Efficacy and Tolerability Study of Two Dose Regimens of CTP-543 in Adults With Alopecia Areata: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Tolerability Study of Two Dose Regimens of CTP-543 in Adults With Alopecia Areata (NCT03811912), a randomized phase 2 study. The primary outcome is Relative Change From Baseline in Severity of Alopecia Tool (SALT) Score at Week 24.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 2 study of two CTP-543 dosing regimens in adults with moderate to severe alopecia areata. The registry record lists triple masking. The arms were CTP-543 8 mg BID and CTP-543 16 mg QD, and both treatment schedules lasted 24 weeks. The study is listed as completed.

The registry record lists an enrollment of 57. For the primary endpoint, the efficacy population included participants who received study drug and had at least one post-treatment SALT assessment. It lists 29 participants in the 8 mg BID arm and 28 in the 16 mg QD arm for that outcome. Participants were analyzed according to their randomized regimen. The record does not explain whether participants who did not meet the efficacy-population definition were excluded for a particular reason, or how missing endpoint measurements were handled.

The study start date is 2019-03-21, and the primary completion date is 2019-11-21. The registry describes the purpose as evaluating efficacy and tolerability of once-daily versus twice-daily dosing. Both regimens involved active CTP-543; the matching placebo tablets formed part of the dosing schedules. Thus, the posted primary comparison addresses the two schedules against each other. The registry record does not report the original sample-size justification, the planned statistical analysis details, or the process used to assign participants to regimens beyond stating that allocation was randomized.

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: 70 participants were screened out of which 57 participants who experienced an episode of hair loss due to alopecia areata were enrolled and randomized to receive CTP-543 8 mg twice daily (BID) or CTP-543 16 mg once daily (QD).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy Population included all participants who received study drug and had at least 1 post-treatment SALT assessment. Participants in the efficacy population were analyzed according to their randomized dosing regimen.

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: Randomized Population included all the randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Relative Change From Baseline in Severity of Alopecia Tool (SALT) Score at Week 24, measured over Baseline, Week 24.

The primary endpoint was relative change from baseline in Severity of Alopecia Tool (SALT) score at Week 24, with baseline and Week 24 as the stated time points. SALT is a quantitative assessment of scalp hair loss. Its scale ranges from 0, representing no hair loss, to a maximum score of 100, representing complete hair loss.

Relative change was defined as 100 multiplied by the difference between baseline SALT and follow-up SALT, divided by baseline SALT. With this formula, a reduction in SALT from baseline gives a positive relative change, while an increase gives a negative relative change. The endpoint therefore expresses change relative to each participant’s baseline score, rather than only the raw point change on the SALT scale.

A continuous score can retain information across the range of measured changes, whereas a threshold outcome groups participants according to whether they crossed a specified cut-off. The registry lists several secondary outcomes based on SALT changes and thresholds, but the primary result addressed the average relative change at Week 24. The primary endpoint population was restricted to participants who received study drug and had at least one post-treatment SALT assessment. The record does not report further details about the measurement process or how baseline values were treated when calculating relative change.

7. Results Posted in the Registry

• CTP-543 16 mg QD: mean 18.00 versus 46.40 on control; difference -28.40 (95% CI -46.75 to -10.05), standardized effect d = -0.80; z-test p = 0.002.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: it is a relative change in SALT score, summarized by a mean for each dosing arm. A mean describes the central average of the values included in the analysis. It can be useful for comparing groups, but it does not reveal whether most participants had changes close to the mean or whether the average reflects a wide range of individual outcomes.

What does the standard deviation describe?

General statistical explanation: a standard deviation describes how spread out individual observations are around their group mean. A larger standard deviation indicates greater dispersion on the measured scale, while a smaller one indicates that observations are more concentrated around the mean. It is not itself an estimate of the uncertainty in the mean. That uncertainty also depends on the amount of information in the group and on assumptions used by the analysis.

The posted standard deviations are 38.21 for CTP-543 8 mg BID and 32.32 for CTP-543 16 mg QD. The study reports 29 and 28 participants, respectively, for the primary endpoint. These arm summaries show substantial spread in relation to the group averages, so the means should not be treated as descriptions of every participant’s change. The registry record does not provide a participant-level distribution, such as quantiles or the number of observations at different values.

How should the mean difference be read?

The posted contrast is defined as the 16 mg QD mean minus the 8 mg BID mean. Its estimate is -28.4. A negative estimate means that the first arm in that stated contrast had a lower average relative change than the second. Since positive relative change corresponds to lower SALT from baseline under the endpoint formula, direction and interpretation should be kept tied to the endpoint definition. The contrast is not a ratio and should not be read as a relative percentage difference between the two arm means.

