Efficacy and Safety of 100IR, 300IR, 500IR Sublingual House Dust Mite Tablets in Allergic Rhinitis Environment Exposure Chamber Model: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of 100IR, 300IR, 500IR Sublingual House Dust Mite Tablets in Allergic Rhinitis Environment Exposure Chamber Model (NCT01527188), a randomized phase 2 study. The primary outcome is Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 4 Hours (0-4h) of the Allergen Challenge.

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, parallel-group Phase II study. Its stated purpose was to assess three doses of sublingual house dust mite allergen tablets against placebo using an environmental exposure chamber model. The registry record identifies allergic rhinitis due to house dust mite as the condition under study and reports enrollment of 355 participants. The study status is completed.

The treatment groups received 100 IR, 300 IR, or 500 IR tablets, or a placebo tablet. The primary endpoint compared change from baseline to the end-of-treatment period, specified as 6 months. Baseline was the first allergen challenge before treatment initiation. The challenge took place in an Environmental Exposure Chamber, where participants’ nasal symptoms were scored during exposure.

The primary efficacy population is described as the Full Analysis Set: patients who received at least one dose of investigational product. The endpoint description further identifies the outcome population as patients at Visit 7 for whom data were available. The registry record does not report the original sample-size justification, the intended allocation ratio, details of the randomization procedure, or additional masking procedures. The term quadruple-masked is reported, but the identities of the masked parties are not reported in the registry record.

The primary endpoint was the area under the curve of the Rhinitis Total Symptom Score over the 4-hour challenge. A secondary outcome used the same score over the later 2-hour period of the challenge. The registry record lists one secondary outcome. It does not report the planned strategy for handling multiple dose comparisons or multiple outcomes.

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: Full Analysis Set (FAS): all patients who received at least one dose of the investigational product. (Number of patients at Visit 7 for whom data is available).

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: The Full Analysis Set included all randomized patients who received at least one dose of Investigational Product.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 4 Hours (0-4h) of the Allergen Challenge, measured over 6 months.

The primary endpoint was change from baseline to the end-of-treatment period in the area under the curve of the Rhinitis Total Symptom Score during the 4-hour allergen challenge. The timeframe was 6 months, and the outcome is expressed in RTSS * hour. The score sums four nasal symptoms: rhinorrhoea, nasal congestion, nasal pruritus, and sneezing. Each symptom is rated on a 0-3 scale.

During each challenge, the score was assessed every 15 minutes in the first 2 hours and every 30 minutes in the last two hours, yielding 13 timepoints from T0 to T240. The scores were plotted against time to calculate the area under the curve. This combines symptom intensity and its pattern across the challenge period into a single continuous measure, rather than treating one assessment time as the entire outcome.

A decrease in the area-under-the-curve value represents relief from house dust mite allergic symptoms according to the endpoint description. Thus, a more negative change from baseline indicates a larger reduction in the measured area under the curve. The chamber challenge provides a standardized exposure setting for comparing symptom-score changes, but the endpoint describes symptoms recorded during that challenge; it is not itself a measure of symptoms across ordinary daily life.

7. Results Posted in the Registry

• 100 IR: mean -715.83 versus -597.40 on control; difference -118.43 (95% CI -305.06 to 68.20), standardized effect d = -0.20; z-test p = 0.214.
• 300 IR: mean -769.21 versus -597.40 on control; difference -171.81 (95% CI -363.20 to 19.58), standardized effect d = -0.29; z-test p = 0.079.
• 500 IR: mean -795.58 versus -597.40 on control; difference -198.18 (95% CI -388.47 to -7.89), standardized effect d = -0.34; z-test p = 0.041.

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.

Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 2 Hours (2-4h) of the Allergen Challenge

• 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:
  • 100 IR: mean -390.34 versus -299.16 on control; difference -91.18 (95% CI -203.14 to 20.78), standardized effect d = -0.26; z-test p = 0.110.
  • 300 IR: mean -421.39 versus -299.16 on control; difference -122.23 (95% CI -237.06 to -7.40), standardized effect d = -0.35; z-test p = 0.037.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 100 IR and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for 300 IR than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry record lists one secondary outcome: change from baseline in the area under the curve of the Rhinitis Total Symptom Score during the later 2-hour period of the allergen challenge. It reports arm-level results for the three tablet doses and placebo, along with dose comparisons in the posted secondary analyses. Across the dose groups, the estimated changes are more negative than the placebo estimate, so the broad direction is consistent with the primary endpoint’s pattern.

The secondary outcome is related to the primary endpoint because it uses the same symptom score and challenge, but focuses on a different part of the challenge period. It therefore provides related, not independent, evidence. Agreement in direction can be informative, but it does not remove uncertainty in either endpoint or establish that the results generalize beyond the chamber setting.

