Study to Evaluate the Efficacy and Safety of CTP-543 in Adults With Moderate to Severe Alopecia Areata (THRIVE-AA2): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Efficacy and Safety of CTP-543 in Adults With Moderate to Severe Alopecia Areata (THRIVE-AA2) (NCT04797650), a randomized phase 3 study. The primary outcome is Percentage of Participants Achieving an Absolute Severity of Alopecia Tool (SALT) Score ≤20 at Week 24.

2. Clinical Question

The primary outcome is a threshold-based measure of scalp hair loss. It asks whether participants reached a specified SALT score by the assessment time, rather than measuring the average amount of change across every participant. The registry record also lists secondary questions about other SALT thresholds and changes, as well as participant and clinician assessments of hair satisfaction, severity, and improvement.

The comparison is between each CTP-543 dose group and placebo. It is not a direct comparison between the two doses. The randomized, parallel-group design supports comparing outcome frequencies across the assigned groups, while the placebo arm provides a reference for the same treatment period and endpoint definition.

3. Trial Design

THRIVE-AA2 was a Phase 3, randomized, quadruple-masked, parallel-group study with placebo control. The registry record names Concert Pharmaceuticals as the sponsor and reports enrollment of 517. The study is listed as completed. Its start date is 2021-06-10, and its primary completion date is 2022-06-08.

Three arms are described: placebo, CTP-543 8 mg BID, and CTP-543 12 mg BID. Participants received the assigned tablets orally twice daily for up to 24 weeks. The primary outcome was assessed at Week 24. The registry record’s efficacy population definition includes participants who were randomized and dispensed study drug during the treatment period; it does not simply describe every person enrolled.

Random allocation is intended to make treatment groups comparable on average, including with respect to factors that may affect outcomes, though chance imbalances can remain. Masking is intended to limit the influence of treatment knowledge on participants’ experiences and outcome assessment. The registry record identifies quadruple masking but does not specify which roles were masked or give the randomization procedure and any stratification factors.

The design permits two separate placebo comparisons: each dose group against placebo. It does not establish a direct randomized contrast between the 8 mg and 12 mg groups in the posted analyses. The number enrolled is a trial-level figure, whereas the primary outcome and safety summaries use their own analysis populations and denominators. Those counts should not be treated as interchangeable.

The registry record does not report the original sample-size justification or the assumptions used to plan the trial. It also does not report the detailed protocol, the statistical analysis plan, or whether interim analyses were planned or conducted. Those omissions limit what can be concluded about the original design choices from this record alone.

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: 671 participants were screened, out of which 517 participants who experienced moderate to severe hair loss due to alopecia areata were enrolled to receive CTP-543 or placebo.

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 were randomized in the study and dispensed study drug during the treatment period.

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: All randomized participants included all participants who were randomized in the study.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving an Absolute Severity of Alopecia Tool (SALT) Score ≤20 at Week 24, measured over Week 24.

The primary endpoint is the percentage of participants who achieved an absolute SALT score of 20 or less at Week 24. SALT is a quantitative assessment of scalp hair loss, with scores ranging from 0, meaning no scalp hair loss, to a maximum of 100, meaning complete scalp hair loss. A lower score therefore represents less scalp hair loss on this scale.

This endpoint converts each participant’s score into a yes-or-no outcome at a prespecified threshold: the participant either achieved the threshold or did not. The reported percentage describes how often that outcome occurred in each arm. It does not describe the average SALT score, the average change from baseline, or the distribution of individual changes.

A threshold endpoint can be useful when the question is whether participants reached a defined level, rather than how much their scores changed on average. It is also straightforward to compare between groups as a difference in outcome proportions. However, the threshold does not retain all the information in the underlying score: participants just on opposite sides of the cutoff are classified differently, while participants with quite different scores on the same side are grouped together.

The registry record defines the efficacy population as randomized participants who were dispensed study drug during the treatment period. It does not describe in this endpoint definition how missing Week 24 measurements were handled, so the displayed percentages should be interpreted in light of the stated analysis population and the missing-data details available in the record.

