Phase 2a Evaluation of Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Patients With Primary Sclerosing Cholangitis (PSC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2a Evaluation of Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Patients With Primary Sclerosing Cholangitis (PSC) (NCT04480840), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events.

2. Clinical Question

The registry record describes a safety, tolerability, and pharmacokinetic evaluation, rather than a trial designed around a clinical efficacy endpoint. The primary outcome is a participant count. The accompanying comparison statistics express the difference in the proportion with at least one TEAE between each dose group and placebo. These comparisons describe the posted safety data; they do not by themselves establish that the study drug caused or prevented an event.

The posted results also include plasma concentration outcomes. Those measurements address drug exposure and are distinct from the primary safety question. The registry record lists an assessment at Week 12 and another at Week 24, but numeric results are posted for Week 12; Week 24 results are not reported in the registry record.

3. Trial Design

This was a randomized, double-blind, dose-ranging, placebo-controlled Phase 2a study with a parallel model. The registry record lists quadruple masking. It describes the study as multicenter and identifies participants with PSC and suspected liver fibrosis as the study population. The recorded enrollment was 121. The status is completed; the recorded start date is 2020-07-27 and primary completion date is 2024-02-26.

Five arms are listed: placebo and four PLN-74809 dose levels. Dose Level 1 was 40 mg for up to 12 weeks. Dose Levels 2 and 3 were 80 mg and 160 mg, respectively, for up to 12 weeks, with their descriptions stating that they followed Dose Level 1. Dose Level 4 was 320 mg for at least 24 weeks and up to 48 weeks, with its description stating that it followed Dose Levels 2 and 3. Placebo is described as being used in Parts 1, 2, and 3. These descriptions give the listed dose sequence and durations; other operational details are not reported in the registry record.

The safety outcome uses the Safety Population, defined in the record as all participants who took at least 1 dose of study drug. The group sizes for the posted primary outcome are 30 for placebo, 24 for Dose Level 1, 20 for Dose Level 2, 20 for Dose Level 3, and 27 for Dose Level 4. These are group-specific outcome denominators, not a reconstruction of participant flow. The record does not report the number randomized to each arm, withdrawals by arm, or reasons for discontinuation.

The original statistical analysis plan, allocation concealment procedures, and the identities of the masked parties are not reported in the registry record. The record also does not report the original sample-size justification. The planning illustrations available for interpreting observed effects use stated assumptions, but they are not the study's original design assumptions.

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: Safety Population included all participants who took at least 1 dose of study drug

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: Safety Population included all participants who took at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events, measured over Up to 40 weeks.

The primary endpoint is the number of participants with treatment-emergent adverse events, assessed up to 40 weeks. A participant is counted if an adverse event emerged or worsened in severity after the first administration of study drug. The registry record presents both the number affected and the number in the Safety Population for each arm.

This outcome is used to describe safety and tolerability during treatment. Counting participants with at least one event answers whether an event occurred for a participant, rather than how many separate events that participant experienced. As a result, this endpoint does not convey the total event burden, the duration or severity of every event, or whether an event led to stopping treatment. Those details are not reported as part of the primary endpoint description.

The posted comparison is a risk difference: the proportion of participants with a TEAE in a PLN-74809 dose group minus the proportion in placebo. A negative estimate indicates a smaller observed proportion in the dose group; a positive estimate indicates a larger observed proportion. This is a descriptive contrast of the recorded groups. Interpretation should account for uncertainty, the modest group sizes, the several dose comparisons, and the fact that the endpoint is a safety count rather than a measure of clinical benefit.

7. Results Posted in the Registry

• PLN-74809 Dose Level 1: 41.7% (10/24) versus 70.0% (21/30) on control; risk difference -28.3 percentage points (95% CI -54.0 to -2.7), risk ratio 0.60 (0.35–1.01); unadjusted two-proportion z-test p = 0.036.
• PLN-74809 Dose Level 2: 80.0% (16/20) versus 70.0% (21/30) on control; risk difference 10.0 percentage points (95% CI -14.0 to 34.0), risk ratio 1.14 (0.83–1.58); unadjusted two-proportion z-test p = 0.430.
• PLN-74809 Dose Level 3: 75.0% (15/20) versus 70.0% (21/30) on control; risk difference 5.0 percentage points (95% CI -20.1 to 30.1), risk ratio 1.07 (0.76–1.51); unadjusted two-proportion z-test p = 0.700.
• PLN-74809 Dose Level 4: 85.2% (23/27) versus 70.0% (21/30) on control; risk difference 15.2 percentage points (95% CI -6.0 to 36.4), risk ratio 1.22 (0.92–1.61); unadjusted two-proportion z-test p = 0.172.

