Effect of OC000459 on Moderate to Severe Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of OC000459 on Moderate to Severe Atopic Dermatitis (NCT02002208), a randomized phase 2 study. The primary outcome is Change From Baseline in Eczema Area and Severity Index (EASI) Compared to Placebo at Week 16.

2. Clinical Question

The trial’s stated purpose also refers to disease severity and preventing flares. The primary endpoint focused on change in EASI, a score describing eczema signs and the extent of affected skin. A secondary outcome was the rate of flares over 16 weeks. The primary comparison therefore addresses a measured change in disease severity at a specified follow-up, while the secondary outcome concerns flare frequency across the stated period.

The record describes random allocation, double masking, and a parallel-group comparison. These design features support a comparison between the treatment and placebo groups, but they do not by themselves establish how missing observations, adherence, or analysis populations were handled. Those details are not reported in the registry record. The statistical result should be read as a comparison of the posted group summaries, not as a complete account of every planned or performed analysis.

3. Trial Design

This was a phase 2 randomized, double-blind, placebo-controlled, parallel-group study sponsored by Atopix Therapeutics, Ltd. The condition listed was atopic dermatitis. The registry record gives an enrollment of 142 and a status of completed. The study start is recorded as 2013-10, and primary completion as 2015-09.

Participants were assigned to OC000459 tablets or placebo tablets. The OC000459 regimen was 50 mg orally once a day; placebo was taken orally once a day. The double-blind designation indicates that the record describes masking of participants and investigators, but further details about who was masked or how masking was maintained are not reported in the registry record. The randomization method, allocation concealment procedures, and any stratification factors are also not reported in the registry record.

The primary endpoint was change from baseline in EASI compared with placebo at Week 16. The record says EASI was measured at baseline, identified as week 0, and 16 weeks after dosing. The outcome population is described as adjusted mean change from baseline at Week 16. A secondary outcome was rate of flares over 16 weeks. No further detail about how a flare was defined is reported in the registry record.

Posted outcome summaries list 69.0 participants for the OC000459 EASI result and 70.0 for placebo. Safety figures use at-risk counts of 70 and 71, respectively. These outcome-specific figures should not be treated as interchangeable; the registry record does not explain the differences in the reported counts. It also does not report the trial’s original sample-size justification, full protocol, analysis populations, or handling of missing outcome data.

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: Adjusted mean change from baseline EASI at Week 16

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 Change From Baseline in Eczema Area and Severity Index (EASI) Compared to Placebo at Week 16, measured over EASI was measured at baseline (week 0) and 16 weeks after dosing..

EASI is a clinical scoring system for the signs and extent of eczema. It grades severity and affected area in four body regions: head and neck, trunk, upper extremities, and lower extremities. The score ranges from 0 to 72, with higher scores corresponding to more severe disease. The registry description lists strata from clear through very severe and states that a reduction of 7 or more is considered clinically meaningful when assessing response to therapy.

The primary endpoint is the mean change from baseline in EASI at Week 16, compared with placebo. A change score expresses how the measure differs from a participant’s baseline; a negative change indicates a lower EASI score at follow-up than at baseline. Comparing group mean changes helps describe the average difference between assigned groups over the assessment period. It does not show how every participant changed, and a mean can conceal variation in individual responses.

The endpoint is relevant to the stated question because EASI combines assessments of eczema signs and the extent of affected skin. The stated clinically meaningful reduction applies to a reduction in EASI when assessing response; it should not be confused with the between-group mean difference. The registry record does not report a responder analysis applying that threshold. Nor does the record provide confidence intervals for the individual adjusted group means, although it provides an interval for the posted comparison.

7. Results Posted in the Registry

• OC000459 Tablets: mean -3.80 versus -6.10 on control; difference 2.30 (95% CI -2.45 to 7.05), standardized effect d = 0.16; z-test p = 0.343.

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.

Rate of Flares

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • OC000459 Tablets: mean 2.88 versus 2.65 on control; difference 0.23 (95% CI -1.08 to 1.54), standardized effect d = 0.06; z-test p = 0.728.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OC000459 Tablets and the control. The interval gives the range of effects that remain compatible with the data.

