Study of Alwextin® Cream in Treating Epidermolysis Bullosa: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Alwextin® Cream in Treating Epidermolysis Bullosa (NCT00825565), a na phase 2 study. The primary outcome is Physician Assessment of Individual Signs.

2. Clinical Question

The study asked whether applying allantoin 3% cream, called Alwextin, was safe and effective in improving the healing of recurrent skin lesions and reducing overall blistering in people with epidermolysis bullosa (EB). The cream was applied topically to the entire body once daily. The primary outcome described in the registry record was a physician assessment of signs associated with EB, measured at baseline and at 12 weeks.

This was an open-label pilot study with one treatment group and no control group. Its design can describe what was recorded among people who used the cream, but it cannot by itself separate changes during the study from changes that might have occurred without the cream. The registry record does not report the primary outcome values, so it is not possible to describe whether the physician assessments changed over time or how large any change was.

Because the primary results are absent, the clinical question can be described from the study objectives and endpoint definition, but cannot be answered from the posted results. The available record supports describing enrollment, completion, the assessment plan, and adverse-event counts—not estimating a treatment effect.

3. Trial Design

This completed Phase 2 study is titled “Study of Alwextin® Cream in Treating Epidermolysis Bullosa.” Its official title describes it as an open-label pilot study investigating the safety and tolerability of Alwextin 3.0% cream in treating EB. Northwestern University is listed as the sponsor. The study began in 2009-02, and primary completion is listed as 2010-11.

The study had a single group, with eight subjects enrolled. The arm description states that all eight completed the study. The intervention was Alwextin cream, classified as a drug. The study was open-label, with masking listed as none; allocation is listed as not applicable. There was no randomized or concurrent control group, so the enrolled participants do not provide a like-for-like comparison against an untreated or alternative-treatment group.

The study objective included safety and effectiveness in improving healing of recurrent skin lesions and reducing overall blistering. The cream was applied topically to the entire body once daily. The registry describes a primary physician assessment at baseline and at 12 weeks. Its primary-outcome population wording refers to subjects who used cream on the entire body for the entire month. The number of participants meeting that analysis-population description is not reported in the registry record.

The registry lists four outcome measures, but the primary endpoint results and the other outcome results are not reported in the registry record. It also lists no analyses. Details such as a prespecified statistical analysis plan, sample-size justification, interim analyses, and procedures for handling deviations from the treatment regimen are not reported in the registry record. Those omissions prevent a fuller reconstruction of how the study was intended to translate observations into statistical conclusions.

The small pilot design is suited to documenting what was observed in this group and to describing study conduct. Without a comparator, randomization, masking, and reported outcome estimates, it does not establish whether changes over time were caused by the cream. Completion by all eight enrolled subjects is a study-flow fact; it does not fill in the missing endpoint results or show that all eight were included in the primary analysis.

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: Subjects were instructed to discontinue use of allantoin 1.5% cream (Alwyn) for at least 30 days prior to initiating the study medication, allantoin 3% cream (Alwextin).

Overall Study

Analysis population for the primary outcome, as defined in the registry: Subjects who used allantoin 3% cream for an entire month prior to the BSA monthly assessment were included in the analysis.

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 Physician Assessment of Individual Signs, measured over baseline and at 12 weeks.

The primary endpoint is titled “Physician Assessment of Individual Signs.” It is expressed in participants, and the registry identifies its measure as a count of participants. Assessments were planned at baseline and at 12 weeks.

The assessment covers blistering and erosions; oozing, weeping, and crusting; pruritis; erythema on unblistered surrounding skin; pain; and milia. Each sign is evaluated across four body areas: head/neck, upper limbs, trunk, and lower limbs. The listed rating scale runs from 0, clear, to 4, severe, with intermediate categories of almost clear, mild, and moderate.

This type of clinician assessment is intended to describe signs that may be present in different parts of the body, rather than relying on a single symptom or location. Considering several signs and body areas can capture a broader clinical picture of EB. The registry notes that signs may vary depending on the body area assessed. That makes clear definitions and consistent assessments important when interpreting changes over time.

