PK and ECG Determinations Following 8 Weeks of HyBryte Treatment for Cutaneous T-Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PK and ECG Determinations Following 8 Weeks of HyBryte Treatment for Cutaneous T-Cell Lymphoma (NCT05380635), a na phase 2 study. The primary outcome is Electrocardiograms (ECG).

2. Clinical Question

The brief summary also describes an objective of assessing blood levels of hypericin during 8 weeks of treatment. However, the registry information summarized in this record does not provide numerical pharmacokinetic results. The study is thus framed around systemic exposure and ECG monitoring, but the posted results do not establish the observed exposure or the frequency of qualifying QT events. The listed secondary outcomes concern lesion response measured using the Composite Assessment of Index Lesion Disease Severity (CAILS) score. Those outcomes are also not accompanied by numerical results in the registry record.

3. Trial Design

This completed study is identified as a Phase 2a trial of systemic pharmacokinetic and serial ECG determinations following 8 weeks of HyBryte treatment. Its model is single group, with no allocation to competing treatment groups and no masking. The registry lists an enrollment of 9 participants and identifies cutaneous T-cell lymphoma/mycosis fungoides as the condition studied.

The intervention description specifies topical HyBryte (0.25 % hypericin) applied to lesions, followed by visible light 18-24 hours later. Treatment was scheduled twice a week, with at least 2 calendar days between sessions, over 8 weeks. The light treatment was to start at 5 J/cm^2. These details describe the planned intervention regimen in the registry; they do not show how many sessions each participant actually received or whether the regimen was modified.

The primary ECG endpoint has a 10-week timeframe, while the intervention is described as lasting 8 weeks. The registry does not explain the timing of assessments within that timeframe, the visit schedule, or the method used to summarize serial ECG measurements. It also does not report specific pharmacokinetic sampling times or assay details.

The trial is marked completed, with a start date of 2022-05-09 and a primary completion date of 2022-08-16. Completion status indicates the registry status of the study; it does not by itself establish that all planned analyses or results were reported. The record lists 5 outcome measures, while the described secondary outcomes include participant-level response and lesion-level response or complete response based on CAILS improvement. Numerical results for these outcomes are not reported in the registry record.

Because the design has a single treated group, the study can describe observations among enrolled participants if those results are reported, but it cannot estimate a randomized treatment contrast against an untreated or alternative-treatment group. The registry record does not report the protocol, the sample-size justification, or details of any interim analyses.

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

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Electrocardiograms (ECG), measured over 10 weeks.

The primary endpoint concerns the occurrence of ECG QT interval changes during standard HyBryte photodynamic therapy. The registry defines a qualifying change as any occurrence of a QT interval >500 ms or a change in QT interval >60 ms. The measure is a count of participants, and its stated timeframe is 10 weeks.

ECG monitoring is used to characterize cardiac electrical measurements during the treatment period. A threshold-based endpoint converts repeated ECG observations into an indicator of whether a participant met a prespecified criterion at any point in the relevant timeframe. This can be useful when the clinical question concerns the presence of a potentially notable measurement rather than an average change across all measurements. That is a general explanation of this type of endpoint, not a claim about what happened in this study.

The threshold definition combines two criteria: an absolute QT interval threshold and a change-from-baseline threshold. The record does not specify how repeated readings were handled, how baseline was defined, whether readings were centrally reviewed, or whether any confirmatory measurement was required. Such details affect interpretation because a count of participants with at least one qualifying observation depends on assessment frequency and measurement procedures.

No participant count or other numerical result for this endpoint is reported in the registry record. Therefore, it is not possible to determine from the posted results whether any participant met either criterion, how often ECGs were assessed, or how precisely the event frequency was estimated. The endpoint definition indicates what the investigators intended to assess; it is not itself an outcome finding.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study uses a single-group design. In general, a single-group study measures outcomes among participants who receive the intervention without assigning a separate control group. It can describe what was observed in the enrolled group, provided the outcome data are reported. It does not create a randomized comparison, so it cannot isolate the effect of treatment from other explanations for observed changes. In this registry record, allocation is listed as not applicable and masking as none.

What does the primary endpoint count?

The primary measure is a count of participants meeting an ECG criterion. The registry defines a qualifying finding as any occurrence of QT interval >500 ms or a change in QT interval >60 ms during a 10-week timeframe. A participant-level count differs from a count of ECG readings: if a participant has repeated qualifying readings, the participant-level measure may still count that person once. The record does not explain the operational rules for repeated observations, so the exact handling cannot be confirmed.

Threshold endpoints are often used to make a repeated measurement clinically interpretable by defining in advance what constitutes a qualifying event. This is a general description of the method. The endpoint does not, by itself, convey the size or duration of every QT change, and a participant who does not cross a threshold may still have smaller changes. The posted registry information does not include the actual ECG results or enough detail to evaluate their distribution.

Why do missing analysis details matter?

Repeated measurements require decisions about baseline, timing, data quality, and how to handle readings that are absent or difficult to interpret. These choices can affect a threshold-based participant count. The registry record does not report the ECG schedule, baseline definition, adjudication process, or missing-measurement rules. It also does not report an analysis population definition. Without these details, readers cannot determine how the endpoint was derived or whether the stated timeframe was fully observed for every participant.