The posted unadjusted p-value is 0.002. General statistical explanation: a p-value describes how compatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor is it a measure of the size or practical importance of a difference. The registry record does not state the exact test used for this comparison or whether the p-value was adjusted for examining multiple outcomes or comparisons. It should therefore be described as the posted unadjusted result, not as evidence that all possible analyses would give the same inference.

Why does the analysis population matter?

The efficacy population was defined as participants who received study drug and had at least one post-treatment SALT assessment. Participants were analyzed according to randomized dosing regimen. This definition combines a post-randomization requirement (receiving study drug and having a follow-up assessment) with the original randomized assignment for grouping. General statistical explanation: excluding participants after randomization can affect the balance created by random assignment if the reasons for exclusion are related to prognosis or outcome. The registry record does not report the number or characteristics of people who did not enter the efficacy population, so the extent of any such effect cannot be assessed from these registry entries.

The registry also lists secondary outcomes, including SALT changes at other visits, threshold-based SALT responses, and satisfaction with hair coverage. It lists four secondary outcomes and six outcome measures, but no analyses are listed for the posted outcome record. The record does not state a hierarchy of hypotheses, a multiplicity adjustment, or a prespecified analysis plan. General statistical explanation: when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase unless the testing strategy accounts for multiplicity. The registry information does not establish whether or how such control was planned or used.

What cannot be reconstructed from the summaries?

Group means, standard deviations, sample sizes, and a reported contrast do not provide the underlying participant-level data. They cannot show the shape of the outcome distribution, identify influential observations, or establish whether model assumptions were checked. The registry record does not report the method used to estimate the interval, the confidence level, covariate adjustment, treatment of missing measurements, or interim analyses. Those details should remain unknown rather than being filled in from common practice.

General statistical explanation: when variability differs across groups or the outcome distribution is skewed, the validity and precision of a simple mean comparison can depend on how the analysis handles those features. Over-dispersion is a concern when the observed variability is greater than a statistical model expects; ignoring it can make uncertainty appear smaller than it is. This is a general principle, not a finding that over-dispersion occurred in this study. The registry record does not report diagnostic checks or enough information to assess such assumptions.

10. Confidence Intervals and Precision

The posted comparison gives a mean difference of -28.4, with interval endpoints of -46.75 and -10.05. The registry record does not identify the confidence level or the method used to construct this interval. It is therefore appropriate to describe the reported range and its direction, while avoiding an unsupported label such as a particular confidence level.

General statistical explanation: an interval estimate conveys uncertainty around an estimated quantity. A narrower interval indicates more precision under the method’s assumptions; a wider interval indicates less precision. An interval is not a range containing every participant’s outcome. It concerns uncertainty about the group contrast, and its interpretation depends on the analysis method and its assumptions.

Both endpoints of the reported interval are negative, consistent with the direction of the estimated contrast, defined as 16 mg QD minus 8 mg BID. The interval therefore places the estimated average difference below zero across its reported range. Its width also shows that the exact size of the contrast is not pinned down to a single value. The point estimate is not the only relevant quantity: the interval describes a range of values compatible with the posted analysis.

The arm standard deviations, 38.21 and 32.32, describe variability among observed relative changes, while the interval describes uncertainty about the contrast. These quantities answer different questions. The registry does not report intervals around each arm mean, and it does not provide participant-level data for examining the spread or shape of outcomes.

Precision should also be considered in context of the efficacy population, which included participants who received study drug and had at least one post-treatment SALT assessment. Missing-data handling and the number excluded from this population are not reported in the registry record. The reported interval consequently does not, by itself, resolve uncertainty about selection into the analysis population, the applicability of the estimate beyond the analyzed participants, or the effects of any unreported analysis choices.

11. 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 planning illustrations express sample size as participants per arm, not as total events. This is a continuous-outcome comparison, and the planning values use the observed mean difference as their reference effect. For planning at 100% of the observed effect, the illustrations give 25 participants per arm for 80% power and 33 participants per arm for 90% power. Planning for 75% of the observed effect gives 44 participants per arm for 80% power and 59 participants per arm for 90% power. Planning for 50% of the observed effect gives 98 participants per arm for 80% power and 131 participants per arm for 90% power.

