Trial of IMO-3100 in Patients With Moderate to Severe Plaque Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of IMO-3100 in Patients With Moderate to Severe Plaque Psoriasis (NCT01622348), a randomized phase 2 study. The primary outcome is Mean Epidermal Thickness at End-of-Treatment (EOT) Compared to Pre-treatment.

2. Clinical Question

The clinical question is about a measured tissue characteristic, not a direct report of symptoms, daily functioning, or long-term disease course. The posted results contain one primary outcome measure: change from pretreatment baseline to end-of-treatment in epidermal thickness of the index lesion. The trial enrolled 44 participants overall. Arm-level results list 15 participants for IMO-3100 at 0.16 mg/kg, 14 for IMO-3100 at 0.32 mg/kg, and 15 for placebo.

The trial's stated purpose was to evaluate different dose levels against placebo over a four-week treatment period. The record identifies a primary endpoint timeframe of 8 weeks, while the official title describes a 4-week trial. Further details about the timing of tissue measurements or follow-up are not reported in the registry record. The results therefore address the recorded endpoint and its stated timeframe, rather than every possible clinical effect of treatment.

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel phase 2 trial of IMO-3100 in patients with moderate to severe plaque psoriasis. The registry lists quadruple masking. It records an enrollment of 44 and a completed status. The study start is listed as 2012-05 and primary completion as 2012-11. These dates describe the registry record and do not provide further information about the duration of each participant's follow-up.

Participants were assigned to IMO-3100 at 0.16 mg/kg, IMO-3100 at 0.32 mg/kg, or saline for injection as placebo. The lower dose was administered subcutaneously once weekly, calculated from body weight at screening, with a maximum of 20 mg per injection. The higher dose was administered subcutaneously weekly for four weeks, also based on screening body weight, with a maximum of 40 mg per injection. The registry describes the treatment purpose as evaluation of different dose levels against placebo for four weeks.

The parallel design means participants were assigned to a treatment group rather than described as switching among the trial groups. Randomization and masking are recorded, but the randomization procedure, allocation ratio, concealment process, and specific masking roles are not reported in the registry record. The record also does not report whether treatment adherence or protocol deviations affected the analyses.

The primary outcome was a continuous measure: mean change in epidermal thickness of the index lesion from pretreatment baseline to end of treatment, measured in millimeters. Its stated population is the ITT population, and its timeframe is 8 weeks. The number of outcome measures posted is one, and no secondary outcomes are posted. Although arm summaries and two pairwise comparisons are reported, no sponsor analysis is listed. Details of the trial's original statistical analysis plan, sample-size justification, and handling of missing outcome data 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: 48 patients met inclusion/exclusion criteria; 4 were not randomized. The reasons for not randomizing these patients were: 2 patients withdrew consent, 1 whose calcium levels did not meet the criteria for randomization, and 1 for whom the study was closed prior to randomization

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population

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: ITT population

6. Primary Endpoint

The registry lists the primary outcome as Mean Epidermal Thickness at End-of-Treatment (EOT) Compared to Pre-treatment, measured over 8 weeks.

The primary endpoint is the change from pretreatment baseline to end-of-treatment in epidermal thickness of the index lesion. Epidermal thickness is a continuous measurement, and the registry expresses it in millimeters. The arm results report a mean change and standard deviation for each group. A negative mean represents a decrease in the measured thickness from baseline, while a positive mean represents an increase. This description concerns the direction of the recorded measurement; it does not by itself establish the clinical importance of a change.

For IMO-3100 at 0.16 mg/kg, the reported mean change was -8.8 with a standard deviation of 85.9. For IMO-3100 at 0.32 mg/kg, the mean change was -48.5 with a standard deviation of 91.0. For placebo, the mean change was 17.3 with a standard deviation of 102.8. The registry identifies the endpoint population as ITT and gives the timeframe as 8 weeks. More detail about how the endpoint measurement was collected, whether readings were blinded, or how repeated measurements were combined is not reported in the registry record.

A continuous tissue measure can capture a graded change rather than reducing results to categories such as improved or not improved. That makes it possible to describe the average change and the variation among participants. However, the registry record does not state how a particular amount of change should be interpreted clinically, whether the measure was validated for this use, or what difference would be considered meaningful to patients. The endpoint therefore provides a specific quantitative comparison, but the posted information alone does not establish its clinical significance.