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.

Assessment of PLN-74809 Total Plasma Concentrations at Week 12

• 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 deviations.
• Result:
  • PLN-74809 Dose Level 1: mean 638.71 versus 0.00 on control; difference 638.71 (95% CI 476.96 to 800.46), standardized effect d = 2.42; z-test p = <0.001.
  • PLN-74809 Dose Level 2: mean 843.06 versus 0.00 on control; difference 843.06 (95% CI 623.94 to 1,062), standardized effect d = 2.66; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for PLN-74809 Dose Level 1 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for PLN-74809 Dose Level 2 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry record lists total plasma concentration assessments at Week 12 and Week 24. Numeric outcome results are posted for Week 12, while Week 24 results are not reported in the registry record. The Week 12 values show a general increase in mean concentration across the active dose levels, alongside a placebo value of zero. The reported standard deviations indicate variation in concentration measurements within the active groups. The group sizes contributing to this outcome are not the same as those for the primary safety outcome, so these results describe a different analysis population and measurement.

These secondary outcomes concern pharmacokinetics: they describe measured plasma exposure rather than whether participants experienced TEAEs. They can provide context about exposure across dose levels, but they do not establish a relationship between exposure and an individual participant's adverse events. The registry record does not report an analysis linking concentration values to safety outcomes, nor does it report numeric Week 24 results.

The secondary information should carry less inferential weight than a prespecified primary analysis. The registry record lists multiple outcomes and the posted secondary comparisons have unadjusted p-values. A multiplicity adjustment or a hierarchy for interpreting secondary outcomes is not reported in the registry record. When multiple outcomes and comparisons are considered, unadjusted results are more susceptible to chance findings. They are best treated as descriptive or exploratory unless a prespecified analysis strategy establishes otherwise.

The Week 12 concentration pattern and primary TEAE counts answer different questions and should not be combined into a single conclusion about clinical benefit or overall safety. Plasma concentration is a measure of exposure; the primary endpoint is a participant-level indicator of a treatment-emergent event. The record supports describing each outcome on its own terms, but it does not establish that the concentration pattern accounts for the observed differences in TEAE counts.

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

• Assessment of PLN-74809 Total Plasma Concentrations at Week 12
• Assessment of PLN-74809 Total Plasma Concentrations at Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: each person either had at least one TEAE during the specified observation period or did not. The registry gives counts and group denominators, and the comparison statistics express the between-group difference in proportions. This approach makes the contrast interpretable in absolute terms: it describes how far apart the observed proportions are, rather than only expressing a relative comparison.

What does a risk difference express?

A risk difference is the event proportion in one group minus the event proportion in the comparison group. Here, the comparison is each PLN-74809 dose level against placebo. A value below zero means the observed proportion was lower in the dose group; a value above zero means it was higher. The estimate is based on the participants included in the posted outcome groups, so it may vary from the underlying difference that would be seen in a larger population.

For Dose Level 1, the reported estimate is -0.283. The other reported estimates are 0.1 for Dose Level 2, 0.05 for Dose Level 3, and 0.152 for Dose Level 4. These are unadjusted, group-level contrasts. They do not account for baseline characteristics or other covariates, and adjusted comparisons are not reported in the registry record. The record does not describe the method used in a prespecified analysis plan.

How should the confidence intervals be understood?

A confidence interval expresses uncertainty around an estimate under the method used to construct it. A narrower interval indicates greater precision, while a wider interval indicates less precision. For a risk difference, an interval spanning zero includes values consistent with no difference between groups. It can also include differences favoring either group. An interval entirely on one side of zero indicates that the range of values covered by that interval lies in one direction, but it does not remove concerns about study design, multiplicity, or generalizability.