The registry’s endpoint description does not explain how the individual sign scores were combined into a participant-level count, what threshold defined a participant as having an outcome, or how changes from baseline were summarized. These details are not reported in the registry record. The primary endpoint’s numerical results are also not reported, so the assessments’ distribution, any change between visits, and precision of an estimated change cannot be described.

The primary-outcome population is described as participants who used cream on the entire body for the entire month. The record does not state how many participants met this condition. This matters because the eight enrolled and completed participants cannot automatically be assumed to be the same as the endpoint analysis population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes the study as open-label and single-group, with allocation not applicable and masking none. It lists no analyses. The numerical primary outcome results, the statistical methods applied to that outcome, and a prespecified analysis plan are not reported in the registry record. The explanations below distinguish general statistical concepts from information specific to this study.

What can a single-group design estimate?

In general, a single-group study can describe measurements collected among participants who receive an intervention. If repeated measurements are reported, it can also describe within-person changes over time. Those descriptions do not, on their own, estimate what would have happened to the same participants without the intervention. A concurrent control group helps estimate that counterfactual comparison, while random allocation can reduce systematic differences between groups. Neither a control group nor random allocation is described for this study.

Here, the registry gives the assessment times and the outcome definition, but not the participant-level counts or summaries needed to describe a change. A comparison of baseline with 12 weeks cannot be reconstructed from the information in the registry record. No treatment-effect estimate or uncertainty interval is reported there.

What does an open-label assessment imply?

In general, open-label means treatment assignment is not concealed from those involved in the study. For outcomes involving physician judgment, knowledge that participants received the study cream may be relevant to how assessments are made or interpreted. This is a potential design consideration, not evidence that any particular assessment was influenced. The registry identifies a physician assessment but does not report procedures for assessor training, independent review, or masking of outcome assessors.

More broadly, repeated assessments can vary because of actual changes in signs and because of measurement variability. Consistent definitions and assessment procedures help make measurements comparable. The record describes the signs, body areas, rating categories, and timepoints, but it does not report additional details on assessor reliability or how scores across signs and areas were combined.

How should the endpoint scale be understood?

In general, the listed ratings are ordered categories: clear, almost clear, mild, moderate, and severe. An ordered scale communicates rank, but it does not automatically mean that the distance between each adjacent category is equal. Treating such ratings as numerical values in a statistical model can require assumptions about how those categories relate to one another. The registry record does not state whether the individual ratings were analyzed as ordered categories, converted to counts, or combined in another way.

The endpoint is identified as a count of participants, yet the description also specifies ratings for several signs in multiple body areas. A participant-level rule is therefore important for interpreting the count: for example, a report would need to clarify what score or change qualifies a participant for inclusion in that count. The rule used is not reported in the registry record. No additional rule should be inferred from the scale description alone.

What does statistical precision mean?

In general, a confidence interval is a range of values that expresses the statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that includes values representing little or no change may leave uncertainty about the direction or magnitude of an effect. A p-value addresses compatibility of data with a specified statistical model and null hypothesis; it does not measure clinical importance or the probability that a treatment works.

No confidence interval, p-value, or primary-outcome estimate is reported in the registry record. Consequently, statistical precision for the primary endpoint cannot be assessed. General explanations of these tools do not substitute for an estimate and its uncertainty from the study.

What is the role of the planning illustration?

The record describes a planning illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For outcomes other than time-to-event outcomes, the stated output convention is participants per arm; time-to-event calculations are described in terms of total events. These are planning assumptions, not evidence that the trial was designed as a two-arm study. The actual study had one group.

In general, a sample-size calculation estimates how many participants a hypothetical design might require under specified assumptions. Such a calculation is not an observed result and is not “observed power.” A calculation based on an estimated effect also inherits uncertainty in that estimate. No numerical planning outputs or observed primary effect are reported in the registry record, so no planning figure or effect size can be interpreted from this record alone. The trial’s own sample-size justification is not reported in the registry record.