7. Results Posted in the Registry

• CTP-543 8 mg BID: 32.9% (82/249) versus 0.8% (1/127) on control; risk difference 32.1 percentage points (95% CI 26.1 to 38.2), risk ratio 41.82 (5.89–297.00); unadjusted two-proportion z-test p = <0.001.
• CTP-543 12 mg BID: 38.6% (49/127) versus 0.8% (1/127) on control; risk difference 37.8 percentage points (95% CI 29.2 to 46.4), risk ratio 49.00 (6.87–349.44); unadjusted two-proportion 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 of Participants Achieving an Absolute SALT Score of ≤10 at Week 24

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • CTP-543 8 mg BID: 24.9% (62/249) versus 0.0% (0/127) on control; risk difference 24.9 percentage points (95% CI 19.5 to 30.3); unadjusted two-proportion z-test p = <0.001.
  • CTP-543 12 mg BID: 26.8% (34/127) versus 0.0% (0/127) on control; risk difference 26.8 percentage points (95% CI 19.1 to 34.5); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for CTP-543 8 mg BID 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 proportion with the event is statistically higher for CTP-543 12 mg BID than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry record lists secondary outcomes spanning additional SALT thresholds, relative change in SALT, hair satisfaction, and participant and clinician ratings of improvement and severity. These measures address related but not identical questions. A threshold outcome asks whether a defined score was reached; a change score considers movement from baseline; ratings capture participant or clinician assessments.

The posted Week 24 SALT threshold outcome for SALT 10 or less points in the same broad direction across the three arms as the primary threshold result. That provides a related outcome perspective, but it is not an independent replication: it uses a closely related score, assessment time, and trial population. The other listed secondary measures broaden the clinical and reporting perspective, but the registry record does not give enough numerical detail in this record to characterize the direction and precision of every secondary result as a whole.

Secondary endpoints can help assess whether the primary pattern is accompanied by changes in other aspects of the measured condition. Agreement across different kinds of outcome can be informative, while disagreement may raise questions about endpoint definitions, timing, or measurement. These comparisons should remain endpoint-specific; a result on one threshold cannot be substituted for a result on satisfaction or perceived improvement.

Unadjusted secondary results carry less weight because testing multiple outcomes and time points increases the opportunity to find apparently notable results by chance. The registry record does not report a multiplicity adjustment or testing hierarchy. Accordingly, secondary findings are best treated as supportive or exploratory context unless a prespecified multiplicity strategy is documented, rather than as a collection of equally definitive confirmations of the primary outcome.

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

• Percentage of Responders on the Hair Satisfaction Participants Reported Outcome (SPRO) Scale at Weeks 12, 16, 20, and 24
• Percentage of Participants Achieving an Absolute SALT Score of ≤20 at Weeks 4, 8, 12, 16, and 20
• Relative Change in SALT Scores From Baseline at Weeks 4, 8, 12, 16, 20, and 24
• Percentage of Responders Assessed Using the Clinician Global Impression of Improvement (CGI-I) at Weeks 12, 16, 20, and 24
• Percentage of Responders Assessed Using the Patient Global Impression of Improvement (PGI-I) at Weeks 12, 16, 20, and 24
• Change in the Clinician Global Impression of Severity (CGI-S) Scores From Baseline at Weeks 12, 16, 20, and 24
• Change in the Patient Global Impression of Severity (PGI-S) Scores From Baseline at Weeks 12, 16, 20, and 24
• Percentage of Participants Achieving at Least a 75% and 90% Relative Reduction in SALT Score From Baseline at Weeks 12 and 24

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant either achieved SALT 20 or less at Week 24 or did not. For a binary outcome, the percentage in an arm is the proportion of participants meeting the stated condition in that arm. Comparing those proportions is different from comparing average scores or average score changes. It also means that the result depends on the chosen threshold and assessment time.

What does a risk difference express?

A risk difference subtracts the outcome proportion in one group from the outcome proportion in another group. It is an absolute contrast, rather than a relative ratio. The sponsor’s reported primary comparisons use risk differences for each CTP-543 dose against placebo. A positive estimate in this setting indicates that the threshold outcome was more frequent in the dose group than in the placebo group. The value is on the proportion scale; it should not be read as an odds ratio or as a change in SALT score.

Absolute contrasts are often easier to connect to the underlying arm proportions than relative measures. They retain a direct link to how frequently the endpoint occurred in each group. At the same time, a risk difference depends on the outcome frequencies in the particular study population and period. It does not by itself establish the result that would apply in a different population or follow-up setting.

Why use a Mantel-Haenszel analysis?