The record lists one secondary outcome: rate of flares over 16 weeks. Its group summaries and an unadjusted comparison are posted. Taken together with the primary endpoint, the outcomes address related but distinct aspects of atopic dermatitis: EASI describes signs and affected extent at the Week 16 assessment, whereas the flare outcome summarizes episodes during the stated period.

The secondary result does not change the interpretation of the primary comparison. It provides additional context but is not a replication of the EASI endpoint: the outcome scale and the question differ. The registry record does not report a definition of a flare, a planned role for the secondary endpoint in drawing conclusions, or a multiplicity adjustment. The secondary finding should therefore be treated with more caution than a prespecified primary result, especially if several outcomes or analyses were considered.

In general, examining multiple outcomes can increase the chance that at least one result appears unusual by chance. Adjustments or a prespecified testing hierarchy can help control that issue, but neither is reported in the registry record. The reported secondary comparison is unadjusted. It should not be interpreted as independent confirmation of the primary result, nor should it be used to resolve uncertainty in the primary estimate.

The overall statistical pattern is that the record contains a primary EASI comparison and a single posted secondary flare outcome, with no reported analyses beyond those outcome summaries. The registry record does not provide enough detail to assess whether other secondary outcomes were collected but not posted, how the endpoints were prioritized in the analysis, or whether multiplicity was addressed in the full study plan.

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

• Rate of Flares

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical EASI score, summarized as a mean change from baseline. The registry record reports adjusted mean changes and standard errors for the two groups, then gives a mean difference with a confidence interval and an unadjusted p-value. The adjustment method, model specification, and details of the sponsor’s inferential analysis are not reported in the registry record. The posted comparison is therefore most safely described as a recalculated unadjusted comparison from summary statistics.

What does a mean change describe?

In general, a mean change summarizes the average difference between follow-up and baseline measurements in a group. It can be useful when the outcome has a meaningful numerical scale and each participant has measurements at both times. A group mean does not describe the full distribution: some participants may have larger changes, smaller changes, or changes in the opposite direction. The registry record does not provide individual-level outcomes or a distribution of participant-level changes.

Here, the reported mean changes are -3.8 for OC000459 and -6.1 for placebo. The comparison estimate is 2.3 for OC000459 minus placebo. This direction follows from the posted values: a positive contrast means the OC000459 mean change is higher, or less negative, than the placebo mean change. That arithmetic description does not itself establish clinical importance. The EASI description gives a clinically meaningful reduction threshold for assessing response, but the registry record does not report a responder analysis based on that threshold.

What does the standard error tell the reader?

In general, a standard error describes the uncertainty in an estimated group mean, rather than the spread of individual participants’ measurements. It tends to be smaller when a mean is estimated more precisely. It should not be read as if it were the standard deviation, which describes variability among observations. The EASI arm summaries list standard errors of 1.72 and 1.71. The flare outcome, by contrast, lists standard deviations. These two types of spread measure are not interchangeable.

In general, an adjusted mean can account for variables or features specified in an analysis model. Whether and how that happened in this trial is not reported in the registry record. The label “adjusted mean change” does not identify the covariates, model, missing-data assumptions, or estimand. The posted standard errors should therefore be understood as the registry’s reported uncertainty measures, without inferring an unreported model.

How should the mean difference be read?

The mean difference is a contrast between group means. The stated comparison is OC000459 minus placebo, so zero represents equal group means on that contrast scale. A positive value indicates a higher mean change in the OC000459 group; a negative value indicates a lower mean change in that group. Since change is measured on the EASI scale, the estimate is expressed in EASI units. The recalculated estimate of 2.3 is not an adjusted difference unless the underlying analysis explicitly says so; the record does not describe such an adjustment for the contrast.

In general, an unadjusted comparison uses the posted group summaries without accounting for additional participant-level covariates. Recalculation from summary statistics can help readers understand the scale and direction of the contrast, but it cannot reproduce analyses that depend on individual data, covariate adjustment, or complex missing-data methods. The registry record does not report a full analysis output to compare against this simple calculation.

