Study Testing Response Effect of KY1005 Against Moderate-to-Severe Atopic Dermatitis, The STREAM-AD Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Testing Response Effect of KY1005 Against Moderate-to-Severe Atopic Dermatitis, The STREAM-AD Study (NCT05131477), a randomized phase 2 study. The primary outcome is Percentage Change in EASI (Eczema Area and Severity Index) From Baseline to Week 16 (Part 1).

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase IIb dose-ranging study of KY1005 in adult participants with moderate-to-severe atopic dermatitis. The registry lists five Part 1 groups: four KY1005 regimens and placebo. The dose regimens were 250 mg with a 500 mg loading dose, 250 mg without a loading dose, 125 mg, and 62.5 mg; each listed regimen was administered every 4 weeks. The registry records quadruple masking as well as double blinding in the study title, but does not explain which people or roles were masked.

The registry lists enrollment as 390. The posted Part 1 primary-outcome group counts range from 77 to 79 participants per group; these are the group counts for that outcome and should not be interpreted as a total across all study parts or outcomes. The trial is marked completed. Its listed start date is 2021-12-13 and its primary completion date is 2023-04-26.

The brief summary describes a screening period of 28 days and study participation extending up to approximately day 477, including safety follow-up, unless participants entered a long-term extension protocol. Part 2 included participants re-randomized from Part 1 as well as a placebo group continuing from Part 1. Its results therefore address a different study period and population structure from the initial randomized Part 1 comparison. Details of the original sample-size justification, allocation procedures, and the reasons for particular Part 2 group sizes 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: The study was performed in 2 parts: Part 1 for all population (baseline to Week 24) for efficacy and safety and Part 2 for Part 1 Responders (Week 24 to Week 52 for efficacy and Week 24 to Week 68 for safety). Responders are defined as participants who achieved ≥EASI 75 and/or IGA 0/1 at Week 24.

Only the first 6 of 14 groups are shown.

PART 1

Reasons for not completing this period:

PART 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set for Part 1. The Full Analysis Set (FAS1) for Part 1 included all randomized participants up to week 24. Efficacy analyses were based on treatment allocated at randomization. The Primary efficacy endpoint is the percentage of change in EASI from Baseline to Day 113 (Week 16). The primary analysis was conducted on FAS1 after all the randomized patients had reached the Day 169 (Week 24) visit/ early termination. Missing data were imputed by multiple imputation.

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 Percentage Change in EASI (Eczema Area and Severity Index) From Baseline to Week 16 (Part 1), measured over Baseline to week 16.

The primary endpoint was percentage change in EASI from baseline to Week 16 in Part 1. EASI, the Eczema Area and Severity Index, is an investigator-assessed measure of atopic dermatitis extent and severity. Its scores range from 0 to 72, with higher scores indicating worse condition. Percentage change expresses how the score at the follow-up assessment compares with the baseline score; negative values in the posted results indicate reductions from baseline.

EASI is used as a structured clinical measure because it combines assessment of disease extent and severity into a single score. A percentage-change endpoint can describe change relative to participants’ baseline scores, while the group comparison assesses whether the average change differed between a KY1005 regimen and placebo. The reported group values are least-squares means with standard errors. The sponsor’s reported comparisons use ANCOVA and give least-squares mean differences, confidence intervals, and p-values.

The endpoint is a group-level measure at a specified follow-up time. It does not by itself describe every aspect of atopic dermatitis, a participant’s experience, or outcomes beyond the measured period. The registry record does not report the full statistical definition of percentage change or all details of how missing Week 16 measurements were handled.