Secondary results generally carry less weight when they are not protected by a prespecified multiplicity plan, because examining multiple outcomes and comparisons can increase the chance of a seemingly notable finding. The registry record does not report a multiplicity strategy or identify a hierarchy for interpreting primary and secondary outcomes. The recalculated secondary comparisons are unadjusted, and the sponsor’s own reported secondary analyses do not include every dose comparison. These limitations mean the secondary pattern should be treated as supportive context rather than as a separate confirmatory conclusion.

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

• Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 2 Hours (2-4h) of the Allergen Challenge

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference represent?

The endpoint is continuous, so the arm-level result is reported as a least-squares mean change with a standard error. The mean difference compares an active-dose group with placebo. A negative difference indicates a more negative average change in the active-dose group, consistent with a greater decrease in the symptom-score area under the curve. The units remain RTSS * hour. The interpretation is specific to the endpoint, time window, and challenge setting used in this study.

A difference is an estimate, not a certainty. It summarizes the contrast between groups in the analyzed data, while its uncertainty depends on the amount and variability of the data and on the analysis method. The trial’s posted sponsor analyses are ANCOVA estimates of differences in least-squares means. ANCOVA is a regression-based method that can compare groups while accounting for covariates included in the model. The registry record does not report which covariates were included, how they were selected, or the model details. Those particulars should not be inferred from the label ANCOVA alone.

What does the confidence interval communicate?

A confidence interval gives a range of values compatible with the observed estimate under the statistical model and its assumptions. A narrower interval indicates greater precision; a wider interval indicates less precision. It is not a range containing every participant’s response, nor does it represent the probability that the true effect lies within the particular interval. Intervals that include zero indicate that the data are compatible with no difference as well as with differences in either direction, at the interval’s stated confidence level.

The registry reports 95% confidence intervals for the sponsor’s ANCOVA contrasts. The simple recalculations use posted group means and standard errors to form unadjusted comparisons. They are not substitutes for the sponsor’s model-based analysis. Because the registry record indicates a discrepancy, the sponsor’s own reported analysis takes precedence.

Why can the simple recalculation differ?

The posted group summaries are least-squares means and standard errors. The recalculation derives an approximate pooled standard deviation from those standard errors and sample sizes, then uses it for an unadjusted comparison. This is an approximation, as indicated in the recalculation details. It does not reproduce an ANCOVA model or account for any covariate adjustment that may have been used in the sponsor analysis. The registry record does not provide enough model detail to identify the exact source of each difference.

Consequently, the recalculated comparisons and p-values are useful as a transparent check based on posted summary statistics, but should be read as approximate, unadjusted results. When the recalculated estimate or interval differs from the sponsor’s reported value, use the sponsor’s analysis as the primary reported result rather than treating the two approaches as interchangeable.

Why do variability and dispersion matter?

A group mean describes the center of the outcome distribution, while a measure of variability describes how spread out the individual outcomes are. Greater variability makes group differences harder to estimate precisely for a given amount of data. For continuous outcomes, standard errors quantify the uncertainty of estimated means; they are not the same as the spread of individual observations. The registry reports standard errors for the arm-level least-squares means, and the recalculation uses an approximate standard deviation derived from those summaries.

The approximation matters because the summary statistics do not reveal the full distribution of individual outcomes or the covariance structure used in an adjusted analysis. If data are strongly skewed, contain influential observations, or violate model assumptions, a mean-based analysis may not capture all relevant features. The registry record does not report diagnostic checks or distributional details, so their adequacy cannot be assessed from the posted summaries alone.

What do the p-values answer?

A p-value measures how unusual results at least as extreme as the observed data would be under a specified null hypothesis and model. It is not the probability that the null hypothesis is true, nor a measure of the size or importance of a difference. The recalculated p-values are explicitly unadjusted. The sponsor reports p-values for the 500 IR and 300 IR comparisons, but not for the 100 IR comparison. The record does not report whether p-values were adjusted for the several dose-versus-placebo comparisons or for the secondary outcome.

Because several comparisons appear in the results, an isolated p-value should not be interpreted without regard to the analysis plan and multiplicity. The registry record does not report an approach to multiplicity, so the statistical interpretation should emphasize estimates and confidence intervals alongside the p-values, and avoid treating an unadjusted threshold as the complete basis for a conclusion.

11. Confidence Intervals and Precision

The sponsor’s ANCOVA estimate for the 500 IR comparison is -198.18, with a 95% confidence interval from -389.82 to -6.55. This interval lies on the negative side of zero, but its width shows that the magnitude of the difference remains uncertain. The sponsor’s 300 IR interval extends from -363.87 to 20.24, and the 100 IR interval extends from -305.90 to 69.04. Both include zero and also allow for a range of negative differences.