The interval for Dose Level 1 lies below zero, while the intervals for Dose Levels 2, 3, and 4 include zero. This describes the uncertainty around the posted unadjusted comparisons. A confidence interval is not a range containing every plausible value, and it does not give the probability that a particular treatment effect is true. It should be read together with the estimate, the group counts, and the analysis context.

What does an unadjusted p-value add?

A p-value measures how unusual data at least as incompatible with a specified no-difference model would be, if that model and the statistical assumptions were correct. It is not the probability that the no-difference model is true, and it does not measure clinical importance. The posted p-values are unadjusted: they do not account for testing several dose groups against placebo. The registry record does not report whether a multiplicity adjustment was planned or used, so the p-values should not be treated as family-wise confirmatory evidence.

The confidence intervals and p-values answer related questions about the same unadjusted contrasts, but they are not independent confirmations. In particular, an unadjusted p-value alone does not indicate the likely size of a difference. The estimate and its interval give more direct information about direction and precision.

Why can small safety groups produce uncertain estimates?

With fewer participants, each outcome count has a larger influence on the group proportion. The resulting comparisons can be sensitive to a small change in the observed count, and confidence intervals may be wide. This matters for every dose group in this study, especially when the aim is to distinguish modest differences rather than large ones. The record does not report a design justification establishing the precision intended for the primary safety endpoint.

Finally, the endpoint counts participants with at least one TEAE rather than the number, severity, or duration of all events. This makes the measure straightforward to compare across groups, but it compresses varied event experiences into a single indicator. Serious adverse events are reported separately and should not be conflated with the broader TEAE endpoint. Interpretation of the count outcome should therefore remain specific to what it measures.

11. Confidence Intervals and Precision

The risk-difference confidence intervals show that the primary comparisons are estimated with appreciable uncertainty. The interval for Dose Level 1 is -0.540 to -0.027 around an estimate of -0.283. The intervals for Dose Level 2, Dose Level 3, and Dose Level 4 are -0.14 to 0.34, -0.201 to 0.301, and -0.060 to 0.364, respectively. These ranges are wide enough to include meaningfully different possible contrasts, particularly for the comparisons whose intervals cross zero.

For Dose Level 2, Dose Level 3, and Dose Level 4, zero lies within the reported interval. That means the data do not precisely distinguish those estimated contrasts from no difference under the interval method. It does not establish equivalence, and it does not show that the groups are identical. The Dose Level 1 interval lies below zero, but it is also broad, indicating uncertainty about the magnitude of the difference even though the interval is on one side of zero.

The participant counts contributing to the primary endpoint are 30 for placebo, 24 for Dose Level 1, 20 for Dose Level 2, 20 for Dose Level 3, and 27 for Dose Level 4. With groups of this size, estimates of event proportions and differences can be affected by a small number of participants. The registry record does not report a precision target or the original sample-size justification, so the study's intended ability to estimate safety differences cannot be assessed from that rationale.

Confidence intervals summarize sampling uncertainty under their statistical assumptions; they do not include every source of uncertainty. They do not address potential bias, missing outcomes, multiplicity, or whether the Safety Population represents the intended clinical population. The registry record does not report missing-data methods or a multiplicity procedure. Consequently, precision should be judged alongside those limitations rather than from interval width alone.

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 participants per arm, not total participants, because the primary endpoint and the listed secondary outcomes are not time-to-event outcomes. The planning illustration assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For each illustration, the effect to detect is a stated fraction of the observed effect. The trial's original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes an illustrative group size per arm for a design that would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and assumptions were correct. The 90% power column uses a higher chance of detection under those same planning conditions and therefore generally requires more participants per arm. These figures are planning calculations, not observed power; they do not tell how much power this completed trial actually had.

The rows for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect are scenarios, not separate study results. A smaller effect is harder to distinguish from chance variation, so detecting a smaller effect generally requires more participants. The values are conditional on the observed estimate being a useful basis for planning, which may be uncertain when the original groups are small. They should not be read as a recommendation for a future study or as evidence that the original study was designed to those sizes.

For the Week 12 concentration comparisons, the same per-arm convention applies, but those calculations are based on continuous outcome summaries. The displayed planning assumptions remain illustrative; they do not replace the trial's unreported original design rationale.