7. Results Posted in the Registry

• 250 mg (500 mg LD) KY1005 (Part 1): mean -61.50 versus -29.40 on control; difference -32.10 (95% CI -45.18 to -19.02), standardized effect d = -0.77; z-test p = <0.001.
• 250 mg (no LD) KY1005 (Part 1): mean -56.80 versus -29.40 on control; difference -27.40 (95% CI -40.36 to -14.44), standardized effect d = -0.66; z-test p = <0.001.
• 125 mg KY1005 (Part 1): mean -51.60 versus -29.40 on control; difference -22.20 (95% CI -35.16 to -9.24), standardized effect d = -0.54; z-test p = <0.001.
• 62.5 mg KY1005 (Part 1): mean -59.60 versus -29.40 on control; difference -30.20 (95% CI -43.08 to -17.32), standardized effect d = -0.73; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage Change in EASI (Eczema Area and Severity Index) From Baseline to Week 24 (Part 1)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • 250 mg (500 mg LD) KY1005 (Part 1): mean -64.40 versus -27.60 on control; difference -36.80 (95% CI -51.30 to -22.30), standardized effect d = -0.80; z-test p = <0.001.
  • 250 mg (no LD) KY1005 (Part 1): mean -52.20 versus -27.60 on control; difference -24.60 (95% CI -39.06 to -10.14), standardized effect d = -0.53; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for 250 mg (500 mg LD) KY1005 (Part 1) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for 250 mg (no LD) KY1005 (Part 1) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Incidence Rate of Loss of EASI 50 (Part 2)

• Endpoint type: Event rate: events per unit of follow-up, compared as a rate ratio.
• Test: Poisson rate ratio, based on the estimated number of events and follow-up time.
• Result:
  • 250 mg KY1005 Re-randomized From the 250 mg (No LD) Arm (Part 2): 0.19 versus 0.27 (Events per patient-year) on control; rate ratio 0.69 (95% CI 0.08–5.91, approximate, Poisson model); p ≈ 0.736.
  • Placebo Re-randomized From the 250 mg (No LD) Arm (Part 2): 0.09 versus 0.27 (Events per patient-year) on control; rate ratio 0.33 (95% CI 0.04–2.57, approximate, Poisson model); p ≈ 0.288.
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between 250 mg KY1005 Re-randomized From the 250 mg (No LD) Arm (Part 2) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Placebo Re-randomized From the 250 mg (No LD) Arm (Part 2) and the control. The interval gives the range of effects that remain compatible with the data.

Incidence Rate of Loss of EASI 75 (Part 2)

• Endpoint type: Event rate: events per unit of follow-up, compared as a rate ratio.
• Test: Poisson rate ratio, based on the estimated number of events and follow-up time.
• Result:
  • 250 mg KY1005 Re-randomized From the 250 mg (No LD) Arm (Part 2): 0.38 versus 0.59 (Events per patient-year) on control; rate ratio 0.64 (95% CI 0.14–2.89, approximate, Poisson model); p ≈ 0.560.
  • Placebo Re-randomized From the 250 mg (No LD) Arm (Part 2): 0.49 versus 0.59 (Events per patient-year) on control; rate ratio 0.83 (95% CI 0.30–2.31, approximate, Poisson model); p ≈ 0.719.
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between 250 mg KY1005 Re-randomized From the 250 mg (No LD) Arm (Part 2) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Placebo Re-randomized From the 250 mg (No LD) Arm (Part 2) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the primary EASI assessment to Week 24 and include EASI response thresholds, investigator global assessment, and pruritus ratings. The registry also lists Part 2 outcomes related to loss of EASI response. Together, these measures address related but distinct aspects of disease severity and response: change in a continuous score, reaching specified response criteria, investigator assessment, symptom ratings, and maintenance or loss of response.

The posted Week 24 EASI group estimates generally show reductions from baseline in the active-treatment and placebo groups. Sponsor-reported ANCOVA comparisons are listed for two Week 24 dose groups; other Week 24 comparisons are not included in the reported analyses. The Part 2 loss-of-response rates and their recalculated comparisons concern a later period and a re-randomized population, so they do not serve as a direct extension of the initial Part 1 comparison. Full numerical results for all listed secondary outcomes are not reported in the registry record.

Secondary results can provide context for the primary endpoint, including whether patterns are similar across measures or follow-up times. They should not be treated as independent confirmation without considering how many outcomes and comparisons were examined. The record lists 55 outcome measures, 32 analyses, and 54 posted secondary outcomes. The multiplicity strategy and whether reported secondary p-values were adjusted are not reported in the registry record. When many comparisons are made, some apparently notable results can occur by chance; unadjusted secondary results therefore carry less evidential weight than a prespecified primary analysis interpreted within its statistical plan.

