baseline, Week 12.

The primary endpoint is change from baseline in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score at Week 12. ESSDAI assesses disease activity across 12 domains, including glandular, articular, pulmonary, renal, muscular, nervous-system, and biological domains. Each domain is assigned an activity level and weighted to contribute to the overall score.

The score ranges from 0, indicating the best score, to 123, indicating the worst activity; a higher score indicates more disease activity. A reduction of at least 3 points from baseline is described in the registry as a clinically meaningful reduction. This endpoint is used to summarize systemic disease activity rather than a single symptom or organ system. Measuring change from baseline focuses the comparison on how scores shifted over the study period, while the Week 12 time point gives a specified endpoint for the primary comparison.

The registry reports least-squares means from a mixed model for repeated measures. The posted arm values are changes from baseline, so negative values represent reductions in ESSDAI score. The outcome analysis covers participants in the full analysis set with available data. The record does not report all details needed to assess how missing Week 12 values were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Outcome and estimand. The endpoint is a continuous measure: change from baseline in ESSDAI score at Week 12. The analysis reports an estimated contrast between GLPG3970 and placebo. In general, an estimand is the quantity a study analysis seeks to estimate; here, the posted comparison is the difference in modeled mean change between the arms at the specified time point. The registry identifies the outcome as a least-squares mean and the comparison as a least-squares mean difference.

Least-squares means. A least-squares mean is a model-based estimate of an arm's mean outcome. It is not necessarily identical to a simple arithmetic average, because its value depends on the fitted model and the data included. The registry reports arm-level changes of -4.4 and -3.0 and an estimated difference of -1.4. The statistical model details beyond the stated method are not reported in the registry record.

Mixed models for repeated measures. The primary outcome description says least-squares means were calculated using mixed models for repeated measures (MMRM). In general, this type of model can use measurements collected at multiple visits while accounting for their correlation within a participant. Repeated observations from one participant are generally not independent, and a model can represent that relationship rather than treating each observation as unrelated. The registry lists baseline and Week 12 for the primary timeframe and other ESSDAI visits at Weeks 4, 8, and 12. It does not report the covariance structure, fixed effects, or other model specifications, so those details cannot be assessed from the registry record.

Standard error and uncertainty. The arm-level dispersion is reported as a standard error. In general, a standard error describes uncertainty around an estimated mean; it is not a measure of the spread of individual participant scores. The reported arm standard errors are 1.56 for GLPG3970 and 2.03 for placebo. The registry's comparison includes a 90% confidence interval from -6.2 to 3.4. In general, a confidence interval conveys uncertainty about the estimated contrast under the model. Its width is relevant because a point estimate alone does not show how precisely the contrast is estimated.

Interpreting the p-value. The registry reports p = 0.617 for the mixed-model analysis. In general, a p-value measures how compatible the observed data are with a specified null hypothesis under the model assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A non-small p-value is not proof of no difference; interpretation should consider the point estimate, confidence interval, study size, and analysis details together.

Direction of change. The registry defines a higher ESSDAI score as more disease activity. Therefore, a negative change indicates a reduction in score from baseline. The estimated difference is also negative, which places the point estimate in the direction of a larger reduction in the GLPG3970 arm. This direction does not resolve the uncertainty in the interval, which spans both negative and positive values.

Analysis population. The record says the full analysis set includes all randomized participants who received at least one dose of study drug, and that participants with available data were analyzed. The primary outcome counts are 8 and 5. In general, the population included in an analysis affects the interpretation of its estimate. The record does not report the number randomized to each arm, the specific missing-data method, or participant-level reasons for missing measurements. Those details are not reported in the registry record.

Multiplicity and other outcomes. The registry lists multiple outcomes and analyses, including ESSPRI, ESSDAI at several visits, and a pharmacokinetic measure. In general, when many statistical comparisons are conducted, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. The record does not report a multiplicity adjustment or a hierarchy of tests. It also does not report whether interim analyses were planned or conducted. The primary result can be described as posted, but its relationship to a broader testing strategy cannot be determined from the registry record.

Planning illustrations. Any sample-size illustrations based on the observed effect are planning exercises rather than observed trial outcomes. In general, such illustrations depend on their assumptions and should not be interpreted as observed power or as evidence that the study was designed to detect a particular effect. The trial's own sample-size justification is not reported in the registry record.