The recalculated intervals are similarly broad: -305.1 to 68.2 for 100 IR, -363.2 to 19.58 for 300 IR, and -388.5 to -7.895 for 500 IR. These are approximate, unadjusted intervals based on posted summary statistics, rather than replacements for the sponsor’s ANCOVA intervals. The intervals are useful for seeing how much uncertainty surrounds each estimate; they should not be reduced to a yes-or-no interpretation of whether an interval crosses zero.

Precision is limited by the uncertainty reflected in the intervals and by what is not reported. The registry record does not provide participant-level data, model diagnostics, the covariates in the ANCOVA, or details about missing-data handling. The available estimates therefore do not allow an independent assessment of those features. A statistically compatible range can include differences with quite different magnitudes, so the point estimate alone should not be treated as a precise measure of the underlying contrast.

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 table and curve are planning illustrations based on the observed effect, not a reconstruction of the trial’s original design. For these continuous outcomes, the figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the planned participants per arm under those assumptions for an analysis with an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column describes the corresponding planning target with a 90% chance under the same assumptions. Power is a property of a planned design under assumptions, not the probability that a particular trial result is correct or that an effect exists.

Rows planning for 100% of the observed effect use the observed estimate as the target; rows for 75% or 50% use smaller targets. Smaller effects need more participants per arm to detect under the same assumptions. The displayed figures vary by comparison because the observed estimates and variability differ. They should be read as sensitivity illustrations: if a smaller effect is considered plausible, the planning requirement increases. This is not observed power.

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 = -118.430; pooled standard deviation σ = 583.104.
2. n = 2 × (1.96 + 0.842)² × 583.104² / -118.430² = 380.5, rounded up to 381 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 <- -118.43                      # observed difference in means
sigma <- 583.103879746139                     # 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(1527188)
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 = 381 (80% power), 510 (90% power)
 75% of observed effect: n per arm = 677 (80% power), 906 (90% power)
 50% of observed effect: n per arm = 1,523 (80% power), 2,038 (90% power)
power.t.test: 381.5 
Simulated power at n = 381 per arm: 0.798 (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 analyses use ANCOVA and give differences in least-squares means with 95% confidence intervals. For 500 IR, the sponsor reports -198.18, with an interval from -389.82 to -6.55 and p = 0.043. For 300 IR, the reported estimate is -171.82, with an interval from -363.87 to 20.24 and p = 0.079. For 100 IR, the estimate is -118.43, with an interval from -305.90 to 69.04; a p-value is not reported.

The recalculated comparisons use unadjusted calculations from the posted group means and standard errors, including an approximate pooled standard deviation. The resulting values are close to, but not identical to, some sponsor estimates and intervals. This is expected to be possible when a summary-statistic calculation does not reproduce the sponsor’s ANCOVA model. The registry record does not report enough model detail to explain the exact differences.

Because the record indicates a discrepancy, the sponsor’s own analysis takes precedence. The recalculations are best understood as a check based on the posted summaries, not as a correction of the sponsor’s analysis. The sponsor does not report a p-value for the 100 IR primary comparison, so the recalculated p-value should not be presented as though it were the sponsor’s result.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint involves comparisons of three tablet doses with placebo, and the registry record also lists a secondary endpoint. Testing several comparisons can increase the chance of finding at least one apparently notable result by chance if no adjustment or prespecified testing sequence is used. The registry record does not report whether the analysis controlled this multiplicity, whether any comparisons were designated as primary among the dose groups, or whether a hierarchical testing procedure was planned. The reported recalculated p-values are unadjusted.

The registry describes the primary population as the Full Analysis Set, consisting of patients who received at least one dose of investigational product. It also says the endpoint population includes patients at Visit 7 for whom data are available. This identifies the stated analysis population, but it does not explain how missing Visit 7 outcomes were handled, whether other visits were used, or how the analysis treated participants with incomplete outcome data. Those details are not reported in the registry record.

The record does not report the trial’s original sample-size justification, its detailed statistical analysis plan, interim analyses, model covariates, or the assumptions used for its own design. The planning illustration is based on the observed effect and should not be mistaken for the original trial calculation. These reporting gaps limit assessment of whether the posted analyses follow prespecified procedures and how robust the findings are to alternative missing-data or multiplicity approaches. They do not establish that a particular procedure was or was not used; the relevant information is simply not reported in the registry record.

16. 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: schizoaffective disorder (1.2%), nephrolithiasis (1.1%), meningitis (1.1%), convulsion (1.1%).

The registry reports serious adverse events in the safety groups as affected participants and participants at risk. In the 100 IR group, 1 of 89 participants was reported as affected; in the 300 IR group, 1 of 86 was affected; in the 500 IR group, 2 of 93 were affected; and in the placebo group, 0 of 87 were affected. These are counts of participants with serious adverse events, not counts of all event episodes.

