Multiple-loading Dose Regimen Study in Patients With Chronic Plaque-type Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multiple-loading Dose Regimen Study in Patients With Chronic Plaque-type Psoriasis (NCT00805480), a randomized phase 2 study. The primary outcome is Change From Baseline in Psoriasis Area and Severity Index (PASI) Scores.

2. Clinical Question

3. Trial Design

This was a phase II randomized, double-blind, multicenter, parallel-group, placebo-controlled study of AIN457 in chronic plaque psoriasis. The registry describes the trial as a four-arm study of single and multiple doses, with safety, efficacy and duration of response among its stated aims. Enrollment was 130. The sponsor was Novartis Pharmaceuticals. The study started in 2008-12, had primary completion in 2010-09 and is listed as completed.

The four assigned groups were AIN457 3 mg/kg, AIN457 10 mg/kg, AIN457 10 mg/kg x3, and placebo. In the first two active groups, the named AIN457 dose was given on day 1, with matching placebo on days 15 and 29. The arm description for AIN457 10 mg/kg x3 instead says that participants received AIN457 3 mg/kg on days 1, 15 and 29. The registry record therefore contains an inconsistency between that arm's title and its dosing description; it does not clarify which is intended. The placebo group received matching placebo on all three days.

Randomization and double masking are stated in the record, but the randomization method, concealment procedures and masking details are not reported in the registry record. The allocation ratio is also not reported. The primary endpoint is a continuous measure, change from baseline in PASI score, assessed at baseline and Week 12. Three secondary outcomes are listed: PASI improvement thresholds and investigator global assessment categories. The registry lists five outcome measures overall, but the other outcome details are not set out in the registry record used for this analysis.

Although the study title and aims include duration of response, follow-up details for that aim are not reported in the registry record. The record also does not report a protocol-level sample-size justification or the statistical plan. The enrollment figure describes trial enrollment; it should not be treated as the number contributing to every endpoint. For the primary measure, the record specifically says that the analyzed groups included participants with both baseline and Week 12 values.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants from the PD Analysis Set, who had both baseline and week 12 values, were included in the analysis. As such, the population for each treatment group is different from the PD population in the participant flow. The PD analysis set included participants who had at least one dose of study medication and had no protocol deviations.

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 Psoriasis Area and Severity Index (PASI) Scores, measured over Baseline, Week 12.

The primary endpoint was change from baseline in the Psoriasis Area and Severity Index (PASI) score at Week 12. PASI combines assessments of affected skin area and lesion severity across the head, arms, trunk and legs. For each area, the assessment includes the percentage of skin involved and clinical signs that include erythema, induration and desquamation. Area-specific scores are weighted and combined into a single score.

The scale runs from 0, no disease, to 72, maximal disease. A change score describes how the measured score at follow-up differs from the baseline score; the registry reports a mean change for each treatment group. Negative values in the posted results indicate that the mean Week 12 score was lower than the mean baseline score in that group. The standard deviation describes variability in individual change scores within a group; it is not a confidence interval for the mean and does not by itself establish how precisely a treatment-group contrast is estimated.

PASI is used as a combined disease measure because it captures both the extent of affected skin and assessed lesion severity rather than relying on only one component. The registry also lists percentage-improvement thresholds and investigator global assessment categories as secondary outcomes. Those measures provide different ways to classify response, but the primary result is the continuous mean change in PASI. The record does not provide a direct two-arm estimate for comparing that change between an AIN457 group and placebo.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent? The primary result is a mean of individual PASI change scores for participants included in each analysis group. In general, a change score is calculated for each participant by comparing the follow-up measure with the baseline measure, and the mean summarizes those individual changes. A negative mean indicates a lower follow-up score on this scale. The registry reports means and standard deviations, but it does not give participant-level data, adjusted estimates or an inferential comparison between each active group and placebo.

What does the standard deviation tell the reader? In general, a standard deviation describes how spread out individual observations are around their group mean. It is a measure of variability among participants, not a measure of uncertainty around a treatment difference. A confidence interval, by contrast, gives a range of values compatible with an estimate under a specified statistical procedure. The registry does not report confidence intervals for the primary group means or for treatment-versus-placebo contrasts in the registry record used. A standard deviation should therefore not be interpreted as though it were an interval for the mean or as evidence of statistical significance.