Over-dispersion is a general concern when counts vary more widely than a chosen statistical model expects. If present, a model that assumes less variability than the data contain can understate uncertainty. The registry record does not report an analysis model or dispersion estimate, so it is not possible to determine whether this issue applied to the primary endpoint.

Why does a sponsor analysis matter?

When sponsor-reported analyses and simple recalculations from posted summary statistics differ, the sponsor’s own analysis takes precedence for describing the reported trial result. Recalculations from summary statistics are unadjusted and may not reproduce a prespecified analysis, which could account for covariates, repeated measurements, or other design details. The registry record lists no analyses and no primary outcome summaries, so there is no reported sponsor analysis or recalculated primary estimate to compare.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, but the primary measure is the only one described in detail in the record summarized by these results. Results for the primary endpoint and the other outcome measures are not reported in the registry record. The number of analyses is listed as zero. A statistical analysis plan, any hierarchy for testing outcomes, and any adjustment for multiple comparisons are not reported in the registry record.

Multiplicity is a general issue that arises when several outcomes, timepoints, subgroups, or statistical tests are examined. The more tests conducted, the greater the chance of finding an apparently notable result by chance if all tests are interpreted without accounting for their number. Prespecified outcome priorities and analysis procedures can help readers distinguish confirmatory analyses from exploratory ones. Because the relevant analysis details and results are not reported, it is not possible to assess how multiplicity was handled in this study.

The record states that all eight enrolled subjects completed the study. Completion does not necessarily mean every scheduled assessment was available or included in an analysis. The primary-outcome population is described as people who used cream on the entire body for the entire month, but the number meeting that condition is not reported. The registry does not report the count of missing assessments, reasons for missing data, exclusions, or methods used to handle missing values.

In general, missing-data methods can affect estimates when observations are incomplete, particularly if missingness is related to health status or outcome values. The appropriate interpretation depends on how much information is missing and why. Since neither the completeness of the endpoint measurements nor the analysis method is described, the impact of missing data cannot be evaluated from the registry record. No specific assumption about missingness or analysis population should be inferred.

11. 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 non-serious adverse event terms

For the Allantoin 3% Cream group, eight participants were listed as at risk for serious adverse events, and zero were listed as affected. The registry also lists eight participants at risk for other adverse events and four affected. These are participant counts for the single treatment group; they are not comparisons against a control group.

A count of zero serious adverse events means that none were recorded as affected in this group in the posted safety information. It does not prove that the intervention cannot be associated with serious events. In general, a small group can provide limited information about uncommon events, and the absence of an event in a study does not establish the absence of risk. The registry lists no top serious adverse-event terms. The number of deaths is not reported in the registry record.

The four participants affected by other adverse events indicate that such events were recorded, but the registry information does not identify their terms, severity, timing, relationship to treatment, or whether any participant experienced more than one event. No conclusion about the nature or cause of those events can be drawn from the count alone.

These safety figures should be read as descriptive counts, not as proof of comparative safety. With no comparator arm, the figures do not show whether event occurrence differed from what would have been observed under another treatment or without the study cream. The registry’s safety counts also do not replace the missing primary efficacy results.

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

The record establishes that an open-label Phase 2 pilot study of Alwextin 3.0% cream enrolled eight people with EB, used a single treatment group, and recorded completion by all eight. It also describes a physician assessment of individual signs at baseline and 12 weeks, and reports adverse-event counts for the treatment group. These registry entries characterize study conduct and the information available in the registry.

The primary outcome results are not reported in the registry record. Therefore, the available record does not show whether physician-assessed signs changed, how many participants met any improvement criterion, or how precise an estimated change would be. It also does not provide reported results that answer the stated goals concerning healing of recurrent skin lesions or overall blistering. Lack of reported results should not be interpreted as evidence of no change or as evidence of benefit.

The study design also limits what any within-group change could establish. A single group without randomization or a control comparison cannot separate a treatment-associated change from natural variation, other care, or other influences. Open-label assessment may be relevant for outcomes involving clinical judgment, although the record does not establish that assessment bias occurred.

The safety counts report zero participants affected by serious adverse events and four affected by other adverse events among eight at risk. These figures are descriptive and do not establish comparative safety or exclude uncommon harms. The death count is not reported in the registry record.

