This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Participants With Ichthyosis (NCT04697056), a randomized phase 2 study. The primary outcome is Change From Baseline in Ichthyosis Area Severity Index (IASI) Total Score at Week 16.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04697056 |
| Phase | Phase 2 |
| Condition | Ichthyosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Vanda Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled participants with ichthyosis. The registry record lists an enrollment of 5. Further details about participant characteristics, such as age, disease subtype, or baseline severity, are not reported in the registry record.
Intervention
Participants assigned to imsidolimab received a starting dose of 400 milligrams on Day 1, followed by 200 mg every 4 weeks on Days 29, 57 and 85, by subcutaneous injection.
Comparator
The comparator was matching placebo, administered on Day 1 and then every 4 weeks on Days 29, 57 and 85, by subcutaneous injection. The study was randomized and placebo-controlled.
Primary question
The planned primary question concerned change from baseline in the Ichthyosis Area Severity Index (IASI) total score at Week 16. The registry record says the study ended before that primary time point, so efficacy data were not collected and were not analyzed. Consequently, the posted results do not estimate whether IASI scores changed differently between the imsidolimab and placebo groups.
The clinical question is therefore best understood as the question the trial was designed to address, not as a question answered by its posted efficacy results. The planned comparison would have examined disease severity over time in the treatment and placebo groups. Since the required endpoint data are absent, no treatment-effect estimate or uncertainty interval for that comparison is available in the registry record.
3. Trial Design
The registry describes a Phase 2, randomized, double-blind, placebo-controlled study with a parallel-group model and quadruple masking. The condition listed is ichthyosis, and the interventions are imsidolimab and placebo. The record identifies Vanda Pharmaceuticals as sponsor. It lists the study start as 2021-01-25, primary completion as 2021-11-19, and status as terminated. The reason for termination is not reported in the registry record.
In a parallel-group design, participants are assigned to a treatment group and followed within that group rather than crossing between treatments. Random allocation is intended, in general, to reduce systematic differences between groups at the point of assignment. The registry identifies the study as randomized but does not report the allocation ratio or the method used to generate or conceal the allocation sequence.
The record labels masking as quadruple and the study as double-blind. Which specific roles were masked is not reported in the registry record. The active and placebo regimens followed the same injection schedule: treatment on Day 1 and subsequent doses every 4 weeks on Days 29, 57 and 85. The imsidolimab regimen included a starting dose of 400 milligrams and subsequent doses of 200 mg; the placebo was described as matching placebo.
Enrollment was 5. The primary endpoint was planned for Week 16, but the study was terminated before that time point. The registry explicitly states that efficacy data were not collected and therefore were not analyzed. The record lists eight outcome measures and zero analyses. It does not report a statistical analysis plan, a sample-size justification, or the reason the study ended early.
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: 7 participants were screened for eligibility and 5 participants were randomized into the study.
Overall Study
| Stage | Imsidolimab | Placebo |
|---|---|---|
| STARTED | 4 | 1 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 4 | 1 |
Reasons for not completing this period:
| Reason | Imsidolimab | Placebo |
|---|---|---|
| Termination of the participant participation by the Investigator or Sponsor | 4 | 1 |
Analysis population for the primary outcome, as defined in the registry: Due to early study termination before the primary time point, efficacy data was not collected, therefore, not analyzed.
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: Intent-to-Treat (ITT) analysis set included all randomized participants.
| Characteristic | Unit | Imsidolimab | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 1 | 5 | |
| Age, Continuous | years | 39.0 (SD 20.15) | 66.0 | 44.4 (SD 21.22) |
| Sex: Female, Male: Female | Participants | 3 | 0 | 3 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 | 1 | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Ichthyosis Area Severity Index (IASI) Total Score at Week 16, measured over Baseline and Week 16.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The planned primary endpoint was change from baseline in the Ichthyosis Area Severity Index (IASI) total score at Week 16. The registry describes IASI as a measure of ichthyosis severity that combines erythema and scaling severity with the percentage of body surface area affected across the head and neck, upper limbs, trunk, and lower limbs. Each region contributes according to its body-surface-area weighting.
The IASI-Erythema and IASI-Scaling component scores each range from 0 to 24. The total score is their sum and ranges from 0 to 48; higher scores indicate a worse disease state. A change-from-baseline endpoint is generally used to describe how a participant's measured score differs from the starting measurement by a specified follow-up time. Comparing those changes between randomized groups can address whether the groups followed different score trajectories, subject to the analysis methods and available data.