7. Results Posted in the Registry

• IMO-3100 at 0.16 mg/kg: mean -8.80 versus 17.30 on control; difference -26.10 (95% CI -93.89 to 41.69), standardized effect d = -0.28; z-test p = 0.451.
• IMO-3100 at 0.32 mg/kg: mean -48.50 versus 17.30 on control; difference -65.80 (95% CI -136.36 to 4.76), standardized effect d = -0.68; z-test p = 0.068.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: a mean change in epidermal thickness measured in millimeters. A continuous outcome can take a range of values, rather than only a limited set of categories. For each treatment group, the mean describes the average recorded change, while the standard deviation describes how spread out participant measurements are around that mean. General statistical interpretation: the mean is sensitive to unusually high or low values, and the standard deviation does not reveal whether the distribution is symmetric or whether a few observations are especially influential. The registry record does not provide individual values or enough distributional detail to assess those features.

What does the mean difference compare?

The reported mean differences compare each IMO-3100 group with placebo. The placebo mean change is 17.3. The reported contrasts are -26.1 for IMO-3100 at 0.16 mg/kg and -65.8 for IMO-3100 at 0.32 mg/kg. A negative contrast means that the active-group average change is lower than the placebo-group average change. This is a comparison of changes, not a comparison of endpoint thickness values alone. The registry record does not report a direct statistical comparison between the two active doses.

The confidence intervals and unadjusted p-values accompanying those contrasts are recalculated from the posted summary statistics. They are not identified as sponsor analyses, and the record lists no sponsor analyses. The recalculated interval for the lower dose is -93.89 to 41.69, with p = 0.451. The interval for the higher dose is -136.4 to 4.759, with p = 0.068. These estimates should be distinguished from a documented prespecified analysis because the trial's own analysis plan is not reported in the registry record.

How should a confidence interval be understood?

General explanation: a confidence interval represents uncertainty around an estimate under the statistical model and its assumptions. It gives a range of values that are reasonably compatible with the observed data under that method; it is not a guarantee that the true value lies in the particular interval, and it does not show the probability that a particular result is true. In these comparisons, both intervals include zero, the value corresponding to no mean difference. Their widths also indicate that the estimates are imprecise: values on both sides of zero remain compatible with the reported data.

A confidence interval is useful alongside a point estimate because two studies can have similar estimates but very different precision. Here, the point estimates are negative, but the intervals extend across zero. That distinction prevents the point estimate from being read as if it were known without uncertainty. The intervals do not account for unknown features of the original analysis, such as any prespecified adjustment or missing-data method, because those details are not reported in the registry record.

What does a p-value add?

General explanation: a p-value measures how unusual data at least as discrepant as the observed data would be under a specified null model and statistical assumptions. It is not the probability that the null hypothesis is true, nor does it describe the size or clinical importance of an effect. The posted values are unadjusted p-values, and no multiplicity procedure is reported. They should therefore be read as unadjusted measures for the two listed contrasts, not as evidence that all sources of uncertainty or all comparisons have been accounted for.

The registry does not report whether a particular threshold for interpretation was specified in the original analysis plan. The planning illustration separately states a two-sided significance level of 0.05, but this is an assumption for the sample-size illustration, not confirmation of the trial's own analysis rule. It would be inappropriate to treat that planning assumption as proof of a prespecified testing procedure.

Why does variability matter?

The standard deviations are 85.9 for the lower-dose group, 91.0 for the higher-dose group, and 102.8 for placebo. General explanation: when participant outcomes vary widely, group means can be estimated less precisely, particularly when groups are small. This is reflected in uncertainty around the mean differences. Over-dispersion refers generally to variability greater than a model expects; where it occurs, model-based standard errors and intervals can be too optimistic unless the analysis accommodates it. The registry record does not report a model diagnostic or an over-dispersion assessment, so there is no basis to claim that a specific correction was needed or used in this trial.

The arm summaries list 15 participants for IMO-3100 at 0.16 mg/kg, 14 for IMO-3100 at 0.32 mg/kg, and 15 for placebo. Small groups provide limited information about the spread and shape of outcome distributions. The reported means and standard deviations are useful summaries, but cannot show the extent of skewness, outliers, or differences among participant subgroups. The exact number contributing to each endpoint summary and the approach to missing measurements are not reported in the registry record.

