Use of CXCL9 as a Biomarker of Acthar Efficacy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of CXCL9 as a Biomarker of Acthar Efficacy (NCT02523092), a na phase 4 study. The primary outcome is Number of Participants That Show a Decrease in Blood CXCL9 Levels by 50%.

2. Clinical Question

The study’s stated objective was to test whether Acthar gel use in the context of sarcoidosis would be associated with improved symptoms and lung function and with lower levels of predictive blood biomarkers, including CXCL9. This objective combines clinical measures with a laboratory measure. The primary endpoint is specifically a threshold-based count for CXCL9; it is not itself a measure of symptoms, lung function, or the relationship between those measures and CXCL9.

Because the study has no comparator group, the registry’s design cannot directly distinguish a change associated with treatment from changes that might occur over time for other reasons. The record also does not report an estimated treatment effect or outcome results, so the clinical question cannot be answered from the posted results.

3. Trial Design

The registry identifies NCT02523092 as a Phase 4 study sponsored by the University of California, San Francisco, with the title “Use of CXCL9 as a Biomarker of Acthar Efficacy.” Sarcoidosis is the listed condition, and Acthar gel is the listed drug intervention. The study is described as single-group, with allocation listed as not applicable and masking listed as none. The registry reports enrollment of 2 and a status of terminated.

The recorded start date is 2022-11-03, and the recorded primary completion date is 2025-01-31. These dates and the termination status describe the registry record; they do not establish when each participant began or stopped treatment, or why the study was terminated. The reason for termination is not reported in the registry record.

The intervention description outlines a baseline-monitoring period of 4 weeks, followed by Acthar gel by intramuscular or subcutaneous injection. The initial described dose is 40 U every 72 hours or twice per week for 4 weeks. The description then says the dose would increase to 80 U at a similar frequency for 8 weeks and up to 16 weeks. This is a registry description of the intended regimen, not confirmation of actual exposure or adherence. Participant-level dosing and treatment duration are not reported in the registry record.

A single-group design can describe within-participant changes over time, but it does not provide a concurrent control for comparison. The record does not report a randomization procedure, and no randomized comparison is described. Details on eligibility, recruitment, study locations, and protocol deviations are not reported in the registry record. The registry lists three outcome measures, including the primary CXCL9 count and secondary measures concerning forced vital capacity and dyspnea. It reports zero analyses.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: for the two participants, blood samples were analyzed before starting Acthar gel and at the last visit time point at 6 months. Therefore, two time points were analyzed per participant.

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 Number of Participants That Show a Decrease in Blood CXCL9 Levels by 50%, measured over within 6 months.

The primary endpoint is the number of participants whose blood CXCL9 level decreased by 50% or more within 6 months. The registry describes measuring gene expression for CXCL9 using a quantitative polymerase chain reaction assay on whole blood samples. It says the change in cycle threshold from before starting medication to the end of treatment was calculated, then used to determine whether each participant met the stated decrease threshold. The outcome is a participant count, rather than a continuous estimate of the size of the change.

A threshold-based endpoint can provide a direct count of participants meeting a prespecified definition of change. It may be easier to interpret than a laboratory measurement alone, but it discards information about how far a participant’s result lies above or below the threshold. A count also depends on the definition and measurement process, so interpretation requires clear reporting of the observed count and the number evaluated.

The endpoint is used because the study’s stated objective concerns CXCL9 as a predictive blood biomarker in the context of Acthar gel use. However, meeting the decrease threshold does not by itself establish that CXCL9 predicts clinical improvement, or that a change in the biomarker corresponds to a change in symptoms or lung function. The registry lists two participants with blood samples analyzed at baseline and the last visit time point at 6 months, but the number meeting the threshold is not reported in the registry record. Assay details beyond the description, including how missing samples or indeterminate measurements were handled, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary at the participant level: each participant either meets the stated decrease threshold or does not. The registry then defines the reported outcome as a count of participants who meet it. For this kind of endpoint, a complete report would ordinarily make clear both the count meeting the criterion and the number of participants evaluated. The record describes samples for two participants, but it does not report the count meeting the criterion or an analysis of the endpoint.

What does a participant count communicate?

General statistical explanation: a count records how many observed participants fall into a category. A count is easy to understand, but its interpretation depends on the group being counted and the denominator used. A count on its own does not tell the reader how uncertain the result is or how well it might represent a broader population. For a small group, a change in one participant’s classification can materially alter the pattern. The registry does not provide a confidence interval for the CXCL9 endpoint.

A confidence interval is a statistical range intended to express uncertainty around an estimate under a specified method. It is not a guarantee that the true value lies within that range, and its usefulness depends on appropriate methods and sufficiently informative data. No interval or method for estimating uncertainty is reported in the registry record. With only the posted outcome description and no reported count, a numerical estimate and its uncertainty cannot be assessed.

Why is the design important?