10. Confidence Intervals for Each Arm

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

R code and output

arm <- c("GLPG3970", "Placebo")
n   <- c(8, 5)
m   <- c(-4.4, -3)
sp  <- c(1.56, 2.03)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  GLPG3970  8  -4.400  4.412  -8.089  -0.711
CARM  Placebo  5  -3.000  4.539  -8.636  2.636

11. Analyses Reported by the Sponsor

The registry's reported primary analysis is the sponsor's mixed-model comparison: a least-squares mean difference of -1.4, with a 90% confidence interval from -6.2 to 3.4 and p = 0.617. The arm-level changes are -4.4 for GLPG3970 and -3.0 for placebo. The reported comparison, rather than an informal subtraction of arm summaries, is the relevant posted estimate because it comes from the stated mixed-model analysis.

The record does not identify a separate recalculated comparison for this endpoint. The arm-level summaries include standard errors, but a new unadjusted calculation would not reproduce the stated model-based analysis. No discrepancy is indicated in the record. The interpretation should therefore center on the sponsor's reported analysis, including its uncertainty, rather than treating the arm summaries as a replacement for that analysis.

The registry does not provide enough model details to independently evaluate the specification or reproduce the sponsor's result. The comparison is reported with its estimate, confidence interval, and p-value, but additional details such as covariate terms and the repeated-measures covariance structure are not reported in the registry record.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes: the primary Week 12 ESSDAI change, ESSPRI change at Weeks 4, 8, and 12, ESSDAI change at Weeks 4, 8, and 12, and observed pre-dose plasma concentration of GLPG3970. It also reports five outcome measures and six analyses. These results address different questions and time points; they should not automatically be treated as independent confirmations of a single finding.

In general, testing several outcomes or time points can increase the chance that at least one result appears notable by chance. A prespecified testing hierarchy or multiplicity adjustment can address that concern, but whether either was used is not reported in the registry record. The registry record also does not report a complete statistical analysis plan, so the planned role of secondary outcomes and the precise primary testing strategy cannot be established.

For the primary outcome, the record describes the full analysis set as randomized participants who received at least one dose, with available data analyzed. It does not report the number of participants with missing Week 12 ESSDAI values, reasons for missingness, or a detailed method for handling missing outcomes. Although MMRM is named, the record does not specify its assumptions about missing data or the steps used to examine their impact.

These omissions matter because the interpretation of a model-based estimate depends on which participants contributed information and how incomplete measurements were handled. The outcome analysis counts—8 in the GLPG3970 arm and 5 in the placebo arm—are smaller than the overall enrollment count, but the record does not explain the difference. The reason for the study's terminated status is also not reported in the registry record. No interim analyses or sample-size justification are reported, and neither should be inferred from the posted results.

13. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: drug-induced liver injury (5.0%), liver injury (5.0%).

The safety counts use different denominators from the primary-outcome analysis. The registry reports 20 participants at risk in the GLPG3970 group and 11 in the placebo group for serious adverse events. Serious adverse events affected 2 participants in the GLPG3970 group and 0 in the placebo group. The record reports 0 deaths in each group.

For other adverse events, 10 of 20 participants in the GLPG3970 group and 7 of 11 in the placebo group were affected. The registry lists “Drug-induced liver injury” and “Liver injury” among the top serious terms, each at 5.0%. These terms should be read as the registry's reported event labels; the record does not establish that the events were caused by study treatment. It also does not report participant-level details, timing, duration, or outcome for these events.

Adverse-event counts are descriptive safety information, not a randomized efficacy comparison. The different group sizes and the limited number of participants mean the counts alone do not precisely characterize comparative risk. They also do not establish whether an event was related to treatment. The registry's safety information should be interpreted as reported, without inferring causation or making a treatment recommendation.

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

The primary result describes the estimated difference in Week 12 ESSDAI change between the GLPG3970 and placebo arms among participants included in the reported analysis. The estimate is -1.4, with a 90% confidence interval from -6.2 to 3.4 and p = 0.617. Its direction favors a larger mean reduction in the GLPG3970 arm, but the interval includes differences in either direction. The result is therefore uncertain and does not establish a clear comparative difference.

It also does not establish that the arms are equivalent. A failure to demonstrate a difference is not the same as demonstrating that any difference is sufficiently small to be unimportant. The record does not report an equivalence or non-inferiority question, a prespecified margin, or a design intended to answer either question.