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

• Percentage Change in EASI (Eczema Area and Severity Index) From Baseline to Week 24 (Part 1)
• Percentage of Participants With at Least a 75% Reduction From Baseline in EASI (EASI 75) at Week 16 and Week 24 (Part 1)
• Percentage of Participants With a Response of IGA (Investigator Global Assessment) 0 or 1 and a Reduction From Baseline ≥ 2 Points (Part 1)
• Percentage of Participants With Improvement (Reduction) of Weekly Average of Pruritus NRS (Numerical Rating Scale) ≥ 4 With a Baseline Pruritus of ≥ 4 From Baseline (Part 1)
• Percentage of Participants With Improvement (Reduction) of Weekly Average of Pruritus NRS (Numerical Rating Scale) ≥ 4 With a Baseline Pruritus of ≥ 4 From Baseline (Part 2)
• Absolute Change From Baseline in EASI (Eczema Area and Severity Index) (Part 1)
• Percentage Change From Baseline in EASI (Eczema Area and Severity Index) (Part 1)
• Absolute Change From Baseline in EASI (Eczema Area and Severity Index) (Part 2)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it records percentage change in EASI rather than classifying participants into outcome categories. The posted group estimates are least-squares means, a model-based way of estimating group averages. Their accompanying standard errors describe uncertainty around those estimates. They are not standard deviations describing the spread of individual participant outcomes.

What does the sponsor’s ANCOVA comparison represent?

The sponsor reports ANCOVA comparisons of each KY1005 group with placebo. ANCOVA is a regression-based method for comparing outcomes between groups while accounting for specified covariates. The registry identifies ANCOVA as the method but does not report the full model specification, the covariates included, or how model assumptions were assessed. The resulting least-squares mean difference is an adjusted group contrast, not simply a subtraction of the two posted group means.

A confidence interval gives a range of values compatible with the data and the statistical model at a stated confidence level. It communicates uncertainty about the estimated group contrast; it is not a range containing a fixed proportion of individual participants’ responses. A p-value measures how incompatible the data are with a specified null hypothesis under the analysis assumptions. Neither a confidence interval nor a p-value alone describes clinical importance.

What are the recalculated comparisons?

The recalculated comparisons are simple, unadjusted comparisons using the posted group summary statistics. They estimate mean differences and provide approximate confidence intervals and p-values. The pooled standard deviations used in these calculations are approximate, because the calculations derive variability from the reported standard errors. These recalculations are useful as a transparent check on the summary data, but they do not reproduce the sponsor’s ANCOVA model or its adjustment. The registry does not flag a discrepancy between the posted summary statistics and the reported primary analyses.

For a continuous endpoint, a mean difference represents the contrast between group averages on the endpoint scale. Here, negative differences indicate a greater average reduction in EASI for the KY1005 group relative to placebo. The interpretation depends on the direction and definition of the endpoint; a negative value is not inherently favorable for every possible measure.

How should the Part 2 rate comparisons be read?

Part 2 includes posted incidence rates for loss of EASI 50 and loss of EASI 75, expressed as events per patient-year. The recalculated comparisons use rate ratios: a ratio of 1 would indicate equal event rates, while a ratio below or above 1 indicates a lower or higher rate in the compared group, respectively. These are unadjusted recalculations, not sponsor-reported analyses; no sponsor-reported analyses are listed for these outcomes.

The rate calculations use a Poisson approach. In general, a Poisson model is suited to counts of events over time when its assumptions are reasonable. Over-dispersion—greater variation in counts than the model allows—can make uncertainty estimates too small if not addressed. The registry record does not report a sponsor analysis or a check for over-dispersion for these Part 2 comparisons. Some listed group rates are zero, and the comparisons have wide confidence intervals; sparse event information limits precision. The event-rate estimates should therefore be read as descriptive and uncertain, not as definitive evidence of a difference.