Why are within-group changes not the same as treatment effects? General statistical reasoning distinguishes change over time within one group from the contrast between groups assigned to different conditions. Participants can have changing scores for reasons other than the assigned intervention, including the natural course of the condition and factors shared across study groups. Randomization is intended to support comparisons between assigned groups, but the relevant estimate is a between-group contrast. The means in the registry are group-specific change summaries; the record does not report an estimable two-arm continuous comparison. No unadjusted calculation from those summaries is presented as a replacement for the sponsor’s analysis.

What does randomization contribute? In general, random assignment can reduce systematic differences between groups at the start of a trial, making a properly conducted between-group comparison more informative about an intervention than a simple before-and-after comparison. The registry identifies this study as randomized and double-blind, but it does not report the sequence-generation method, allocation concealment procedures or details of the masking. Those implementation details are therefore not available for evaluating how randomization and masking were carried out.

Why does the analysis population matter? The primary outcome description restricts analysis to participants in the PD Analysis Set who had both baseline and Week 12 values. The registry also states that the treatment-group analysis populations differ from the PD population in participant flow. General statistical reasoning is that restricting an analysis to participants with observed values can affect estimates if having a measured outcome is related to the outcome itself or to treatment assignment. The record does not give enough detail to assess whether missingness was related to these factors, what methods were used to handle missing data, or whether sensitivity analyses were performed.

How should small or unequal analysis groups be considered? In general, estimates from smaller groups tend to be less precise than estimates from larger groups, all else being equal. The primary analysis counts differ across the four groups, and the placebo analysis includes 5 participants. This observation does not justify calculating new precision estimates from the published summaries. It does mean that the placebo mean and its standard deviation should be read as summaries of the analyzed participants rather than as highly precise estimates of the group’s broader outcome distribution. The registry does not report a confidence interval that would quantify uncertainty for a treatment contrast.

What does the registry say about statistical testing? The record does not provide a model description, covariate adjustment details, hypothesis-testing procedure, alpha allocation, or a prespecified testing hierarchy. It identifies no estimable two-arm comparison for the continuous primary endpoint in the posted results. The analysis count is listed as zero, and no p-values or confidence intervals for a primary treatment contrast are included in the registry record used. These omissions do not show that no analysis was conducted outside the posted record; they mean that the registry record does not report those details in the material available for this analysis.

Why does over-dispersion matter in some settings? General explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. It matters particularly for count outcomes, where a model that assumes too little variability can produce intervals that are too narrow and tests that are too optimistic. The primary endpoint in this study is continuous, and the record reports standard deviations rather than a count model. Over-dispersion is therefore not a specific reported feature of this primary analysis.

What can sample-size calculations show? General explanation: a planning calculation can illustrate how many participants might be needed under stated assumptions to detect a chosen effect with a chosen power and significance level. It is a design illustration, not observed power and not evidence that the trial detected an effect. The registry record does not report its own sample-size justification or protocol assumptions. No numerical planning estimates are stated in the registry record used for this interpretation, so none are reproduced.

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("AIN457 3 mg/kg", "AIN457 10 mg/kg", "AIN457 10 mg/kg x3", "Placebo")
n   <- c(27, 23, 27, 5)
m   <- c(-12.46, -13.35, -18.02, -4.18)
sp  <- c(7.668, 6.195, 6.792, 4.698)
sd  <- sp      # posted standard deviations
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  AIN457 3 mg/kg  27  -12.460  7.668  -15.493  -9.427
CARM  AIN457 10 mg/kg  23  -13.350  6.195  -16.029  -10.671
CARM  AIN457 10 mg/kg x3  27  -18.020  6.792  -20.707  -15.333
CARM  Placebo  5  -4.180  4.698  -10.013  1.653

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes: the percentage of participants with at least 50% PASI improvement from baseline, the percentage with at least 75% or 90% improvement, and the percentage in each investigator global assessment category. It lists five outcome measures overall. The testing hierarchy, any multiplicity adjustment, and the statistical plan for handling multiple endpoints or comparisons are not reported in the registry record. Without those details, the secondary outcomes should be treated as separate reported measures rather than as a documented family of confirmatory tests. No conclusion about control of false-positive findings can be drawn from the outcome list alone.