The registry record identifies the sponsor’s method as Mantel-Haenszel. In general, Mantel-Haenszel methods combine information across strata to estimate an association or contrast while accounting for the stratification used in an analysis. The registry record does not identify the factors defining any strata, so it is not possible to say from this record which factors were incorporated. The reported estimates and confidence intervals should therefore be understood as the sponsor’s analysis, not as an independently reconstructed adjustment for particular baseline characteristics.

The posted recalculations are simple, unadjusted comparisons from the group summary statistics. Such recalculations are useful as a check on the direction and broad scale of the posted arm differences. They do not reproduce an analysis that accounts for stratification or other model features. Since the registry record does not flag a discrepancy, the recalculation can be read as a descriptive cross-check; the sponsor’s reported analysis remains the registry’s formal comparison.

What do the p-values tell the reader?

A p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that the null model is correct, and it does not measure the probability that a result is due to chance in the everyday sense. Nor does a p-value describe the magnitude of a group difference or its practical importance. The sponsor’s primary p-values are reported as less than < 0.001 for both dose-versus-placebo comparisons. The recalculated unadjusted p-values are also reported as less than 0.001. These values address statistical evidence under their respective analyses, not the full interpretation of the endpoint.

Because the trial includes more than one dose comparison and the registry record lists multiple outcome measures, the interpretation of individual p-values also depends on how multiplicity was handled. The registry record does not report whether a multiplicity adjustment or a formal testing hierarchy was used. A set of unadjusted findings should not be interpreted as though every test were the sole prespecified question.

Why does over-dispersion matter?

For a binary endpoint, each person contributes an outcome classification, and the observed proportion varies across samples. In more complex outcome models, over-dispersion means that variability is greater than the model’s basic assumptions allow. If it is ignored where present, uncertainty estimates can be too narrow and statistical evidence can appear stronger than warranted. The registry record does not report an over-dispersion assessment for this binary primary endpoint. This is a general statistical consideration, not a claim that over-dispersion occurred in this trial.

The registry record also does not describe the model details beyond the named Mantel-Haenszel method, the handling of missing outcomes, or the original statistical plan. These details matter because analysis choices can affect estimates, standard errors, confidence intervals, and p-values. The available numerical results support interpretation of the stated group comparisons, but do not permit a full audit of every analysis decision.

11. Confidence Intervals and Precision

A confidence interval describes uncertainty around an estimated group contrast under the analysis and assumptions used. It is not a range containing every participant’s outcome, and it does not show the spread of individual SALT scores. A narrower interval indicates greater precision for the estimated contrast; a wider interval indicates more uncertainty about its size.

For the primary comparison of CTP-543 8 mg BID with placebo, the sponsor reported a risk difference of 0.31 with a 95% confidence interval from 0.25 to 0.37. For CTP-543 12 mg BID versus placebo, the reported risk difference was 0.36 with a 95% confidence interval from 0.27 to 0.45. Both reported intervals lie above zero, consistent with the sponsor’s reported p-values for those comparisons. The intervals still cover a range of plausible effect sizes under the analysis; they do not establish a single exact difference.

Confidence intervals do not account automatically for every source of uncertainty. Their interpretation depends on the analysis population, outcome definition, model, and treatment of missing data. They also do not resolve whether multiple comparisons were adjusted. The registry record does not report the missing-data method or a multiplicity strategy, so those aspects cannot be incorporated into an independent assessment of precision.

The uncertainty intervals for the sponsor’s adjusted comparisons are distinct from the simple unadjusted recalculations. An interval around one analysis should not be transferred to another analysis with a different method. Nor should the width of the interval be confused with the variation in outcomes among individuals. The confidence intervals quantify uncertainty in the group-level contrast, conditional on the analysis.

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 planning figures are illustrations based on the observed effect, not the original trial’s design calculation. For these binary outcome comparisons, the figures are participants per arm. The general sample-size note states that time-to-event illustrations use total events, but that convention does not apply to this primary endpoint.

The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They consider detecting a stated fraction of the observed effect: 100%, 75%, or 50%. The original trial’s own sample-size assumptions and justification are not reported in the registry record. The displayed planning figures are not observed power.

The 80% power column indicates the illustrative number of participants per arm associated with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and those assumptions were correct. The 90% power column makes the analogous illustration for a higher chance of detection. These are prospective planning concepts, not probabilities that the completed study produced a correct conclusion.