The registry describes a reduction of at least 3 points in ESSDAI as clinically meaningful. The posted arm means do not indicate how many participants achieved that change, and the registry does not provide a responder analysis in the information reported for the primary outcome. A mean change cannot be assumed to represent the experience of every participant.

The primary analysis includes 8 participants in the GLPG3970 arm and 5 in the placebo arm with available data. This small analysis base and the broad interval limit precision. The full enrollment was 31, but the record does not explain why the primary analysis counts differ from overall enrollment. The study status is terminated, and its reason is not reported in the registry record.

These findings describe the posted trial data and their uncertainty. They do not determine the cause of observed changes, establish a treatment effect, or provide a basis for medical advice. The secondary outcomes and adverse-event counts offer additional descriptive information, but the registry does not report enough detail about multiplicity, missing data, or the full statistical plan to support broader conclusions from them.

15. Why This Trial Matters Statistically

This trial illustrates why the point estimate, confidence interval, p-value, and analysis population should be read together. The estimated Week 12 contrast is -1.4, but the 90% confidence interval from -6.2 to 3.4 spans values in both directions. The p-value of 0.617 alone does not convey that range of uncertainty, and it should not be treated as proof of no difference.

The primary outcome is a continuous disease activity score, and the registry reports a model-based comparison rather than only the arm-level changes. That distinction matters: within-arm change and between-arm contrast answer different questions. A change in both arms does not by itself show a comparative effect, while the modeled contrast is the direct comparison reported for the primary endpoint.

The analysis also highlights the practical importance of knowing who contributed data. Although 31 participants were enrolled, the primary outcome counts are 8 and 5. The registry does not explain this difference or give detailed missing-data information. Such context helps readers judge how broadly a result can be interpreted and how much information supports its estimate.

Finally, the study is listed as terminated and the reason is not reported in the registry record. Statistical interpretation depends not only on a numerical result, but also on design, analysis choices, completeness of reporting, and the scope of the question being answered. The posted record supports a cautious description of the estimated comparison, not a definitive conclusion about treatment effects.

16. 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 primary-outcome analysis includes 8 participants in the GLPG3970 arm and 5 in the placebo arm, although enrollment was 31. The registry does not explain the difference between those counts or report the full disposition of participants. This limits assessment of how representative the analyzed participants are of the enrolled group.

The registry identifies an MMRM analysis but does not report its complete specification. The covariance structure, model terms, and detailed missing-data assumptions are not reported in the registry record. The record says participants with available data were analyzed, but does not explain the amount or reasons for missing Week 12 measurements.

The study is listed as terminated, but the reason is not reported. The planned enrollment target, sample-size justification, and any interim analyses are not reported in the registry record. It is therefore not possible to determine from this record whether the observed enrollment or analysis counts reflect the original statistical plan.

Several outcomes and time points are listed, but a multiplicity strategy is not reported. The full protocol and statistical analysis plan are also not reported, limiting assessment of whether the posted analyses match the original prespecification. The registry gives limited detail for the adverse-event terms and does not establish event causality. These limitations call for interpreting the posted estimates as a record of the reported analysis, with substantial uncertainty and incomplete methodological context.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Study Evaluating the Effects of GLPG3970 Given as an Oral Treatment for 12 Weeks in Adults With Active Primary Sjögren's Syndrome (pSS) — NCT04700280.
• Registry record last updated 2023-09-18; status last verified 2022-11.
• Results first posted 2023-09-18.
• 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.

20. Record Summary

NCT04700280 is a randomized, quadruple-masked, placebo-controlled, parallel-group Phase 2 study of oral GLPG3970 in adults with active primary Sjögren's syndrome. The registry lists enrollment of 31, a 12-week treatment period, and a terminated status. The reason for termination is not reported in the registry record.

The primary endpoint was change from baseline in ESSDAI score at Week 12. The reported mixed-model least-squares mean difference was -1.4, with a 90% confidence interval from -6.2 to 3.4 and p = 0.617. The primary outcome analysis included 8 participants in the GLPG3970 arm and 5 in the placebo arm. The registry also lists secondary outcomes and adverse-event counts. Details of the sample-size justification, multiplicity strategy, and missing-data handling are not reported.