In this study, the endpoint was not observed in the posted efficacy results. The registry states that termination occurred before the primary time point, so efficacy data were not collected and were not analyzed. There is consequently no reported baseline-to-Week-16 change, group contrast, or estimate of the precision of that contrast. The scale's definition explains what the planned measurement would represent; it does not supply evidence about participants' scores or changes in this trial.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the planned primary efficacy outcome is unavailable. Although the registry identifies change in IASI total score at Week 16 as the primary endpoint, it states that the study was terminated before the primary time point and that efficacy data were not collected or analyzed. Thus, the posted results do not provide an estimate of the difference between imsidolimab and placebo for the primary question.
Enrollment was 5. This is a small amount of trial information for estimating a treatment effect, but the more immediate limitation is that the primary efficacy measurements were not collected. There is no posted group mean change, difference in change, confidence interval, or p value for the primary endpoint. The registry record lists zero analyses. Without an efficacy estimate, the direction and magnitude of any between-group difference cannot be assessed, and its precision cannot be described.
The record does include adverse-event summaries. For serious adverse events, the imsidolimab group lists 4 at risk and 0 affected; the placebo group lists 1 at risk and 0 affected. For other adverse events, the imsidolimab group lists 4 at risk and 1 affected, while the placebo group lists 1 at risk and 1 affected. These are descriptive counts in a very small trial, not a basis for a stable comparison of event rates. The registry reports 0 deaths in each group. No serious adverse-event terms are listed.
Statistical interpretation must keep the planned question separate from the results that were actually recorded. Randomization describes how treatment assignment was intended to occur; it does not compensate for absent outcome measurements. Similarly, the existence of a defined severity scale does not mean that scores were collected. The record supports a description of the design and the available safety counts, but not a conclusion about the primary efficacy contrast.
The registry status is terminated, but the reason for termination is not reported in the registry record. The record also does not explain whether there were operational, recruitment, safety, or other considerations behind that status. Without such information, the cause of early termination should not be inferred. The posted data are therefore most informative as a record of an interrupted study with incomplete efficacy evidence, rather than as an estimate of treatment efficacy.
9. Statistical Methods Explained
The statistical methods that can be interpreted are limited by the absence of efficacy data and analyses. The registry specifies a randomized, parallel-group, placebo-controlled Phase 2 design and names change from baseline in IASI total score at Week 16 as the primary endpoint. It does not report the statistical analysis plan, the method for comparing groups, or the handling of missing endpoint measurements. Those details are not reported in the registry record, so a particular model or test should not be attributed to this trial.
What randomization contributes
In general, randomization assigns participants to groups by a chance-based procedure. Its purpose is to make systematic differences between groups less likely at the start of a study, including differences that researchers may not have measured. It does not guarantee that groups will be similar in every respect, especially in a small study. Here, the registry says the study was randomized, but the allocation method and ratio are not reported in the registry record. Randomization also cannot create outcome information when the endpoint was not collected.
What masking contributes
The record identifies the study as double-blind and lists quadruple masking. In general, masking can reduce the influence of treatment knowledge on participant reporting, clinical assessments, and study conduct. The record does not identify which people or roles were masked, or describe procedures for maintaining masking. Since the primary efficacy outcome was not collected, masking cannot resolve the absence of that outcome or enable an efficacy comparison.
What a change score would describe
In general, a change score represents a follow-up measurement relative to a baseline measurement. For this trial, the planned score was the IASI total score at baseline and Week 16. The scale combines erythema and scaling across body regions, accounting for the percentage of body surface area affected and the stated regional weights. Higher total scores indicate worse disease state. A group comparison of changes could summarize whether the measured scores changed differently in the randomized groups, but the record contains no such change estimates.
A statistical estimate is usually accompanied by an uncertainty measure, such as a confidence interval. In general, a confidence interval communicates a range of effect values compatible with the data and the method used, under its assumptions. It is not a substitute for the effect estimate, and its interpretation depends on the analysis. No primary effect estimate or confidence interval is reported in the registry record because efficacy data were not collected and analyzed.
Why small samples limit precision
In general, estimates based on few observations tend to be sensitive to the information from each participant and may have substantial uncertainty. Small samples also make it difficult to assess whether randomized groups happen to differ at baseline. Enrollment was 5, and the available safety summaries list 4 at risk in the imsidolimab group and 1 at risk in the placebo group. These counts are descriptive; no new group totals or comparative rates can be inferred from them. Most importantly, sample size alone does not yield an efficacy estimate when the relevant outcome measurements are absent.