Read across a row to see the planning illustration for a given fraction of the observed effect, and compare the columns to see how the target power changes the required number per arm. Read across the effect scenarios to see how the assumed effect size changes the illustration. A smaller effect is harder to distinguish from random variation, so detecting it generally requires more participants. The calculations use the trial’s observed effect as their starting point, which means the illustrations inherit uncertainty in that observed estimate and should not be mistaken for a fresh trial design recommendation.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.008; treatment proportion p₁ = 0.329; average p̄ = 0.169.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5295 = 1.0377.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4782 = 0.4025.
4. n = (1.0377 + 0.4025)² / (0.3214)² = 20.1, rounded up to 21 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
p0 <- 0.0078740157480315                          # control proportion
p1 <- 0.329317269076305                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4797650)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 21 (80% power), 27 (90% power)
 75% of observed effect: n per arm = 30 (80% power), 39 (90% power)
 50% of observed effect: n per arm = 48 (80% power), 64 (90% power)
power.prop.test: 20.1 
Simulated power at n = 21 per arm: 0.915 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 formal primary analyses are Mantel-Haenszel risk-difference comparisons of each CTP-543 dose group with placebo. The registry reports the estimates, 95% confidence intervals, and p-values for those comparisons. The recalculations are simple unadjusted contrasts derived from the posted arm-level summaries; they provide a descriptive cross-check but do not reproduce the sponsor’s method.

The recalculations point in the same direction as the sponsor’s comparisons: the Week 24 threshold outcome was more frequent in each dose arm than in placebo. The estimates are not identical because the approaches are not the same. The registry record does not flag a discrepancy. The sponsor’s own analysis should therefore be read as the reported trial analysis, while the recalculation is useful for understanding the raw group-level contrast.

Neither approach answers questions that the registry record does not document, such as how missing Week 24 outcomes were handled or whether the testing strategy accounted for multiple outcomes and comparisons. The recalculation should not be described as the trial’s prespecified analysis, and the sponsor’s result should not be treated as proof that every secondary finding is reliable.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 16 outcome measures and 133 analyses. The primary endpoint is one of several outcomes, and the listed secondary measures include repeated assessments at different weeks and multiple score definitions. When many hypotheses are tested, the chance of at least one apparently unusual result can increase even if no true group differences exist. Statistical approaches such as a prespecified testing sequence or adjusted significance thresholds can address this concern, but the registry record does not report whether either approach was used.

The reported p-values should therefore be interpreted as results for the stated comparisons, not automatically as multiplicity-adjusted evidence across all outcomes, times, and arms. The record does not describe a hierarchy that would establish which secondary tests were confirmatory or how their interpretation depended on the primary test. This missing information limits the strength of claims based on individual secondary p-values.

The efficacy population is defined as randomized participants who were dispensed study drug during the treatment period. The record does not report how participants without a Week 24 measurement were treated, whether any imputation was performed, or whether sensitivity analyses assessed alternative missing-data assumptions. Missing outcomes can affect a percentage endpoint if the likelihood of missingness is related to treatment or outcome status. The available information does not establish whether that occurred.

The record also does not provide the complete statistical analysis plan, analysis timing, or details of any interim analyses. Those details would help establish which outcomes and analyses were prespecified and how deviations or missing observations were handled. Their absence is a reporting limitation; it is not evidence that a particular method was or was not used.

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: radius fracture (0.8%), osteoarthritis (0.8%), migraine with aura (0.4%), appendicitis (0.4%), pneumonia influenzal (0.4%).

The safety summaries use denominators that differ from the efficacy summaries, so each safety count should be read with its own at-risk group. Serious adverse events were reported for 0 participants in the placebo group, 3 in the CTP-543 8 mg BID group, and 2 in the CTP-543 12 mg BID group. Deaths were reported as 0 in each group. The record also reports other adverse events affecting 60 participants in the placebo group, 137 in the 8 mg BID group, and 67 in the 12 mg BID group.

The listed serious-event terms include radius fracture and osteoarthritis, each reported as 0.8%, and migraine with aura, appendicitis, and pneumonia influenzal, each reported as 0.4%. These are registry-listed terms and percentages; the record does not establish that a study drug caused any particular event. Event counts and percentages describe reported safety observations, not a causal attribution.

Safety comparisons require attention to the populations at risk, observation period, event definitions, and completeness of reporting. A difference in raw counts should not be interpreted without those details, and these summaries do not establish the full safety profile beyond the reported trial period.