The registry identifies the Full Analysis Set for Part 1 as the primary efficacy population and says efficacy analyses were based on treatment allocated at randomization. The complete definition and handling of exclusions, missing observations, and analysis assumptions are not reported in the registry record. Statistical methods help clarify what the posted estimates represent, but they do not remove uncertainty arising from the data or unreported analysis details.

11. Confidence Intervals and Precision

The sponsor’s primary ANCOVA comparisons report 95% confidence intervals for all four KY1005 regimens versus placebo. The intervals range from -43.9 to -20.3 for the 250 mg regimen with a 500 mg loading dose, -39.1 to -15.6 for 250 mg without a loading dose, -34.0 to -10.4 for 125 mg, and -41.9 to -18.5 for 62.5 mg. Each reported interval lies below zero, the value corresponding to no difference in the modeled group contrast. These intervals are conditional on the sponsor’s model and its assumptions.

The recalculated unadjusted intervals are not identical to the sponsor’s intervals. For example, the recalculated interval for the 250 mg regimen without a loading dose is -40.36 to -14.44, compared with the sponsor’s -39.1 to -15.6. That difference is consistent with the fact that the recalculation and ANCOVA use different methods. The registry record does not provide enough model detail to independently reproduce the adjusted estimates.

A narrower confidence interval indicates greater statistical precision about a group contrast, while a wider interval indicates more uncertainty. Precision is distinct from clinical importance: an interval can be estimated precisely without establishing how meaningful the difference is to patients. Confidence intervals also do not account for every possible source of uncertainty, including limitations in the study design, unreported model choices, or missing data.

For the Part 2 incidence-rate comparisons, the recalculated intervals are wide and include 1, the value representing equal rates. These analyses are based on small re-randomized groups, including groups with zero recorded event rates. The resulting uncertainty means that the rate estimates alone do not resolve whether the compared rates differ. No sponsor-reported confidence intervals or tests are listed for these rate outcomes.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on observed effects, not the original trial’s design assumptions. For the continuous outcomes, the figures are participants per arm. The Part 2 incidence-rate calculations also give participants per arm; the stated convention is that time-to-event calculations using the Schoenfeld method give total events, but these rate calculations are not presented as time-to-event calculations.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers detecting a stated fraction of the observed effect. The 80% power column gives the planned participants per arm for an illustrative design with an 80% chance of detecting that assumed effect under the calculation’s assumptions, if the effect and model assumptions are correct. The 90% column gives the corresponding planning count for a 90% chance. These are planning targets, not guarantees.

The rows that use 100%, 75%, and 50% of the observed effect illustrate how the required group size changes as the assumed effect changes. Smaller effects need more participants to detect with the same target power, all else equal. That pattern is reflected in the sample-size curve: a more modest assumed effect requires a larger planned sample.

These figures are not observed power. They are hypothetical planning calculations derived from the observed estimates, and the observed effect may not be the effect a future study would see. The original trial’s sample-size justification and design assumptions are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -32.100; pooled standard deviation σ = 41.700.
2. n = 2 × (1.96 + 0.842)² × 41.700² / -32.100² = 26.5, rounded up to 27 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 <- -32.1                      # observed difference in means
sigma <- 41.6999934597771                     # 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(5131477)
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 = 27 (80% power), 36 (90% power)
 75% of observed effect: n per arm = 48 (80% power), 64 (90% power)
 50% of observed effect: n per arm = 106 (80% power), 142 (90% power)
power.t.test: 27.5 
Simulated power at n = 27 per arm: 0.792 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s reported primary comparisons use ANCOVA and are the trial’s own analyses. They estimate adjusted least-squares mean differences, with reported 95% confidence intervals and p-values. For example, the sponsor reports a difference of -32.1 for the 250 mg regimen with a 500 mg loading dose and -27.3 for 250 mg without a loading dose. The sponsor’s reported analyses also include the 125 mg and 62.5 mg regimens.

The recalculated comparisons are separate, unadjusted calculations from the posted group summaries. They do not reproduce ANCOVA or use the sponsor’s full model. The recalculated estimate for 250 mg without a loading dose is -27.4, whereas the sponsor’s reported ANCOVA estimate is -27.3; other recalculated comparisons are also close to the reported estimates. Small differences can arise because the methods and information used differ.