The listed serious-event terms include schizoaffective disorder at 1.2%, nephrolithiasis at 1.1%, meningitis at 1.1%, and convulsion at 1.1%. The registry record does not report deaths in the posted safety information. These summaries do not establish whether an event was caused by treatment, and the small counts do not support precise comparisons of risk between groups. They should be read as descriptive safety information from the registry record, not as a complete account of all possible harms.

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

The posted results describe changes in a symptom-score measure during an allergen chamber challenge after 6 months. The sponsor’s primary analysis estimates are more negative for each tablet dose than for placebo. The 500 IR sponsor interval is entirely below zero, while the intervals for 100 IR and 300 IR include zero. This is a description of the estimated group contrasts and their reported uncertainty; it is not by itself a complete assessment of clinical importance.

The score combines four nasal symptoms over the challenge period, and the area under the curve captures their pattern across that period. A decrease is described in the registry as relief from house dust mite allergic symptoms. However, the registry record does not report a threshold for a clinically important difference. Statistical evidence and clinical importance are distinct questions: an estimate may be statistically compatible with a difference without showing whether that difference is meaningful to patients.

The study’s chamber model measures responses under a controlled allergen challenge. The results do not directly describe symptoms across everyday settings, long-term outcomes, or effects beyond the 6-month treatment period. The registry record also does not report enough detail about multiplicity, missing data, and model specification to fully evaluate the analysis plan. The results therefore should be interpreted within the specific population, endpoint, time frame, and setting reported, without extending them to claims not assessed by this trial.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares several doses with placebo using a continuous symptom outcome and reports both arm-level estimates and model-based contrasts. The dose-ranging structure allows readers to inspect whether the estimated contrasts vary across dose groups, while the confidence intervals show that the estimates remain uncertain. Looking at estimates and precision together is more informative than relying on a single p-value.

The trial also illustrates why a registry’s analysis details matter. A simple recalculation from group summaries can approximate an unadjusted comparison, but it may not reproduce an ANCOVA analysis. The sponsor’s model-based results are the primary reported analyses, and the recalculation is a distinct supplementary check. Clear distinctions between these approaches prevent a summary-statistic calculation from being mistaken for the trial’s own analysis.

Finally, the study highlights the importance of reporting multiplicity, missing-data procedures, and sample-size rationale. Several dose comparisons and a secondary outcome require a clear plan for interpretation. The registry record’s planning illustration shows how required sample sizes depend on the effect chosen for detection, but it is not evidence of the trial’s original design assumptions. These statistical details shape how strongly the results can be interpreted and how precisely they answer the study question.

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.

The primary outcome is measured during an Environmental Exposure Chamber challenge. This controlled setting supports a focused comparison under allergen exposure, but the endpoint does not itself establish what happens in other settings or over a longer period. The registry record reports the primary timeframe as 6 months and does not provide longer-term outcome results.

The primary results are based on a Full Analysis Set defined as participants receiving at least one dose, with endpoint data described as available at Visit 7. The registry record does not report the number of missing endpoint observations by group, the reasons for missingness, or the method used to handle missing data. It is therefore not possible from the record to assess how incomplete outcome data may affect the estimates.

The statistical plan is incompletely described in the registry record. The analysis model’s covariates, any multiplicity adjustment, interim analyses, and the original sample-size justification are not reported. The recalculated comparisons rely on approximate variability derived from posted standard errors and are unadjusted; they should not be treated as a replication of the sponsor’s ANCOVA. The sponsor’s own analysis takes precedence where the results differ.

There is also no reported threshold for a clinically important change in the symptom-score area under the curve. Without that context, the magnitude of a difference cannot be translated into a judgment about clinical importance using the registry results alone. The safety summaries are descriptive and the serious-event counts are small; the record does not establish causality from these counts.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of 100IR, 300IR, 500IR Sublingual House Dust Mite Tablets in Allergic Rhinitis Environment Exposure Chamber Model — NCT01527188.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2025-02-04.
• 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

NCT01527188 is a completed, randomized, quadruple-masked, parallel-group Phase II study of 100 IR, 300 IR, and 500 IR sublingual house dust mite allergen tablets versus placebo for allergic rhinitis due to house dust mite. The registry reports enrollment of 355 participants.

The primary outcome was change from baseline to the end-of-treatment period in the 4-hour area under the curve of the Rhinitis Total Symptom Score during an allergen chamber challenge, at 6 months. The sponsor’s ANCOVA results show negative dose-versus-placebo estimates, with the 500 IR interval below zero and the 100 IR and 300 IR intervals including zero. The record also lists one secondary outcome covering the later 2-hour period of the challenge.

The registry record does not report the original sample-size justification, multiplicity approach, detailed missing-data handling, or full model specification. Those omissions and the chamber-based endpoint constrain interpretation of the posted results.