General statistical explanation: power is the probability that a planned analysis will meet its chosen statistical criterion if a specified effect is present and the planning assumptions hold. The 80% column represents a design targeting an 80% chance of detecting the stated effect; the 90% column targets a 90% chance under the same general framework. Higher target power generally requires more participants for a given effect size.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect defined as the stated fraction of the observed effect. Smaller target effects require more participants in these illustrations. These figures are planning illustrations based on the observed effect, not observed power. The original trial’s own design assumptions and sample-size justification are not reported in the registry record, so the illustrations should not be treated as the trial’s planned enrollment calculation.

12. 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 = -28.400; pooled standard deviation σ = 35.441.
2. n = 2 × (1.96 + 0.842)² × 35.441² / -28.400² = 24.4, rounded up to 25 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 <- -28.4                      # observed difference in means
sigma <- 35.4410751940329                     # 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(3811912)
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 = 25 (80% power), 33 (90% power)
 75% of observed effect: n per arm = 44 (80% power), 59 (90% power)
 50% of observed effect: n per arm = 98 (80% power), 131 (90% power)
power.t.test: 25.4 
Simulated power at n = 25 per arm: 0.793 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary endpoint as relative change from baseline in SALT score at Week 24. It also lists secondary outcomes covering threshold-based SALT reductions, absolute SALT change at several visits, relative SALT change at several visits, and change in satisfaction with hair coverage. Four secondary outcomes and six outcome measures are recorded. This identifies a set of outcomes, but it does not describe how they were prioritized or tested.

The reported p-value for the mean comparison is explicitly unadjusted. The registry record does not report whether the primary endpoint had a formal testing hierarchy, whether secondary outcomes were adjusted for multiplicity, or whether any adjustment method was used. General statistical explanation: testing multiple hypotheses can increase the chance of at least one small p-value arising by chance under a setting where all null hypotheses are true. A prespecified hierarchy or adjustment can address that issue, but the registry information does not establish whether either was part of this study’s analysis.

Missing-data details are also not reported in the registry record. The efficacy population included participants who received study drug and had at least one post-treatment SALT assessment. The record does not state how many randomized participants lacked a post-treatment assessment, why any assessments were absent, or how missing Week 24 values were handled. It does not report imputation, a sensitivity analysis, or another approach to missing outcomes. The effect of missing measurements on the posted estimate therefore cannot be assessed from these details alone.

The analysis population is described, and participants in it were analyzed according to randomized dosing regimen. The registry record does not report a separate intention-to-treat analysis or provide enough information to determine whether all randomized participants were included in another analysis. It also does not state whether any interim analyses were planned or conducted. These omissions should be treated as unreported details, not as evidence that a particular method was or was not used.

14. 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 non-serious adverse event terms

The posted serious adverse event figures list 0 participants affected in the CTP-543 8 mg BID arm, among 29 at risk, and 0 participants affected in the CTP-543 16 mg QD arm, among 28 at risk. Deaths are listed as 0 in each arm. These are counts for the groups and categories recorded in the registry; they do not establish that no adverse events of any kind occurred.

The record lists 23 participants with other adverse events in each arm, among 29 and 28 at risk, respectively. The “other” category is distinct from the serious adverse event figures. The registry record does not provide the terms for those other events in the registry record, their severity or duration, or whether participants experienced more than one event. No serious adverse event terms are listed.

These counts should be read as descriptive safety information for the study arms, not as a complete account of tolerability or as a formal statistical comparison. The registry record does not report a safety analysis plan or estimates comparing risks between regimens. The study’s stated purpose included evaluating tolerability, but the listed figures alone do not establish a broader safety profile.

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

The primary result describes a difference in average relative SALT change at Week 24 between two randomized CTP-543 schedules. The 8 mg BID arm had a mean relative change of 46.4, and the 16 mg QD arm had a mean relative change of 18.0. The posted contrast was -28.4 for 16 mg QD minus 8 mg BID, with a reported interval from -46.75 to -10.05 and an unadjusted p-value of 0.002. Under the endpoint’s formula, positive relative change reflects a reduction in SALT from baseline.

The result does not show that every participant had a change close to their arm’s mean. The posted standard deviations indicate variability, and the registry does not provide the individual observations or a distribution of responses. The comparison also does not establish that an individual would have the same outcome under either regimen; the study reports group-level summaries.

The endpoint is specific to relative SALT change at Week 24. It is not a measure of outcomes beyond that time point, and it does not answer every question about hair coverage or satisfaction. Although the registry lists secondary outcomes addressing other SALT time points and response thresholds, their numerical results are not part of the registry entries for this result. Results for those outcomes should not be inferred from the primary endpoint.