The registry record does not identify a discrepancy between the posted data and the reported primary analyses. The sponsor’s ANCOVA results should therefore be treated as the primary reported trial analysis, while the recalculations serve as an approximate, unadjusted cross-check. The recalculations do not replace or revise the sponsor’s analysis. Sponsor-reported results are not listed for the Part 2 incidence-rate comparisons, so those comparisons should be understood only as exploratory recalculations from posted summaries.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a trial evaluates multiple doses, endpoints, time points, or statistical comparisons. As the number of tests grows, the chance of at least one apparently significant result can increase if each test is interpreted separately without adjustment. This study has four KY1005 dose comparisons with placebo for the primary endpoint and a broad set of secondary outcomes. The registry lists 55 outcome measures, 32 analyses, and 54 posted secondary outcomes.

The registry record does not report whether the primary comparisons were adjusted for multiplicity, whether a testing hierarchy or other control strategy was prespecified, or whether secondary p-values were adjusted. The sponsor labels the primary comparisons as superiority analyses, but that label alone does not establish how family-wise error or another multiplicity criterion was handled. The recalculated p-values are unadjusted and should not be treated as multiplicity-controlled evidence.

The primary efficacy population is described as the Full Analysis Set for Part 1, which included randomized participants up to week 24. The registry also states that efficacy analyses were based on treatment allocated at randomization. It does not fully report the population rules for every outcome, the handling of intercurrent events, or the missing-data method for the primary endpoint. The brief description of the primary endpoint is incomplete, and a complete statistical analysis plan is not reported in the registry record.

These omissions limit independent assessment of how planned decisions affected the estimates and tests. They do not by themselves invalidate the reported results, but they mean readers should distinguish the reported analysis from questions the registry record does not answer. In particular, the available record does not establish which outcomes or comparisons were designated in advance beyond the stated primary endpoint, or how analyses were selected for posting.

16. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ankle fracture (8.3%), umbilical hernia (7.7%), abnormal loss of weight (3.6%), rotator cuff syndrome (3.6%), spinal osteoarthritis (3.6%).

The registry reports serious adverse events and other adverse events separately by study group. In Part 1, serious adverse events were reported for 2 participants in the 250 mg group with a 500 mg loading dose, 0 in the 250 mg group without a loading dose, 1 in the 125 mg group, 5 in the 62.5 mg group, and 1 in the placebo group. The reported numbers at risk for these serious-event summaries were 77, 78, 77, 78, and 78, respectively.

The counts for other adverse events in those Part 1 groups were 42, 39, 39, 41, and 41, respectively. The registry also lists safety results for Part 2 groups that were re-randomized or continued from Part 1. Those groups have different sizes and histories, so their counts should be read within their own group definitions rather than directly combined with Part 1.

No deaths are reported in any of the listed groups. These counts describe events recorded in the registry; they do not establish causality or allow a complete comparison of risk. The registry record does not provide event-level timing, exposure-adjusted safety analyses, or additional context needed to interpret differences across groups. The serious-event figures should therefore be considered descriptive and read alongside the definitions and follow-up periods used for each group.

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

The posted primary results show that the mean EASI percentage change from baseline to Week 16 was more negative in each KY1005 group than in the placebo group. The sponsor’s reported ANCOVA comparisons also estimate negative differences versus placebo, and their reported 95% confidence intervals exclude zero. This describes the measured group averages and the statistical uncertainty under the reported model.

It does not mean that every participant had the same change, or that the group average predicts an individual outcome. It also does not establish that a particular dose is best: the study compared several regimens, and the posted estimates have uncertainty. Nor does the primary endpoint capture every symptom, experience, or aspect of atopic dermatitis. EASI is an investigator-assessed measure of extent and severity, and the primary result concerns a specified follow-up time in Part 1.

The Week 24 and Part 2 outcomes provide additional information but have different follow-up periods, endpoints, and, for Part 2, re-randomized groups. The Part 2 rate comparisons are unadjusted recalculations with wide intervals and no sponsor-reported analyses listed. Secondary results are also subject to uncertainty about multiplicity and analysis plans that are not described in the registry record.