What do the analysis population and design tell us?

The registry labels the primary endpoint population as ITT. In general, an intention-to-treat approach aims to analyze participants according to their randomized groups, regardless of treatment adherence, but the label alone does not specify the exact implementation. The record does not report the analysis population details, exclusions, imputation method, or how participants with unavailable measurements were handled. Randomization, parallel groups, placebo control, and quadruple masking are recorded, but the randomization procedure, allocation concealment, and masking roles are not described.

Finally, the displayed pairwise contrasts are not adjusted for multiplicity according to the posted values. General explanation: when more than one statistical comparison is made, the chance of at least one apparently unusual result can increase, depending on the testing strategy and dependence among tests. A prespecified analysis plan may address this issue, but that plan and any adjustment are not reported in the registry record. The safest reading is therefore descriptive: the means, standard deviations, and recalculated unadjusted contrasts characterize the posted summaries, while the missing analytic details limit stronger inference.

10. Confidence Intervals and Precision

Precision concerns how tightly the data locate an estimated mean difference. The lower-dose comparison with placebo is -26.1, with a confidence interval from -93.89 to 41.69. The higher-dose comparison is -65.8, with a confidence interval from -136.4 to 4.759. Each interval includes zero, so the posted summaries are compatible with no mean difference as well as with differences in either direction within the respective interval. This does not make the estimates identical; it means the data do not locate either contrast precisely enough to exclude zero under the recalculated method.

The intervals are broad relative to their point estimates. For the lower dose, the interval extends well below and above the estimate. For the higher dose, it spans a substantial range of negative values and extends slightly above zero. A point estimate is the center of the reported comparison, but it should not be treated as a precise measure of the underlying difference when the interval is this uncertain. The estimates also do not establish which dose has the larger effect, because the registry does not report a direct comparison of the two doses.

General explanation: confidence intervals reflect sampling uncertainty under a statistical method and assumptions; they do not include every source of uncertainty. Their interpretation can depend on the analysis population, missing-data handling, outcome distribution, and whether multiple comparisons were considered. The registry record does not report the original analysis plan or missing-data methods, and the posted comparisons are unadjusted recalculations from summary statistics. Those limitations matter when interpreting the apparent precision. The intervals describe uncertainty in the listed comparisons, not certainty about clinical importance, which is not defined in the registry record.

11. 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 for 80% power and participants per arm for 90% power. They are not total event counts. The illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as its starting point and considers detecting 100%, 75%, or 50% of that observed effect. The trial's own original sample-size assumptions and justification are not reported in the registry record.

For the comparison of IMO-3100 at 0.16 mg/kg with placebo, planning for 100% of the observed effect gives 207 participants per arm for 80% power and 277 participants per arm for 90% power. Planning for 75% gives 368 and 493 participants per arm, respectively; planning for 50% gives 828 and 1,108 participants per arm. For IMO-3100 at 0.32 mg/kg versus placebo, the corresponding figures are 35 and 46 participants per arm for 100% of the observed effect, 62 and 82 for 75%, and 138 and 184 for 50%.

In plain terms, the 80% column describes the number of participants per arm that the illustration estimates would give an 80% chance of detecting the assumed effect under its stated assumptions. The 90% column applies the higher power target, which generally requires more participants. Smaller effects require more participants to distinguish them from random variation, as reflected by the larger figures for planning for 75% or 50% of the observed effect. These are planning illustrations based on the observed trial estimates, not observed power. The record does not report the trial's original design assumptions, so these figures should not be read as evidence about how enrollment of 44 was selected.

12. 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 = -26.100; pooled standard deviation σ = 94.728.
2. n = 2 × (1.96 + 0.842)² × 94.728² / -26.100² = 206.8, rounded up to 207 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 <- -26.1                      # observed difference in means
sigma <- 94.7276358830938                     # 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(1622348)
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 = 207 (80% power), 277 (90% power)
 75% of observed effect: n per arm = 368 (80% power), 493 (90% power)
 50% of observed effect: n per arm = 828 (80% power), 1,108 (90% power)
power.t.test: 207.7 
Simulated power at n = 207 per arm: 0.796 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry posts one primary outcome measure and no secondary outcome measures. It also lists two comparisons, one for each IMO-3100 dose versus placebo. The pairwise p-values are described as unadjusted. The registry record does not report whether these comparisons were prespecified as a family, whether another testing hierarchy was used, or whether any multiplicity adjustment was applied in the trial's own analysis. Without that information, the unadjusted p-values should not be interpreted as controlling the chance of a false-positive finding across all analyses that may have been planned or conducted.