What does the p-value contribute?

In general, a p-value is calculated under a null hypothesis, often that the group contrast is zero, and a statistical model or test. It describes the compatibility of the observed data with that model; it is not a measure of effect size or clinical importance. The unadjusted p-value for the primary comparison is 0.343. The record does not report the test procedure or a prespecified significance threshold, so the p-value should not be treated as a complete account of the trial’s planned decision rule.

The p-value and confidence interval are related ways of expressing uncertainty, but neither resolves limitations in the underlying data or analysis. A value that is not small does not prove equality. Conversely, a small p-value would not by itself establish that a difference is meaningful to patients. For this trial, the point estimate, interval, outcome definition, and analysis reporting all matter to interpretation.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. This matters especially for count outcomes, such as flare counts, because a model that understates variability may produce uncertainty estimates that are too narrow. The secondary flare summaries have standard deviations that differ between groups, and the record does not describe a count model or an over-dispersion assessment. No particular model should be inferred from the mean and standard deviation summaries alone.

The registry record reports a continuous mean-based summary for flares, not a detailed distribution or event-time analysis. A mean can summarize counts, but it does not show whether counts are concentrated among a few participants or broadly distributed. The absence of participant-level distributions and model details limits what can be concluded about the flare comparison.

These explanations of means, standard errors, confidence intervals, p-values, and over-dispersion are general statistical context. They do not add an unreported trial method. The record does not report randomization details, analysis populations, missing-data procedures, interim analyses, or the original statistical plan. Those omissions constrain any attempt to reproduce or fully audit the analyses.

11. Confidence Intervals and Precision

The recalculated primary mean difference was 2.3 EASI units, with a 95% confidence interval from -2.454 to 7.054. In general, a confidence interval describes a range of values reasonably compatible with the observed data under the calculation’s assumptions. A 95% confidence procedure would cover the true parameter in 95% of repeated samples if its assumptions held; it does not mean there is a 95% probability that this particular interval contains the true value.

The interval includes zero and spans values on both sides of it. This indicates that the estimated direction is uncertain: the posted summary statistics do not rule out a lower mean change in the OC000459 group or a higher one. The interval also includes contrasts of appreciable size on the EASI scale. Its breadth limits precision; the point estimate alone would give an incomplete impression of what the data support.

The individual group means are reported with standard errors of 1.72 and 1.71, but no confidence intervals for those means are posted. The comparison interval is based on a recalculation from summary statistics, and the record does not describe the trial’s full analysis model. Therefore, the interval should be read as an unadjusted summary-based estimate, not as confirmation that it reproduces a model-based sponsor interval.

In general, precision is affected by the amount of information and the variability of the outcome. The registry’s outcome-specific participant counts and standard errors offer some context, but the record does not explain all differences between outcome counts or provide individual-level data. Precision is consequently best judged from the posted contrast and interval together, with the limitations of the record in view.

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 figures are participants per arm, not total events. They are illustrations based on the observed effect, not the original trial’s design assumptions. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The original sample-size justification and assumptions are not reported in the registry record.

For the primary EASI comparison, planning for 100% of the observed effect gives 607 participants per arm for 80% power and 813 for 90% power. Planning for 75% gives 1,079 and 1,444 participants per arm, respectively; planning for 50% gives 2,427 and 3,249. For the flare comparison, the corresponding figures are 4,525 and 6,058 for 100%, 8,045 and 10,769 for 75%, and 18,100 and 24,231 for 50%.