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

The primary result describes the proportion of participants in each randomized group who reached SALT 20 or less at Week 24. The posted percentages and sponsor comparisons indicate that this threshold was more frequently reached in both CTP-543 groups than in the placebo group during the study period. The confidence intervals provide a range of uncertainty for the estimated group contrasts under the sponsor’s analysis.

This is a group-level finding, not a forecast for an individual. It does not say that every participant in a dose group reached the threshold, nor that no participant in the placebo group did. It also does not describe the size or timing of changes for participants who did not reach the cutoff. The binary endpoint compresses a range of SALT scores into a single classification.

The finding applies to the studied population and the specified Week 24 assessment. It does not establish the result for people outside the described adult population with moderate to severe alopecia areata, or for people with a different degree of scalp hair loss. The record reports treatment for up to 24 weeks and does not establish persistence after treatment or longer-term outcomes.

The result does not resolve every question about benefit and risk, the value of one dose relative to the other, or the experience of individual participants. The sponsor’s analyses compare each dose with placebo; they do not provide a direct dose-versus-dose conclusion. The registry record also does not report all analysis details needed to assess missing outcomes and multiplicity fully. No clinical decision can be drawn from the statistical comparison alone.

18. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition matters. SALT is a score ranging from no scalp hair loss to complete scalp hair loss, but the primary question is not about an average score. It is whether a participant reaches a specified absolute threshold by Week 24. The choice of threshold determines which score differences count as endpoint successes and which do not.

The design also makes clear why arm-level proportions and risk differences answer complementary questions. The percentages show how often the outcome occurred within each group; risk differences compare those proportions directly. Confidence intervals then add information about uncertainty in the estimated contrasts. Reading the three together is more informative than relying only on a p-value.

Separate placebo comparisons are reported for each CTP-543 dose. That distinction matters: the evidence for each dose versus placebo is not itself a test of whether the doses differ from one another. Likewise, a related SALT threshold can provide context without serving as an independent confirmation of the same finding.

Finally, this record demonstrates the boundary between posted results and full statistical documentation. It gives a named analysis method and sponsor estimates, but does not report the multiplicity plan, missing-data handling, original sample-size justification, or detailed analysis plan. Those omissions affect how broadly the results can be interpreted, even when the primary outcome pattern is clear in the reported group summaries.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint is a single threshold at Week 24. It does not preserve the full distribution of SALT scores, and it does not describe the average change from baseline or how participants changed over time. The registry record lists other SALT measures, but the primary result alone cannot answer those distinct questions.

The treatment period was up to 24 weeks. The registry record does not report whether the outcome differences persisted after that period, nor does it supply longer-term follow-up results. Thus the posted primary finding is limited to the stated assessment time and trial period.

The eligibility summary describes adults with 50% or greater scalp hair loss, but the registry record does not provide demographic or baseline clinical details in the information. The extent to which results apply to other patient groups cannot be assessed from the primary result alone. The efficacy population also excludes a simple interpretation of enrollment as the endpoint denominator: it is defined by randomization and dispensing of study drug.

Analysis details that can affect interpretation are not reported, including the handling of missing Week 24 outcomes, the original sample-size justification, and whether multiplicity was controlled. The record identifies the sponsor’s method but does not describe the strata or provide a full analysis plan. Safety summaries are counts during the study and do not by themselves establish causality or characterize risks outside the observed period.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of CTP-543 in Adults With Moderate to Severe Alopecia Areata (THRIVE-AA2) — NCT04797650.
• Registry record last updated 2023-07-03; status last verified 2023-06.
• Results first posted 2023-07-03.
• 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

NCT04797650 is the registry record for THRIVE-AA2, a Phase 3 randomized, quadruple-masked, parallel-group, placebo-controlled study of CTP-543 in adults with moderate to severe alopecia areata. The sponsor is Concert Pharmaceuticals. Enrollment is reported as 517, and the study status is completed.

The arms were placebo, CTP-543 8 mg BID, and CTP-543 12 mg BID, administered orally for up to 24 weeks. The primary outcome was the percentage achieving SALT 20 or less at Week 24. The sponsor reported Mantel-Haenszel risk-difference comparisons of each dose group with placebo, with confidence intervals and p-values.

The registry record lists additional outcomes and safety summaries, but does not report the original sample-size rationale, the detailed statistical plan, multiplicity handling, or missing-data methods. These limitations frame how far the posted comparisons can be interpreted.