Multiplicity and secondary outcomes
The registry lists secondary outcomes involving percent change in IASI total score, IASI50, changes and percent changes in IASI-E and IASI-S scores, and treatment-emergent adverse events. Multiple outcomes can raise a multiplicity concern when several hypotheses are tested, because the chance of at least one apparently notable result can increase across a set of tests. In general, researchers may prespecify a hierarchy or adjustment approach to address that issue. The registry record does not report such an approach, and it lists zero analyses. The absence of analyses means there are no posted secondary efficacy comparisons to interpret.
What is not established
The registry does not report an analysis population, a missing-data strategy, an imputation method, or a model for the primary endpoint. It also does not report interim analyses or a sample-size justification. Those omissions do not establish that no such procedures existed outside the registry; they mean that they are not reported in the registry record. Because the planned efficacy data were not collected, the record cannot show whether any chosen analysis assumptions would have been reasonable or how the treatment comparison would have been estimated.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the IASI total-score endpoint as primary and several secondary outcomes related to IASI total score, IASI50, IASI-E, IASI-S, and treatment-emergent adverse events. When a trial assesses multiple outcomes or multiple hypotheses, multiplicity can affect the interpretation of statistical tests: considering many tests can increase the chance that at least one result appears notable by chance. General approaches include prespecifying an order of testing or adjusting inference across outcomes. Whether either approach was planned for this study is not reported in the registry record.
The record lists eight outcome measures and zero analyses. The early termination occurred before the primary time point, and efficacy data were not collected or analyzed. As a result, the posted results do not permit an assessment of multiplicity-adjusted or unadjusted efficacy findings. No efficacy p values or treatment-effect estimates are reported.
Missing-data methods and analysis populations are also not reported in the registry record. The record does not identify an intention-to-treat, per-protocol, or other efficacy population, nor does it describe imputation, exclusion rules, or sensitivity analyses. Since the primary efficacy data were not collected, this is more fundamental than ordinary missing follow-up measurements: the registry does not provide the endpoint observations needed for the planned comparison. The reasons for termination and the extent of any other data collection are not reported in the registry record. Therefore, no assumptions about the missing outcomes or participant-level analysis should be made.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Imsidolimab | 0 | 4 | 0.0% |
| Placebo | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Imsidolimab | 0 of 4 |
| Placebo | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Imsidolimab | 1 of 4 |
| Placebo | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Imsidolimab | Placebo |
|---|---|---|---|
| Fatigue | General disorders | 1 of 4 | 0 of 1 |
| Peripheral swelling | General disorders | 0 of 4 | 1 of 1 |
| Herpes simplex reactivation | Infections and infestations | 1 of 4 | 0 of 1 |
| Procedural pain | Injury, poisoning and procedural complications | 0 of 4 | 1 of 1 |
| Inguinal mass | Musculoskeletal and connective tissue disorders | 0 of 4 | 1 of 1 |
| Headache | Nervous system disorders | 1 of 4 | 0 of 1 |
| Night sweats | Skin and subcutaneous tissue disorders | 0 of 4 | 1 of 1 |
| Skin lesion | Skin and subcutaneous tissue disorders | 0 of 4 | 1 of 1 |
The registry reports serious adverse-event counts separately from other adverse-event counts. In the imsidolimab group, 4 participants were at risk for serious adverse events and 0 were affected; 4 were at risk for other adverse events and 1 was affected. In the placebo group, 1 participant was at risk for serious adverse events and 0 were affected; 1 was at risk for other adverse events and 1 was affected. Deaths are listed as 0 in each group. No serious adverse-event terms are listed.
These are counts, not comparative rates or adjusted estimates. With enrollment of 5 and the group-specific at-risk counts shown, each event count represents very limited information. In general, a count of zero in a small group does not establish that an event is impossible or that risks are equivalent between groups. Likewise, the other-event counts do not establish a treatment-related difference. The registry record does not provide event descriptions for the other adverse events or further detail on seriousness assessment, timing, or attribution. The figures should therefore be read as a limited descriptive safety summary, not as a precise comparison or a complete account of safety.
12. What the Result Does, and Does Not, Mean
The posted results establish that this was a randomized, placebo-controlled Phase 2 study of imsidolimab for ichthyosis and that it was terminated before the planned primary time point. The record gives an enrollment of 5 and describes the intended Week 16 IASI total-score endpoint. It also gives limited adverse-event counts by group. These registry entries describe the trial and its available results, but they do not answer the planned efficacy question.