In practical statistical terms, this record is informative about the pilot’s design, enrollment, completion, intended outcome assessment, and limited safety counts. It is not sufficient to estimate the primary outcome effect or to make a causal comparison. The missing outcome estimates, analysis details, and analysis-population counts leave substantial uncertainty about what the assessments showed.

13. Why This Trial Matters Statistically

This trial illustrates why a registry description and a registry result are not the same thing. The study objective and endpoint are described, and the record reports that eight participants enrolled and completed the study. Yet the primary endpoint values and statistical estimates are not reported. Without those results, readers cannot determine the direction, magnitude, or precision of any change in physician-assessed signs.

The design also makes the distinction between observation and causal inference especially important. A single-group pilot can record what happened among participants receiving the cream, but there is no concurrent control group to show what might have happened under a different condition. Randomization is not part of the design. Thus, even a reported before-and-after change would need cautious interpretation as an observed trajectory rather than a controlled treatment effect.

The endpoint itself demonstrates another statistical issue: a count of participants depends on how individual assessments are translated into a participant-level outcome. The record names multiple signs, body areas, ordered severity categories, and two assessment times. It does not report the rule used to combine those components or the resulting participant counts. Clear endpoint definitions and transparent analysis rules are necessary for readers to understand what a numerical result represents.

Finally, the safety counts show how small pilots can describe events without resolving broader safety questions. Zero serious adverse events were recorded among eight participants at risk, while four were affected by other adverse events. Those observations are useful context, but they do not provide a controlled estimate of comparative risk. Overall, the study’s statistical importance lies in clarifying which information is present and which conclusions remain unsupported by the registry record.

14. 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 that the registry record does not report the primary endpoint results. It gives the assessment description and timepoints, but not scores, participant counts for the endpoint, changes, or uncertainty estimates. Results for the other listed outcome measures are also not reported in the registry record. This prevents quantitative interpretation of the study’s stated clinical objectives.

The study included one group and had no randomized comparator. Consequently, it cannot provide a controlled estimate of the effect attributable to the cream. Its open-label nature is an additional consideration for a physician-rated endpoint, though the registry does not report whether assessors knew treatment status or how assessments were standardized beyond the stated scale description.

Although all eight enrolled subjects completed the study, the primary analysis population is described more narrowly as subjects who used cream on the entire body for the entire month. The number meeting that condition is not reported. The registry also does not report whether all eight had complete baseline and 12-week assessments, whether any observations were excluded, or how missing data were handled.

The endpoint description includes multiple signs and body areas but does not report how those assessments were combined into the stated participant count, what threshold defined an endpoint event, or what statistical model was used. A statistical analysis plan, sample-size justification, interim analyses, multiplicity procedures, and model diagnostics are not reported in the registry record. Therefore, the planned and actual statistical approaches cannot be fully evaluated.

The safety record provides counts but not the terms or clinical details of other adverse events. It lists no serious adverse-event terms, and the number of deaths is not reported. The small single-group sample and lack of comparator further limit interpretation of these safety observations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Alwextin® Cream in Treating Epidermolysis Bullosa — NCT00825565.
• Registry record last updated 2018-02-28; status last verified 2018-01.
• Results first posted 2013-01-01.
• 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.

18. Record Summary

NCT00825565 is a completed Phase 2, open-label pilot study sponsored by Northwestern University. It enrolled eight subjects in a single Alwextin cream group, and the record states that all eight completed the study. The cream contained allantoin 3% and was applied topically to the entire body once daily. The study began in 2009-02, with primary completion in 2010-11.

The primary outcome was physician assessment of individual EB signs at baseline and 12 weeks, with ratings described across several signs and body areas. The primary outcome results, the other outcome results, and statistical analyses are not reported in the registry record. The endpoint analysis population is described by whole-body use for the entire month, but its size is not reported.

For safety, zero of eight participants at risk were listed as affected by serious adverse events, and four of eight were listed as affected by other adverse events. Deaths are not reported in the registry record. The single-group design does not provide a randomized comparison.