The record lists zero analyses. This indicates that no analysis entries are reported in the registry record; it does not establish why they are absent or whether analyses were conducted outside the registry. The primary endpoint result and numerical results for the secondary outcomes are not reported. Consequently, there is no reported estimate, confidence interval, or hypothesis-test result to interpret. A confidence interval is a statistical range that reflects uncertainty around an estimate under specified assumptions. It would help convey how imprecise an estimate may be, but no such interval is reported in the registry record.

How should the safety counts be read?

Counts of participants at risk identify the group denominator used in the safety listing, while affected counts indicate how many participants were recorded with an event in that category. The registry lists 9 at risk for serious adverse events and 0 affected, and 9 at risk for other adverse events and 3 affected. It lists 0 deaths. These counts are not a complete account of event type, severity, timing, duration, or attribution. The record does not list serious adverse event terms, and it does not describe the other adverse events in the information summarized for this analysis.

In general, adverse event counts describe observations during a defined study context; they do not automatically establish causality. A single group cannot distinguish events associated with treatment from events that might have occurred for other reasons. For a small enrolled group, counts also provide limited information about less common events. This general statistical point does not indicate that an unreported event occurred in this study.

What do planning calculations represent?

Sample-size illustrations based on an observed effect are planning scenarios, not observed power. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect defined as a stated fraction of the observed effect. Those assumptions describe hypothetical planning calculations and do not describe the actual single-group design. The registry record does not report the trial's own sample-size justification. Since no numerical primary outcome estimate is reported, readers should not treat a planning illustration as evidence that the trial had a particular probability of detecting an effect.

Over-dispersion is a general statistical concern when count data vary more than a simple model assumes; it can make uncertainty estimates too narrow if the model does not account for that extra variation. The primary outcome is defined as a participant count rather than a reported rate model, and the registry record does not describe an over-dispersion model or any model-based analysis. No statistical model should be inferred from the endpoint definition alone.

Finally, the three described lesion-response outcomes use CAILS improvement thresholds, including ≥50% improvement and a 100% improvement definition for complete response. These are outcome definitions, not analyses. The registry record does not report the statistical methods used to evaluate them, any adjustment for multiple outcomes, or numerical results. General methods such as confidence intervals, hypothesis tests, and multiplicity adjustment can only be interpreted when the analysis specification and results are available.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("HyBryte (0.25 % Hypericin)")
n      <- c(9)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  HyBryte (0.25 % Hypericin)  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, including a primary ECG outcome and secondary lesion-response outcomes. The secondary outcomes described include participant response among three treated lesions, the number of index lesions meeting a response definition, and the number meeting a complete-response definition. When several outcomes are examined, the chance of obtaining an apparently notable result across the full set can differ from the chance for any one prespecified outcome. This is the general issue of multiplicity.

The registry record does not report whether statistical tests were planned for these outcomes, whether any adjustment for multiple comparisons was intended, or how outcome priority was handled beyond identifying the ECG measure as primary. It lists zero analyses and gives no numerical results or p-values for the primary or secondary outcomes. Therefore, there is no reported multiplicity procedure to assess and no basis for interpreting a collection of outcome tests.

The record does not describe missing-data handling, the analysis population, or participant-level completeness for ECG and lesion assessments. It is not reported in the registry record whether every enrolled participant completed the planned treatment and follow-up, whether outcome data were unavailable for any participant, or how such cases would be handled. These details matter because exclusion or imputation decisions can change an analysis, especially in a small study. No missing-data method should be assumed from the fact that the study is marked completed.

The registry record also does not report a statistical analysis plan or interim-analysis procedures. Their absence from the registry information does not establish that none existed; their details are not reported in the registry record.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety listing records 9 participants at risk for serious adverse events, with 0 affected, and 9 participants at risk for other adverse events, with 3 affected. It also records 0 deaths. These are counts, not complete clinical descriptions. The registry record does not provide the terms, timing, duration, severity details, or treatment attribution for the 3 other adverse events. It lists no serious adverse event terms.

A count of 0 serious adverse events in this study means that none are recorded in this registry safety listing for the participants at risk. It does not demonstrate that serious events cannot occur, nor does it quantify risk beyond this study group. Similarly, the count of 3 participants with other adverse events does not identify what those events were or whether investigators considered them related to treatment. General interpretation of adverse event reports requires those details and the context in which events were collected.

The single-group design also limits comparative safety interpretation. Without a concurrent comparator, these counts cannot show whether events were more or less frequent than they would have been under another treatment or without the intervention. With 9 participants enrolled, the listed counts are a narrow description of this study, not a broad estimate of safety across a larger population.

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

The registry record establishes that a Phase 2a, single-group study of topical HyBryte was completed in participants with cutaneous T-cell lymphoma/mycosis fungoides. It describes a regimen involving 0.25 % hypericin ointment, visible light treatment 18-24 hours later, sessions twice a week at least 2 calendar days apart, and a planned treatment duration of 8 weeks. It also specifies an ECG endpoint assessed over 10 weeks and gives its QT thresholds.