The record identifies the primary endpoint population as ITT. That label communicates an intended analysis population, but it does not provide a full account of which randomized participants contributed to each result or how deviations from the assigned treatment were handled. The arm summaries list 15 participants for IMO-3100 at 0.16 mg/kg, 14 for IMO-3100 at 0.32 mg/kg, and 15 for placebo. The registry does not separately state the analyzed count for each endpoint summary or comparison.

Missing-data handling is not reported in the registry record. There is no reported account of the amount or reasons for missing endpoint measurements, or whether missing values were excluded, imputed, or addressed in another way. General explanation: missingness can affect estimates if the likelihood of an unavailable measurement is related to participant outcomes or treatment group. Different analytic choices can also produce different uncertainty estimates. The record does not support an assessment of whether missing data influenced these findings.

The original statistical analysis plan, prespecified model, and analysis population rules are not reported in the registry record. As a result, the recalculated comparisons from posted summaries should be understood as unadjusted statistical descriptions rather than confirmation of the trial's planned inferential analysis. The record also does not report interim analyses or stopping rules. Their absence from the registry record is not evidence that a particular procedure was or was not used; it means those details cannot be evaluated from the posted information.

14. 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 non-serious adverse event terms

The registry reports no participants affected by serious adverse events in any of the three groups: 0 of 15 for IMO-3100 at 0.16 mg/kg, 0 of 14 for IMO-3100 at 0.32 mg/kg, and 0 of 15 for placebo. It also reports 0 deaths in each group. No serious adverse-event terms are listed. These are counts recorded during the trial, not evidence that serious events are impossible or that the groups have identical risks.

For other adverse events, the record lists 6 of 15 participants in the 0.16 mg/kg group, 8 of 14 in the 0.32 mg/kg group, and 4 of 15 in the placebo group as affected. These are participant counts, rather than a detailed account of the number, duration, severity, or relationship of each event. The registry record does not provide the specific other adverse-event terms in the information posted for this analysis, nor does it report event-level details or statistical comparisons.

Small groups and the limited reporting mean that these figures should be read descriptively. The counts do not establish whether observed events were caused by treatment, and they do not provide a complete assessment of comparative safety. The registry record does not report further details about adverse-event collection, attribution, or follow-up.

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

The results describe an early-phase randomized comparison of two IMO-3100 dose levels with placebo on change in mean epidermal thickness of an index lesion. The active-group mean changes were negative, while the placebo mean change was positive. The posted comparisons also have negative point estimates, meaning the active-group average changes were lower than the placebo average changes in these summaries. These statements describe the recorded endpoint; they do not establish the clinical importance of the changes.

The uncertainty is substantial. The confidence interval for each comparison includes zero, and the standard deviations are large relative to the arm means. The higher-dose estimate is more negative than the lower-dose estimate, but the record does not report a direct statistical comparison between doses, and both placebo comparisons are imprecise. The posted results therefore do not establish a dose-response relationship or a definitive difference from placebo.

The record reports one primary outcome and no secondary outcomes. It does not provide patient-reported outcomes, longer-term results, detailed endpoint collection procedures, or a threshold for a clinically meaningful change. The endpoint timeframe is listed as 8 weeks, while the trial title describes a 4-week trial; further timing details are not reported in the registry record. These results should not be generalized to outcomes or time periods that were not posted.

The comparisons are unadjusted recalculations from arm-level summary statistics, and no sponsor analyses are listed. The original statistical plan, handling of missing outcome data, multiplicity procedures, and exact analysis counts are not reported in the registry record. These gaps limit how confidently the numerical comparisons can be interpreted as the trial's planned inferential results.

In general, a trial's observed means and uncertainty intervals answer a narrower question than whether an intervention is appropriate for an individual. The registry results alone do not establish that either dose is beneficial, ineffective, or safe for any particular person. They describe the posted group-level measurements and their uncertainty in this completed phase 2 trial.