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 = 0.700; treatment proportion p₁ = 0.417; average p̄ = 0.558.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7023 = 1.3764.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6731 = 0.5665.
4. n = (1.3764 + 0.5665)² / (-0.2833)² = 47.0, rounded up to 48 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 <- 0.7                          # control proportion
p1 <- 0.416666666666667                          # 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(4480840)
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 = 48 (80% power), 63 (90% power)
 75% of observed effect: n per arm = 83 (80% power), 111 (90% power)
 50% of observed effect: n per arm = 182 (80% power), 243 (90% power)
power.prop.test: 47 
Simulated power at n = 48 per arm: 0.808 (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. Multiplicity, Missing Data and Analysis Populations

Several comparisons are presented for the primary outcome: each of four PLN-74809 dose levels is compared with placebo. The posted p-values are unadjusted. When multiple comparisons are made, the chance of at least one result appearing unusual under a no-difference model can increase. A prespecified multiplicity strategy may address that issue, for example by controlling the overall error rate or by defining a hierarchy of hypotheses. Such a strategy is not reported in the registry record, so no adjustment should be assumed.

The study also includes secondary pharmacokinetic outcomes. The record lists Week 12 and Week 24 concentration assessments, and it posts numeric Week 12 results. The registry record does not report a multiplicity plan across primary and secondary outcomes, or across the comparisons within those outcomes. As a result, unadjusted secondary p-values should be treated as exploratory rather than as a collection of confirmatory findings.

The primary Safety Population is defined as participants who took at least 1 dose of study drug. That definition clarifies who was included in the safety counts, but other analysis-population definitions are not reported in the registry record. The record does not provide a participant-flow account that explains exclusions, withdrawals, or differences between enrolled participants and the group denominators for each outcome.

Missing-data handling is not reported in the registry record. It is therefore unclear how missing event information, incomplete follow-up, or missing concentration measurements were handled in the analyses. The record also does not report whether any interim analyses were planned or conducted, or how the primary comparison method was prespecified. These omissions limit assessment of the statistical decision process and the potential for selective reporting.

Without the analysis plan, multiplicity approach, and missing-data rules, the posted statistics can be read as descriptive comparisons with uncertainty, but not fully audited against the original inferential strategy. This does not negate the recorded counts; it constrains how strongly the p-values and comparisons can be interpreted.

15. 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: cholangitis (5.0%), abdominal pain (4.2%), cholecystitis (4.2%), enterobacter bacteramia (3.7%).

Serious adverse events are listed separately from the broader primary TEAE outcome. The registry record reports 1 participant with a serious adverse event in placebo, Dose Level 1, Dose Level 2, and Dose Level 4, and 0 in Dose Level 3. The corresponding numbers at risk are 30, 24, 20, 27, and 20, respectively. No deaths are listed in any of the five groups.

The record also lists Cholangitis at 5.0%, Abdominal Pain at 4.2%, Cholecystitis at 4.2%, and Enterobacter bacteramia at 3.7% among the serious adverse event terms. The registry record does not specify the denominator or group allocation associated with these term percentages in the posted summary, so they should not be assigned to a particular arm based on this information alone.

These counts are descriptive and do not establish whether an event was caused by study drug. Rare serious events are difficult to compare reliably in groups of this size, and no formal between-group serious-event analysis is reported in the registry record. The serious-event figures should also not be mistaken for the primary TEAE counts, which include the broader category of treatment-emergent adverse events.

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

The primary results describe the number of participants with at least one TEAE in each study group and the unadjusted differences in event proportions between each dose level and placebo. The observed count was lower in Dose Level 1 than in placebo, while the counts in Dose Levels 2, 3, and 4 were higher than in placebo. The reported confidence intervals and p-values add information about uncertainty, but the group sizes are limited and several comparisons are considered.

The results do not establish that PLN-74809 caused, prevented, or changed the likelihood of an adverse event. Randomization supports comparison of assigned groups, but interpretation also depends on how the trial was conducted, outcome follow-up, missing data, and the prespecified analysis. Several of those details are not reported in the registry record. In particular, the unadjusted comparisons do not account for multiple dose-versus-placebo tests.

The findings also do not establish a clinical benefit. The primary endpoint is a safety count, and the posted secondary results measure plasma concentration. No primary efficacy outcome is described in the registry record. A concentration pattern is not itself evidence that a treatment improves a clinical outcome, and it should not be interpreted as a surrogate for benefit without supporting evidence.