The trial is marked completed, but the registry record alone does not answer every question about longer-term outcomes, missing data, generalizability, or the prespecified statistical plan. These findings are statistical summaries of a clinical trial, not medical advice and not a prediction for a particular person. Interpretation should remain limited to the populations, endpoints, comparisons, and follow-up described in the record.

18. Why This Trial Matters Statistically

This trial illustrates why a multi-arm randomized study needs to be read through both its group estimates and its comparative analyses. The primary endpoint reports change in a continuous EASI measure across four KY1005 regimens and placebo. The sponsor’s ANCOVA contrasts provide the principal adjusted comparisons, while unadjusted recalculations offer a limited cross-check based on summary statistics. Similar estimates do not make the analyses interchangeable.

It also highlights the distinction between statistical evidence and precision. Confidence intervals describe uncertainty around estimated group differences, while p-values address compatibility with a null hypothesis under a model. Neither alone conveys clinical importance, and neither accounts for questions left unanswered by an incomplete registry record. The availability of multiple dose comparisons and many secondary outcomes also makes multiplicity an important interpretive issue.

The Part 2 outcomes show a different statistical challenge. Event rates based on re-randomized groups can be imprecise, especially where event information is sparse. Rate ratios and their intervals need to be read together; an estimate alone can give a misleading impression of certainty. The absence of sponsor-reported analyses for those rate outcomes further limits the strength of any inference from the recalculations.

More broadly, the trial demonstrates the value of distinguishing primary from secondary outcomes, adjusted from unadjusted analyses, and observed estimates from planning illustrations. This separation helps readers judge what the registry results support without overstating their scope.

19. 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. The primary result concerns a single Week 16 EASI endpoint in Part 1. Although Week 24 EASI results are also posted, the registry does not report sponsor analyses for every dose comparison at that time point. The record lists many other outcome measures, but detailed results for all of them are not included in the available information.

The description of the primary analysis population identifies the Full Analysis Set for Part 1 and says treatment allocation at randomization was used for efficacy analyses. However, the full analysis plan, model covariates, missing-data methods, and handling of intercurrent events are not reported in the registry record. The primary endpoint description is incomplete, and the original sample-size justification is not reported. These gaps limit independent reproduction and assessment of analysis choices.

Part 2 differs from the initial randomized comparison because it includes re-randomized groups and a placebo group continued from Part 1. The posted rate comparisons use relatively small groups and include zero event rates; their confidence intervals are wide, and sponsor-reported analyses are not listed. Those results should not be treated as definitive comparative evidence.

The registry lists multicenter enrollment and completed status, but does not report enough information to assess representativeness, adherence, site-level variation, or the effects of treatment discontinuation. The reported outcomes also do not establish longer-term effects beyond the described follow-up or capture all dimensions of disease burden. These limitations narrow the conclusions that can be drawn from the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study Testing Response Effect of KY1005 Against Moderate-to-Severe Atopic Dermatitis, The STREAM-AD Study — NCT05131477.
• Registry record last updated 2025-07-03; status last verified 2025-06.
• Results first posted 2025-07-03.
• 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.

23. Record Summary

The registry describes a completed, randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase IIb dose-ranging study of KY1005 in adults with moderate-to-severe atopic dermatitis. Part 1 compared four KY1005 regimens with placebo. The primary endpoint was percentage change in EASI from baseline to Week 16.

The posted Part 1 group means show reductions in EASI in all groups, with more negative average percentage changes in the KY1005 groups than in placebo. Sponsor-reported ANCOVA comparisons estimate differences versus placebo, with 95% confidence intervals and p-values. Unadjusted recalculations are close but are not the sponsor’s model-based analyses.

Secondary outcomes include Week 24 EASI, response thresholds, investigator assessment, pruritus, and Part 2 loss-of-response rates. Multiplicity procedures, missing-data methods, and the original sample-size justification are not reported in the registry record. Part 2 rate comparisons are unadjusted recalculations with substantial uncertainty.