General statistical explanation: a single-group before-and-after design can describe changes observed in the same participants over time. It does not, by itself, show what would have happened to those participants over the same period without the intervention. A concurrent comparator can help address that question, while random allocation, when used, helps balance other influences between groups. This registry record describes neither a control group nor random allocation. The primary endpoint can therefore be read only as a planned within-group biomarker outcome, not as a controlled estimate of treatment effect.

Masking is listed as none. General statistical explanation: masking can reduce the influence of knowledge about treatment assignment on some aspects of care, measurement, or assessment, depending on what is masked and how outcomes are obtained. The record does not describe masked assessment or further procedures to limit measurement bias. The laboratory assay is identified, but detailed assay conduct and quality-control information are not reported in the registry record.

What is the role of the planning illustrations?

The planning calculations are described as illustrations based on an observed effect, not as the study’s own design justification. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Those assumptions do not match the registry’s single-group design, which has no two-arm allocation. The registry does not report a prospective sample-size justification or explain how the study enrollment was selected. The planning illustrations should not be read as observed power, as evidence that the trial had a particular probability of detecting an effect, or as a substitute for results. No numerical planning estimates are repeated.

General statistical explanation: power is a planning concept tied to assumptions about the effect, variability, analysis, and design. Calculating power after a study from the observed effect does not resolve uncertainty in the estimate and is not a useful substitute for reporting the result with an appropriate uncertainty interval. The registry does not report a power analysis for this study.

What analysis details are available?

The registry reports zero analyses. It does not describe a statistical test, model, adjustment strategy, or method for estimating uncertainty for the primary endpoint. The endpoint description gives the assay and threshold, but the statistical analysis plan is not reported in the registry record. Details about how cycle-threshold measurements were transformed into the stated decrease, how borderline results were treated, and whether the endpoint was assessed at a prespecified visit are not reported in the registry record.

The two secondary outcomes are expressed as participant improvement criteria, but the record does not report their analysis methods or results. General statistical explanation: when several outcomes are examined, multiplicity can increase the chance of observing an apparently notable result by chance if each is tested separately. A prespecified hierarchy or adjustment can help define how multiple findings are interpreted. The registry does not report whether multiplicity was addressed.

Overall, the available statistical description is enough to identify the type of primary outcome and its threshold, but not to reproduce or evaluate an analysis. The record does not provide participant-level values, outcome counts, uncertainty estimates, or a detailed analysis plan.

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("Observational Arm")
n      <- c(2)
events <- c(0)
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  Observational Arm  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: the primary count of participants with a 50% or greater decrease in CXCL9, plus secondary measures concerning improvement in FVC liters and dyspnea score. The primary outcome description specifies a timeframe of within 6 months. The listed secondary outcome names do not, by themselves, establish their analysis timepoints, assessment rules, or statistical methods. Further details are not reported in the registry record.

Multiplicity concerns arise when a study examines multiple outcomes or makes multiple statistical comparisons. General statistical explanation: the more separate opportunities there are to identify a result as noteworthy, the more important it is to define in advance which outcomes are primary and how other findings will be handled. A hierarchy or statistical adjustment may be used, but the registry does not report a multiplicity strategy, a testing hierarchy beyond the outcome labels, or whether any adjustment was planned.

The registry reports zero analyses, and results for the primary and secondary outcomes are not reported in the registry record. It also does not report methods for handling missing measurements, incomplete follow-up, or participants who did not complete treatment. The primary outcome description says that two participants had samples analyzed before treatment and at the last visit time point at 6 months. This does not explain whether other scheduled samples were collected or how missing or unusable results would have been addressed.

Analysis populations are not reported in the registry record. There is no description of whether analyses were intended to include all enrolled participants, only those who received treatment, or only those with available endpoint measurements. The record’s sample description should not be treated as a complete participant-flow account. Without these details, it is not possible to assess the extent or potential influence of missing data, or to determine precisely which participants would contribute to each outcome analysis.

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 0% reporting threshold.

The registry reports zero serious adverse events among the 2 participants listed as at risk in the Acthar Gel group. It also reports zero other adverse events among the 2 participants listed as at risk, and zero deaths. No serious adverse event terms are listed.

These are recorded counts, not estimates of risk that can establish the absence of harm. With a small number of participants, the absence of a recorded event does not rule out events that were not observed in this study or events too uncommon to appear in a study of this size. It also does not establish that all possible events were captured. General statistical explanation: event counts are most informative when the observation period, event definitions, ascertainment procedures, and completeness of reporting are clear.

The registry does not report further details about safety monitoring, the adverse-event collection period, event definitions, severity grading, or whether any participants discontinued treatment because of an adverse event. The reported figures should therefore be read as the safety counts recorded in the registry, not as a comprehensive assessment of safety or a comparison with another treatment group.

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

The record establishes that the study was designed to examine Acthar gel use in sarcoidosis and included a primary biomarker endpoint: a count of participants with a 50% or greater decrease in blood CXCL9 within 6 months. It also identifies secondary outcomes concerning FVC and dyspnea. The outcome description refers to blood samples from two participants at baseline and at the last visit time point at 6 months.