For the primary PASI change result, the registry says participants had to be in the PD Analysis Set and have both baseline and Week 12 values. It also notes that each treatment group’s analyzed population differed from the PD population in participant flow. The complete PD Analysis Set definition is not reported in the registry record; the description ends before giving a complete eligibility definition. The missing-data method, reasons for missing values, and any sensitivity analyses are also not reported in the registry record.

These details matter because an analysis limited to participants with observed values may differ from an analysis of all randomized participants, particularly if missing outcome data are associated with treatment assignment or participants’ outcomes. The posted group counts describe those contributing to the primary measure, not necessarily everyone randomized. The record does not provide enough information to determine the implications of missing values for the means or for a comparison between groups.

The registry reports no estimable two-arm comparison for the continuous primary endpoint and lists no analysis count. A prespecified testing strategy, interim analysis plan and treatment of multiplicity are not reported in the registry record. The absence of those details in the registry entry should not be interpreted as proof that the trial had no such procedures; it means their use cannot be assessed from this record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina pectoris (3.4%), myocardial infarction (3.4%), psoriasis (3.4%), pancreatitis (3.3%), fibula fracture (3.3%).

The registry reports serious adverse events by group as affected participants and participants at risk. For AIN457 3 mg/kg, 2 of 30 participants at risk were affected; for AIN457 10 mg/kg, 3 of 29; for AIN457 10 mg/kg x3, 2 of 31; and for placebo, 0 of 10. These are registry counts. The record does not provide a statistical comparison of serious adverse event frequency between groups, and the arm-label inconsistency for AIN457 10 mg/kg x3 also applies when interpreting that group’s assigned regimen.

For the separate “other” adverse-event category, the reported figures were 15 of 30, 22 of 29, 19 of 31 and 3 of 10, respectively, in the same group order. The registry does not define further in the registry entries what is included in this category. These counts should not be reclassified or treated as a causal comparison.

The listed serious-event terms and percentages are angina pectoris, 3.4%; myocardial infarction, 3.4%; psoriasis, 3.4%; pancreatitis, 3.3%; fibula fracture, 3.3%; and tibia fracture, 3.3%. The record does not attribute these listed percentages to specific treatment groups in the registry record used. Death counts are not reported in the registry record. Adverse-event counts describe events recorded during the trial; without further detail on definitions, timing, severity and group-specific attribution, they do not by themselves establish whether an event was caused by treatment.

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

The primary endpoint is a continuous score intended to summarize affected skin area and lesion severity. The posted group means indicate that mean PASI scores decreased from baseline to Week 12 in each analyzed group, including placebo. This is a description of the observed changes among participants with the required values in the stated analysis population. It is not, by itself, evidence of how much change was attributable to assignment to an AIN457 regimen rather than to other influences.

A direct treatment interpretation depends on a comparison with the randomized placebo group and on the uncertainty around that contrast. The registry results do not provide an estimable two-arm comparison for this continuous outcome, and the registry entries do not include a confidence interval or p-value for such a comparison. The group means and standard deviations should not be used to imply a treatment difference or statistical significance that the record does not report.

The analyzed groups have different counts, and the placebo primary analysis includes 5 participants. The record’s requirement for both baseline and Week 12 values means that the endpoint summaries are not necessarily summaries of everyone enrolled or randomized. The registry does not report enough information to evaluate how missing outcome values might affect the findings. In addition, the dosing description for the group labelled AIN457 10 mg/kg x3 specifies 3 mg/kg on three days, so the regimen represented by that group is uncertain from the registry wording.

The safety counts describe serious and other adverse events as recorded by group, but the registry does not provide a comparative statistical analysis or group attribution for the listed serious-event terms. These figures are descriptive and should not be taken as proof of safety or harm. More broadly, the registry entry presents group-level endpoint and adverse-event summaries, while important details about the analysis, missing data, and the precision of treatment contrasts are not reported in the registry record. The results therefore support a careful account of what was recorded, not a definitive causal conclusion about an individual regimen.