In general, 80% power means that, if the assumed effect and model were true, the design would have an 80% chance of detecting an effect using the stated test criterion. The 90% column uses a higher target chance under those assumptions. Smaller effects require more participants to achieve a given target power, which is why the planning figures rise as the assumed fraction falls. These are planning illustrations, 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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 2.300; pooled standard deviation σ = 14.297.
2. n = 2 × (1.96 + 0.842)² × 14.297² / 2.300² = 606.6, rounded up to 607 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
delta <- 2.3                      # observed difference in means
sigma <- 14.2972142148941                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2002208)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 607 (80% power), 813 (90% power)
 75% of observed effect: n per arm = 1,079 (80% power), 1,444 (90% power)
 50% of observed effect: n per arm = 2,427 (80% power), 3,249 (90% power)
power.t.test: 607.5 
Simulated power at n = 607 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary EASI endpoint and a secondary rate-of-flares outcome. It lists two outcome measures and reports zero analyses; the secondary outcome has no reported analyses beyond the posted summary comparison. The record does not describe a statistical testing hierarchy, an adjustment for multiple comparisons, or a family of hypotheses. Whether the study used a multiplicity strategy is not reported in the registry record.

In general, multiplicity arises when multiple outcomes, time points, groups, or analytic choices are tested. Without an appropriate plan, the chance of at least one apparently notable result can increase. This is why a single secondary p-value should not carry the same weight as a primary result specified in advance, especially when the statistical plan and testing hierarchy are unavailable. No claim about the trial’s actual approach to multiplicity can be made from the posted record.

Missing-data methods are also not reported in the registry record. It does not state how many participants had missing Week 16 EASI measurements, how missing values were handled, whether all randomized participants were included, or whether any sensitivity analyses were conducted. The outcome-specific counts differ across the efficacy and safety summaries, but the record does not explain why. These counts alone do not establish whether data were missing or how participants were analyzed.

The analysis populations are not reported in the registry record. It is therefore unclear from the posted information whether the EASI result corresponds to an intention-to-treat population, a per-protocol population, or another defined set. The record also does not report the model used to obtain adjusted mean changes, covariates included, assumptions about repeated measurements, or procedures for handling protocol deviations.

No interim analyses or stopping rules are reported in the registry record. Their absence from the posted information should not be taken as proof that none occurred. Taken together, the missing details limit reproducibility and prevent a full assessment of how the statistical analysis was planned and implemented.

15. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2.5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: worsening atopic dermatitis (4.2%), solitary plasmacytoma (1.4%), staphylococcal infection (1.4%), anaphylaxis (1.4%), ecg abnormality (1.4%).

The safety summaries report serious adverse events among participants at risk: 2 in the OC000459 group, with 70 at risk, and 6 in the placebo group, with 71 at risk. These are group-specific counts as recorded. They should be interpreted as descriptive safety information rather than as a formal comparative analysis; the registry record does not provide a confidence interval or inferential test for this comparison.

The record lists worsening atopic dermatitis at 4.2% among the top serious adverse event terms, along with Solitary Plasmacytoma, Staphylococcal infection, Anaphylaxis, ECG abnormality, and Gastroenteritis, each at 1.4%. The registry record does not identify a group for these listed term percentages, so they should not be attributed to either arm from the information posted. Death counts are not reported in the registry record.

These summaries do not describe all aspects of safety, such as timing, duration, severity grading, or causal attribution for each event. The figures are limited to the adverse-event information posted and should not be treated as a complete safety profile.

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

The posted primary outcome describes mean EASI change from baseline at Week 16 in the two randomized groups. The group mean changes were -3.8 for OC000459 and -6.1 for placebo. The recalculated unadjusted difference was 2.3 EASI units, with a confidence interval that included zero. These results show uncertainty about the direction and size of the between-group contrast in the posted summary data.

That uncertainty is not evidence that the groups were equivalent. Demonstrating equivalence or non-inferiority requires an appropriate prespecified design, margin, and analysis; those are not reported in the registry record. Nor does a confidence interval crossing zero prove that there is no effect. It indicates that the posted comparison does not tightly distinguish a difference from no difference under the calculation’s assumptions.

The record’s EASI description states that a reduction of 7 or more is considered clinically meaningful when assessing response to therapy. That statement concerns an EASI reduction and should not be applied as if it were a threshold for the between-group mean difference. The registry record does not report how many participants met this threshold, nor does it report a responder analysis. Group means cannot show how many individuals had a clinically meaningful change.