There is no reported Week 16 IASI change, treatment-versus-placebo estimate, confidence interval, or p value. The record explicitly says that efficacy data were not collected and therefore were not analyzed. It would be inaccurate to interpret the absence of an efficacy result as evidence of no effect, evidence of benefit, or evidence of equivalence. None of those conclusions follows from an outcome that was not measured and analyzed.
The adverse-event counts are also not a reliable basis for broad comparisons. They are descriptive observations from small groups, without reported comparative analysis or detailed event terms for the other adverse events. The absence of serious events in the listed counts does not prove that serious events cannot occur, and the reported other-event counts do not establish causation. The data should not be extended beyond the participants and observations recorded.
The trial's termination is an important part of interpreting the record, but its reason is not reported in the registry record. No explanation should be inferred from termination alone. Nor does the record report the analysis populations, missing-data procedures, sample-size justification, or full statistical plan. The defensible conclusion is narrow: the design and planned primary endpoint are documented, while the efficacy comparison is unavailable and the safety summary is limited. Further conclusions about treatment effect or the circumstances of study termination are not supported by the posted results.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a planned endpoint and an observed result. A clearly defined endpoint can show what investigators intended to measure, but it cannot answer the clinical question unless the measurements are collected and analyzed. Here, the registry identifies a clinically interpretable severity score and a planned Week 16 comparison, yet explicitly states that efficacy data were not collected because the study ended before that time point.
The record also shows why a randomized design does not, by itself, guarantee an informative treatment-effect estimate. Randomization is a tool for reducing systematic differences between groups; it does not overcome early termination or replace missing outcome data. With enrollment of 5, the study's available safety counts are limited descriptive information. They cannot provide a precise comparison of adverse-event risks, and the absent efficacy data cannot support a comparison of changes in disease severity.
For readers assessing clinical evidence, the case reinforces the importance of distinguishing no reported result from a reported null result. A null result would require measured data and an analysis that estimates an effect, with uncertainty. In this record, the primary efficacy outcome is not analyzed at all. There is no basis to infer that the groups had the same outcome, or that either group had a particular change.
The record also highlights the value of transparent reporting about study status and missing analyses. The study is listed as terminated, while the reason for termination and the statistical analysis plan are not reported in the registry record. Those gaps limit what can be learned about both the study's conduct and its intended inferential approach. The most useful statistical reading is therefore one that preserves the boundary between design information, observed safety counts, and an efficacy result that is not available.
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 principal limitation is the absence of the primary efficacy data. The registry states that the study was terminated before the primary time point and that efficacy data were not collected or analyzed. As a result, the planned change-from-baseline comparison in IASI total score at Week 16 cannot be estimated from the posted results.
Enrollment was 5, and the safety summaries list 4 at risk in the imsidolimab group and 1 in the placebo group. Such limited counts provide little information for comparing uncommon events or estimating event frequencies precisely. The record lists 0 serious adverse events in each group and 0 deaths in each group, but these observations do not establish absence of risk. The other adverse-event counts are not accompanied by detailed terms in the registry record.
The reason for termination is not reported in the registry record. The allocation ratio, allocation procedure, specific roles covered by masking, participant characteristics, and baseline IASI scores are also not reported. The registry does not describe the statistical analysis plan, analysis populations, missing-data handling, sample-size justification, or interim analyses. The record lists eight outcome measures but zero analyses.
These limitations constrain both efficacy interpretation and assessment of how the study was conducted. They should not be filled by assumptions about protocol decisions or unreported data. The posted information supports a description of the planned design and the limited safety counts, but it does not support an efficacy conclusion or a detailed reconstruction of the study's statistical methods.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Participants With Ichthyosis — NCT04697056.
- Registry record last updated 2025-09-16; status last verified 2022-11.
- Results first posted 2023-03-02.
- 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.
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18. Record Summary
NCT04697056 is a randomized, double-blind, placebo-controlled Phase 2 parallel-group study of imsidolimab in participants with ichthyosis, sponsored by Vanda Pharmaceuticals. The registry lists enrollment of 5, a start date of 2021-01-25, primary completion of 2021-11-19, and a terminated status.
The planned primary endpoint was change from baseline in IASI total score at Week 16. The registry states that the study ended before the primary time point, so efficacy data were not collected or analyzed. The record lists eight outcome measures and zero analyses. Serious adverse-event counts were 0 in each group; other adverse events affected 1 participant in each group, with group-specific at-risk counts of 4 for imsidolimab and 1 for placebo. The reason for termination and the statistical analysis plan are not reported in the registry record.