What the record does not establish is whether either participant met the CXCL9 threshold, whether FVC or dyspnea improved, or whether biomarker changes were associated with changes in symptoms or lung function. Those results are not reported in the registry record, and the record reports zero analyses. Consequently, it cannot support a conclusion that Acthar gel improved or did not improve any outcome, or that CXCL9 did or did not function as a predictive biomarker.

The single-group design also limits causal interpretation. A change from baseline, even if reported, would not by itself show that treatment caused the change, because there is no concurrent comparison group described in the record. The planned focus on changes and correlations should not be mistaken for evidence that such changes or relationships were observed.

The reported enrollment of 2 sharply limits how much can be learned about the consistency of outcomes across participants. General statistical explanation: small studies generally provide little information about between-participant variation and often yield imprecise estimates, especially for outcomes expressed as counts. No effect estimate or confidence interval is available in the registry record to characterize uncertainty for the primary outcome.

The terminated status is a fact about the registry record, but the reason for termination is not reported. It should not be interpreted as evidence of benefit, lack of benefit, or a safety problem. The appropriate reading is that the record documents a study objective, design, regimen description, and limited outcome and safety information, while leaving the central efficacy and biomarker questions unanswered.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between measuring a biomarker and validating it as a predictor of clinical outcome. The stated objective links CXCL9 with Acthar gel use, symptoms, and lung function, while the primary endpoint counts participants crossing a specified biomarker-change threshold. A biomarker endpoint can describe a laboratory response, but validation as predictive requires evidence about how the biomarker relates to clinical outcomes. Such an association result is not reported in the registry record.

The design also illustrates why outcome definitions and study structure matter. The threshold of a 50% or greater decrease gives a clear classification rule, but the published count and the number evaluated are needed to understand the result. The registry describes samples for two participants yet does not report how many met the threshold. Without the result, neither the magnitude nor the uncertainty of the endpoint can be assessed.

The single-group structure is important for interpretation. Within-participant measurements can be valuable for describing change, but without a concurrent comparator they cannot separate treatment-associated change from other influences over time. This limitation applies even when a laboratory measure is objective. It is especially relevant when a study’s goal extends beyond describing biomarker change to drawing conclusions about efficacy or links to clinical outcomes.

The record further demonstrates the value of complete reporting. Outcome counts, uncertainty estimates, analysis methods, participant flow, missing-data handling, and reasons for termination each contribute to evaluating a study. The registry reports zero analyses and does not provide the primary or secondary outcome results. As a result, the study is informative about the question researchers intended to address and about the planned endpoint definition, but it does not furnish the results needed to answer that question.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation is the lack of reported outcome results. The registry does not state the number of participants meeting the primary CXCL9 threshold, and it does not report the secondary outcome results. It lists zero analyses. Without observed outcome counts or estimates, the findings and their precision cannot be evaluated.

Enrollment was 2, and the primary outcome description refers to measurements from two participants. This offers very limited information for judging variation between participants or the stability of a count-based result. The registry does not provide individual measurements, uncertainty intervals, or a detailed account of participant follow-up. Although the record lists a last visit time point at 6 months for the described samples, it does not report whether all planned visits occurred or whether anyone discontinued.

The single-group design has no concurrent control described, so it cannot support a controlled comparison. Masking is listed as none, and further safeguards against bias in outcome assessment are not reported in the registry record. The study’s stated interest in relationships between biomarkers and clinical outcomes cannot be evaluated because no association analysis or results are reported.

Further limitations include the absence of a reported sample-size justification, statistical analysis plan, multiplicity strategy, and missing-data methods. The reason for termination is not reported. The intervention description does not establish actual treatment received, adherence, or participant-level duration. These gaps restrict interpretation of both efficacy and safety. The safety record reports zero serious events, zero other events, and zero deaths among the listed participants at risk, but it does not supply enough detail to treat those counts as a comprehensive safety assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Use of CXCL9 as a Biomarker of Acthar Efficacy — NCT02523092.
• Registry record last updated 2026-04-30; status last verified 2026-04.
• Results first posted 2026-04-30.
• 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

NCT02523092 is a terminated Phase 4, single-group study sponsored by the University of California, San Francisco, concerning Acthar gel use in sarcoidosis. The registry reports enrollment of 2, with no masking and allocation listed as not applicable. The recorded start date is 2022-11-03, and the primary completion date is 2025-01-31.

The primary outcome is the count of participants with a 50% or greater decrease in blood CXCL9 within 6 months. The outcome description refers to samples from two participants before treatment and at the last visit time point at 6 months. Secondary outcomes concern FVC and dyspnea. Outcome results are not reported in the registry record, which lists zero analyses. Safety counts are zero serious adverse events, zero other adverse events, and zero deaths among the 2 participants listed as at risk. The reason for termination and detailed analysis methods are not reported in the registry record.