The serious adverse event counts are small, and the record does not provide a formal inferential comparison for them. Their observed distribution is informative as a safety description, but it cannot reliably exclude uncommon risks. Similarly, the absence of deaths listed in the groups does not establish that a treatment is free of risk.

The appropriate reading is therefore limited and specific: the record provides group-level safety counts, unadjusted contrasts with confidence intervals, and Week 12 exposure measurements. These data can inform understanding of what was observed during this study, but they do not settle the causal interpretation, comparative safety across dose levels, efficacy, or safety in populations beyond those studied.

17. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between an observed count and a precise estimate of a treatment-group contrast. Each arm has a modest number of participants, and the primary outcome counts whether each participant experienced at least one TEAE. A difference in a few participant outcomes can therefore materially affect the estimated group proportions and their contrast.

The dose-ranging structure creates several simultaneous comparisons with placebo. That offers descriptive information across dose levels, but it also makes multiplicity important. The Dose Level 1 interval lies below zero while the other dose-level intervals include zero; because the p-values are unadjusted and the registry record does not report a multiplicity plan, the contrast should be treated cautiously rather than as a definitive isolated finding.

The record also distinguishes safety from pharmacokinetics. Concentration measurements describe exposure, while the primary outcome describes participants with a treatment-emergent event. Keeping these measures conceptually separate prevents an exposure pattern from being mistaken for evidence of clinical benefit or a direct explanation for adverse-event differences.

Finally, the planning illustrations help show how sample-size needs depend on the effect a future study seeks to detect. They use explicit assumptions but do not reveal the rationale for the original trial. This distinction is important: retrospective planning from observed effects is not the same as prospective design, and the apparent precision of an observed estimate should not be mistaken for a study's intended statistical power.

18. 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 registry record does not report a full statistical analysis plan, the original sample-size justification, allocation concealment details, missing-data methods, or a multiplicity strategy. Without these, it is not possible to determine whether the posted comparisons follow a prespecified inferential approach or how incomplete follow-up affected the results.

The primary endpoint counts participants with any TEAE and does not summarize event frequency per participant, duration, severity, or the relationship of individual events to treatment. Serious adverse events are listed separately, but the record does not report a formal comparison or the group allocation behind the listed serious-event term percentages. The small group sizes also limit precision for uncommon events.

The dose levels were described in parts with specified sequences and different treatment durations. Consequently, the arm comparisons should be interpreted in the context of the study's listed structure and follow-up periods; the record does not provide enough detail to assess the effects of those features on exposure time or comparability. The registry record does not report participant flow or reasons for discontinuation.

Only Week 12 concentration results are posted numerically, despite the registry listing an assessment at Week 24. The record does not report a statistical analysis linking pharmacokinetic measurements to safety outcomes. These gaps limit interpretation of the overall exposure and safety relationship. The multicenter setting is recorded, but the number or characteristics of participating sites are not reported in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Phase 2a Evaluation of Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Patients With Primary Sclerosing Cholangitis (PSC) — NCT04480840.
• Registry record last updated 2026-01-23; status last verified 2026-01.
• Results first posted 2026-01-23.
• 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.

22. Record Summary

NCT04480840 is a completed randomized, double-blind, dose-ranging, placebo-controlled Phase 2a study of PLN-74809 in participants with PSC and suspected liver fibrosis. The registry record describes a parallel model, quadruple masking, and enrollment of 121. The recorded study dates are 2020-07-27 and 2024-02-26 for start and primary completion.

The primary outcome was the number of participants with TEAEs up to 40 weeks in the Safety Population. Posted counts and unadjusted risk-difference comparisons show variation across the four dose levels relative to placebo, with confidence intervals reflecting substantial uncertainty. Serious adverse events and deaths are reported separately. Week 12 total plasma concentration results are posted; numeric Week 24 results are not reported in the registry record.

The record does not report the original sample-size justification, multiplicity approach, missing-data methods, or full statistical analysis plan. Accordingly, the posted results are best interpreted as descriptive safety and pharmacokinetic findings, not as a definitive assessment of clinical efficacy or causal treatment effects.