The comparison was between two active CTP-543 dosing regimens, with matching placebo tablets included in the dosing schedules. The registry record does not list a placebo-only arm in this comparison. It therefore does not directly quantify either regimen’s contrast with no CTP-543 treatment. Nor does this result alone establish effects in populations other than the adult chronic, moderate to severe alopecia areata population described in the record.

The efficacy population required receipt of study drug and at least one post-treatment SALT assessment. Because missing-data handling and the number excluded from the primary analysis are not reported, the result should be understood as applying to the analyzed population as defined, with uncertainty about how exclusions or missing values may affect interpretation. The reported comparison is one statistical result, not a complete account of efficacy, safety, or longer-term outcomes.

16. Why This Trial Matters Statistically

This study offers a direct randomized comparison of two schedules of the same study drug, rather than a contrast between a drug regimen and a placebo-only arm. That design makes the primary statistical question specific: how the average relative SALT change at Week 24 differed between CTP-543 8 mg BID and CTP-543 16 mg QD in the analyzed population. Clear identification of the contrast direction is important because the reported mean difference is defined as the once-daily arm minus the twice-daily arm.

The continuous primary endpoint preserves information about the size of change on a relative scale. The arm means, standard deviations, mean difference, interval, and unadjusted p-value provide different pieces of evidence: central outcomes, participant-level spread, estimated contrast, uncertainty around that contrast, and compatibility with a null model under the test assumptions. No single statistic replaces the others. In particular, a small p-value does not convey the size or precision of an effect by itself.

The registry’s efficacy-population definition is also statistically important. Requiring participants to have received study drug and at least one post-treatment SALT assessment means the primary analysis is not described simply as including everyone randomized. The record’s statement that participants were analyzed according to randomized regimen preserves the assignment grouping among those analyzed, but does not answer how people without a post-treatment assessment were handled.

Finally, the entry distinguishes posted results from planning illustrations. The sample-size illustrations use the observed effect under stated assumptions, while the original sample-size rationale is not reported. Keeping those purposes separate avoids interpreting a retrospective planning exercise as a feature of the original trial design or as evidence of observed power. Overall, the statistical value of the record lies in the explicit endpoint, arm summaries, and contrast, alongside clear recognition of what the registry does not report.

17. 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 comparison is reported for the efficacy population, defined by receipt of study drug and at least one post-treatment SALT assessment. The registry record does not state how many randomized participants were absent from this population, why they were absent, or how missing Week 24 measurements were handled. This limits assessment of whether the analyzed group represents all randomized participants.

The record reports group means and standard deviations but does not provide participant-level observations or fuller distributional summaries. It does not report the exact statistical test, the interval’s confidence level, covariate adjustment, model diagnostics, or sensitivity analyses. The unadjusted p-value is posted, but multiplicity methods and a testing hierarchy are not reported. The original sample-size justification and interim-analysis details are also not reported in the registry record.

The comparison concerns two CTP-543 dosing regimens at Week 24. The registry record does not list a placebo-only arm for this primary comparison, and the results described do not establish outcomes beyond the stated time point. Several secondary outcomes are listed, but numerical results for them are not included among these registry entries, limiting what can be said about other SALT measurements, response thresholds, or satisfaction with hair coverage.

For safety, the record includes counts for serious adverse events, deaths, and other adverse events, but does not provide the serious event terms, details of other events, duration, severity, or repeated events. These limitations concern the available registry information; they do not establish that the underlying study did not collect such information.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy and Tolerability Study of Two Dose Regimens of CTP-543 in Adults With Alopecia Areata — NCT03811912.
• Registry record last updated 2022-12-09; status last verified 2022-11.
• Results first posted 2022-12-09.
• 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.

21. Record Summary

The registry record describes a completed randomized, triple-masked, parallel-group phase 2 study of CTP-543 in adults with moderate to severe alopecia areata. Enrollment was 57. The study compared CTP-543 8 mg BID with CTP-543 16 mg QD, with both regimens lasting 24 weeks.

The primary endpoint was relative change from baseline in SALT score at Week 24. In the efficacy population, the posted mean relative changes were 46.4 for 8 mg BID and 18.0 for 16 mg QD. The posted mean difference for 16 mg QD minus 8 mg BID was -28.4, with interval endpoints -46.75 and -10.05 and an unadjusted p-value of 0.002.

The registry also lists secondary SALT and satisfaction outcomes and safety counts. Details of missing-data handling, multiplicity procedures, the original sample-size rationale, and several analysis methods are not reported in the registry record.