16. Why This Trial Matters Statistically

This trial illustrates why an estimate and its precision should be read together. The arm means differ in direction from placebo, and the two recalculated mean differences are negative. Yet each confidence interval includes zero and spans a wide range of values. Looking only at the point estimates would obscure how uncertain the comparisons are; looking only at whether an interval includes zero would obscure the magnitude and direction of the estimates. Both pieces of information matter for a statistical reading.

The arm-level standard deviations are large, while each group contains a limited number of participants. General statistical principle: high variability and small groups make it harder to distinguish a true group difference from sampling variation. The posted results demonstrate the practical consequence through broad intervals around the contrasts. The record does not contain individual participant data, so the role of outliers or the distribution of changes cannot be evaluated.

The trial also highlights the distinction between a planning illustration and a trial's original sample-size design. The planning figures use observed effects and specified assumptions, while the original justification is not reported in the registry record. Such illustrative calculations can show how planned sample sizes depend on the effect one aims to detect, but they cannot establish what design assumptions were made before the trial or explain the enrollment decision.

Finally, reporting completeness is itself relevant to interpretation. The registry identifies an ITT endpoint population and posts arm summaries, but does not report detailed missing-data methods, multiplicity procedures, or the original analysis plan. Statistical interpretation depends not only on numerical estimates but also on knowing how those estimates were generated. This record therefore provides useful descriptive results while leaving important inferential and design questions unresolved.

17. 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 posted endpoint results are based on small arm sizes: 15 participants for IMO-3100 at 0.16 mg/kg, 14 for IMO-3100 at 0.32 mg/kg, and 15 for placebo. The standard deviations are 85.9, 91.0, and 102.8, respectively. The broad confidence intervals around the recalculated mean differences indicate limited precision. Individual data are not posted, so the distributions, outliers, and influence of any particular observations cannot be assessed.

The registry record lists one outcome measure and no secondary outcome measures. It does not report the original analysis plan, model specification, randomization procedure, allocation concealment, or the analysis details behind the ITT designation. The pairwise comparisons are unadjusted recalculations from summary statistics, and no sponsor analyses are listed. Missing endpoint data, their reasons, and their handling are not reported. Multiplicity procedures and interim analyses are also not reported in the registry record.

The endpoint is a measured change in epidermal thickness, but the registry does not define a clinically important difference or describe the relationship between this measurement and outcomes important to participants. The timing is recorded as 8 weeks, while the official title describes a 4-week trial; further clarification of the endpoint schedule is not reported in the registry record. The record does not provide longer-term results or posted secondary outcomes that could address other dimensions of psoriasis or treatment effects.

Safety reporting is limited to group counts for serious events, other adverse events, and deaths. Specific details for other adverse events, severity, attribution, and event timing are not reported in the registry record. The absence of serious adverse events in these groups is a descriptive observation in a small trial and cannot resolve uncommon risks. Taken together, these limitations restrict the results to an uncertain, short-term group comparison of the recorded continuous endpoint.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Trial of IMO-3100 in Patients With Moderate to Severe Plaque Psoriasis — NCT01622348.
• Registry record last updated 2018-01-09; status last verified 2017-12.
• Results first posted 2017-11-13.
• 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.

21. Record Summary

NCT01622348 is a completed randomized, double-blind, placebo-controlled, parallel phase 2 trial of IMO-3100 in patients with moderate to severe plaque psoriasis. The registry lists quadruple masking and enrollment of 44. Treatment groups received IMO-3100 at 0.16 mg/kg, IMO-3100 at 0.32 mg/kg, or saline for injection as placebo. The primary outcome was mean change from pretreatment baseline to end-of-treatment in epidermal thickness of the index lesion, measured in millimeters, with an 8-week timeframe and an ITT population.

Mean changes were -8.8, -48.5, and 17.3 in the lower-dose, higher-dose, and placebo groups, respectively. The recalculated unadjusted mean differences versus placebo were -26.1 and -65.8; both confidence intervals include zero. No participants were reported as affected by serious adverse events, and deaths were 0 in all groups. The registry record does not report the original statistical plan, missing-data methods, multiplicity procedures, or a clinical threshold for interpreting the endpoint.