Those study details do not establish what happened to participants. Numerical findings for the primary ECG endpoint, systemic hypericin levels, and the listed CAILS response outcomes are not reported in the registry record. The absence of those results is not evidence that no ECG changes or lesion responses occurred. No result should be inferred from a missing value.

The safety listing reports 0 participants with serious adverse events among 9 at risk, 3 with other adverse events among 9 at risk, and 0 deaths. These figures describe the posted registry counts. They do not identify the reported other events, establish causality, or rule out events not represented in the listing. Their interpretation is also constrained by the small single-group study design.

Even if the outcome results were available, this design would not compare HyBryte with a randomized control group. Differences over time within participants, if measured, could reflect treatment, natural variation, measurement processes, or other factors. A controlled comparison would be needed to estimate a relative effect in a way this design cannot provide. This is a general limitation of single-group evidence, not a claim about the participants' outcomes.

The study therefore contributes a defined monitoring question and an intervention regimen, along with limited posted safety counts. It does not provide enough numerical outcome information to estimate the frequency of the prespecified ECG findings, the systemic exposure, or the lesion response. It also does not establish comparative efficacy or a comprehensive safety profile.

14. Why This Trial Matters Statistically

This study is statistically relevant because it brings together repeated ECG monitoring, a threshold-defined participant-level outcome, pharmacokinetic assessment, and lesion-response measures in a single treatment group. Those features illustrate why careful separation of endpoint definitions from outcome findings is important. A registry may specify exactly what investigators intended to measure while still not reporting the values needed to answer the study question.

The ECG outcome is based on whether a participant had any qualifying QT finding over a stated timeframe. That form of endpoint makes the decision rule explicit, but its interpretation depends on how often ECGs were collected and how repeated readings were handled. The registry record does not provide those operational details or the event count. This emphasizes that measurement frequency and data handling are part of the statistical meaning of a repeated-measures endpoint, not merely administrative details.

The single-group design also demonstrates a distinction between describing observations and estimating a treatment effect. A study without a randomized comparator may be informative for monitoring and characterization, but it cannot provide a direct randomized contrast. A reader should not interpret a within-group observation as proof of causality, especially when numerical outcomes and analysis details are not reported.

Finally, the record highlights how small studies can be limited in precision and scope. Counts from 9 enrolled participants can describe only the reported experience in this group. They cannot provide a precise account of uncommon events, and without endpoint results there is no estimate or uncertainty interval to evaluate. The statistical importance of this record is therefore chiefly in its design and measurement definitions, alongside the clear distinction between registered objectives and reported findings.

15. 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 principal limitation for interpreting this specific study is that numerical results for the primary ECG endpoint are not reported in the registry record. The record therefore does not show how many participants met either QT criterion, nor does it provide an estimate or confidence interval. Numerical pharmacokinetic results and results for the described CAILS outcomes are also not reported.

The enrollment is 9, and the design is single group with no masking. There is no randomized control arm for comparison, so the study cannot estimate a treatment contrast against another intervention or a control condition. Small participant counts also restrict the precision and scope of any descriptive safety findings, even when those counts are posted.

Important analytic details are not reported in the registry record. These include the protocol, the sample-size justification, the analysis population, missing-data procedures, the timing and handling of serial ECG readings, the statistical analysis plan, and any interim-analysis procedures. The record does not explain how the 10-week ECG timeframe relates to individual assessment schedules or how incomplete assessments would be handled.

The safety listing provides counts but little event characterization. It reports 3 participants with other adverse events, but the event terms and further details are not available in the registry information summarized for this analysis. The serious adverse event count and death count are both 0; neither count can establish that risk is absent.

These limitations concern what can be learned from the registry record and study design. They do not establish that additional information was not collected or analyzed outside the registry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PK and ECG Determinations Following 8 Weeks of HyBryte Treatment for Cutaneous T-Cell Lymphoma — NCT05380635.
• Registry record last updated 2023-06-07; status last verified 2023-05.
• Results first posted 2023-06-07.
• 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.

19. Record Summary

NCT05380635 is a completed Phase 2a, single-group study titled PK and ECG Determinations Following 8 Weeks of HyBryte Treatment for Cutaneous T-Cell Lymphoma. The registry lists 9 participants, no masking, and no randomized allocation. The study evaluated topical 0.25 % hypericin ointment followed by visible-light treatment, with sessions scheduled twice weekly for 8 weeks.

The primary endpoint is the count of participants with a qualifying ECG QT interval finding during a 10-week timeframe, defined as QT interval >500 ms or a change in QT interval >60 ms. Numerical primary endpoint results are not reported in the registry record. Numerical pharmacokinetic and lesion-response results are not reported either.

The safety listing records 0 serious adverse events among 9 at risk, 3 participants with other adverse events among 9 at risk, and 0 deaths. Further details about the other adverse events are not reported in the registry information. The record supports a description of the study design and registered endpoints, but it does not provide numerical outcome findings for the primary question.