14. Why This Trial Matters Statistically

This trial illustrates why an endpoint’s scale and direction need to be understood before group means are interpreted. PASI combines affected area and lesion severity, and lower scores indicate less measured disease burden on the stated scale. Because the posted outcome is change from baseline, negative group means describe decreases in the score. That meaning is distinct from the question of whether the change differs between randomized groups.

It also demonstrates the importance of separating within-group summaries from comparative estimates. A mean change in an active group and a mean change in placebo are not themselves a reported treatment-effect estimate. The registry does not provide an estimable two-arm comparison for the continuous primary endpoint, so readers cannot assess a reported between-group effect and its precision from the posted results. Standard deviations describe participant-level spread; they do not substitute for confidence intervals around a contrast.

The record also highlights how analysis populations affect interpretation. The primary endpoint includes only participants with baseline and Week 12 values in the PD Analysis Set, and the analysis populations differ from the PD population in participant flow. The registry’s incomplete description of that set and absence of missing-data methods limit assessment of how representative the endpoint groups are.

Finally, consistency in intervention descriptions is essential to interpreting randomized evidence. The title and dosing description for the AIN457 10 mg/kg x3 arm do not match. That ambiguity makes it difficult to connect the arm’s observed mean change to a specific dosing schedule. Together, these issues show that numerical summaries are most informative when accompanied by clear treatment definitions, complete analysis populations, and comparative estimates with uncertainty.

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.

Several trial-specific limitations constrain interpretation of the posted results. First, the registry does not report an estimable two-arm comparison for the continuous primary endpoint. The reported group means therefore do not provide a direct estimate of how the AIN457 regimens differed from placebo, and no confidence interval or p-value for such a contrast is included in the registry record used.

Second, the primary analysis used participants in the PD Analysis Set with both baseline and Week 12 values. The record says group analysis populations differed from the PD population in participant flow, but the complete PD definition, the number and reasons for missing values, and the approach to missing data are not reported in the registry record. This limits assessment of selection into the analyzed groups and the robustness of the endpoint summaries.

Third, the primary endpoint count for placebo is 5, while the active-group counts are 27, 23 and 27. The record does not explain the difference between these analysis counts or provide uncertainty estimates for the comparisons. The placebo summary should therefore be read as a descriptive result for the participants included, not as a precise estimate of a comparative effect.

Fourth, the AIN457 10 mg/kg x3 arm label conflicts with its dosing description, which specifies AIN457 3 mg/kg on days 1, 15 and 29. The registry record does not resolve the inconsistency. The statistical methods, sample-size justification, multiplicity procedures, interim analyses and handling of missing data are also not reported in the registry record. These omissions limit independent assessment of the planned analyses and the meaning of the posted summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multiple-loading Dose Regimen Study in Patients With Chronic Plaque-type Psoriasis — NCT00805480.
• Registry record last updated 2015-02-10; status last verified 2015-01.
• Results first posted 2015-02-10.
• 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

NCT00805480 is a completed phase II randomized, double-blind, multicenter, parallel-group, placebo-controlled study sponsored by Novartis Pharmaceuticals. It enrolled 130 participants with chronic plaque psoriasis and compared three AIN457-labelled regimens with placebo. The study started in 2008-12 and primary completion was in 2010-09.

The primary endpoint was mean change from baseline to Week 12 in PASI score. The posted mean changes were -12.46 for AIN457 3 mg/kg, -13.35 for AIN457 10 mg/kg, -18.02 for the group labelled AIN457 10 mg/kg x3, and -4.18 for placebo. These are group summaries, not a reported treatment-versus-placebo contrast. The registry does not report an estimable two-arm comparison for this continuous endpoint. The primary analysis included participants in the PD Analysis Set with both baseline and Week 12 values; full analysis and missing-data details are not reported in the registry record. The record also contains an unresolved inconsistency between the label and dosing description for the AIN457 10 mg/kg x3 group.