The trial record also does not establish results beyond the specified Week 16 primary assessment or the flare outcome over 16 weeks. It does not provide a full account of missing data, analysis populations, or methods. The posted results therefore support a bounded description of the recorded outcomes, not a broad conclusion about all people with atopic dermatitis or about treatment effects beyond the study conditions.

Statistical interpretation should remain separate from medical advice. The data summaries characterize the comparison and its uncertainty; they do not direct an individual treatment choice. They also do not settle questions that the registry record does not address, such as longer-term outcomes or the consistency of effects across participant subgroups.

17. Why This Trial Matters Statistically

This trial illustrates why the point estimate, its uncertainty, and the outcome definition need to be read together. The primary endpoint is a mean change in a severity score, while the reported estimate is a contrast between groups. The estimate’s direction can be described from the group summaries, but the confidence interval spans values on both sides of no difference. A single point estimate without its interval would overstate how clearly the data identify the direction and magnitude of the contrast.

The record also highlights the difference between a reported adjusted group mean and an unadjusted comparison recalculated from summary statistics. The term “adjusted” signals that an analysis may have accounted for other factors, but the relevant method is not reported in the registry record. Without that information, readers cannot reproduce the adjusted analysis or determine whether the recalculated contrast matches it.

The clinically meaningful reduction statement is another important distinction. A threshold for an individual’s EASI reduction is not automatically a threshold for the difference between group means. A trial can report a group mean contrast without reporting the proportion of participants who achieved a threshold response. Those analyses answer different questions.

Finally, the secondary flare outcome and safety summaries add context but do not remove uncertainty in the primary result. The absence of reported multiplicity handling, analysis populations, and missing-data methods limits the strength of further interpretation. The statistical value of this record lies in making those boundaries visible: it reports useful outcome summaries, while leaving important analysis details unavailable.

18. 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.

Several limitations are specific to the information posted for this trial. The primary outcome is described as an adjusted mean change, but the adjustment method and model are not reported in the registry record. The recalculated contrast is based on the summary statistics and is unadjusted. This means it may not reproduce the analysis used to generate the adjusted outcome summaries.

The posted primary comparison has a confidence interval that includes zero and extends across a broad range of EASI differences. This limits precision and leaves uncertainty about the direction and size of the contrast. The record does not provide confidence intervals for the separate group means, participant-level data, or distributions of individual changes.

The record does not report the EASI analysis population, handling of missing Week 16 data, model assumptions, covariates, or sensitivity analyses. It also does not explain differences between efficacy outcome counts and safety at-risk counts. Without these details, readers cannot fully assess attrition or determine whether the groups summarized for each outcome correspond to the same analysis population.

The secondary flare outcome is not defined in detail, and its statistical analysis is not described. Multiplicity procedures and the role of secondary outcomes in the planned testing strategy are not reported in the registry record. The listed serious adverse event term percentages are not assigned to groups in the posted information, and details such as event timing and attribution are unavailable. These limitations restrict both the clinical interpretation and reproducibility of the posted results.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effect of OC000459 on Moderate to Severe Atopic Dermatitis — NCT02002208.
• Registry record last updated 2018-03-26; status last verified 2018-02.
• Results first posted 2016-12-08.
• 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.

22. Record Summary

NCT02002208 is a completed randomized, double-blind, placebo-controlled, parallel-group phase 2 study sponsored by Atopix Therapeutics, Ltd. The condition was atopic dermatitis, and the trial compared OC000459 tablets, 50 mg orally once a day, with placebo tablets taken orally once a day. The registry record gives an enrollment of 142, a study start of 2013-10, and primary completion in 2015-09.

The primary endpoint was adjusted mean change from baseline in EASI at Week 16. The posted arm means were -3.8 for OC000459 and -6.1 for placebo; the recalculated unadjusted mean difference was 2.3, with a confidence interval from -2.454 to 7.054 and an unadjusted p-value of 0.343. The record also lists rate of flares over 16 weeks as a secondary outcome.

Key analysis details, including the model, missing-data procedures, analysis populations, and multiplicity approach, are not reported in the registry record. The posted results describe the available summaries but do not provide a complete account of the trial’s statistical analysis.