A Study of REPLAGAL® in Treatment-naive Chinese Participants With Fabry Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of REPLAGAL® in Treatment-naive Chinese Participants With Fabry Disease (NCT04974749), a na phase 3 study. The primary outcome is Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

The study’s stated main aim was to assess the safety of REPLAGAL. The registry lists efficacy and pharmacokinetics in the official title, but the primary outcome reported for this analysis is a safety count. That count describes participants who experienced at least one event meeting the serious adverse event criteria during the specified treatment and follow-up period.

Because the study has no control arm, the primary result describes events observed among participants receiving REPLAGAL; it does not estimate a difference between treatments. The registry reports 2 participants with serious treatment-emergent adverse events among 20 at risk in the REPLAGAL group. The record also reports 0 deaths. These counts are a description of the recorded safety experience, not a controlled estimate of treatment effect.

3. Trial Design

The registry describes a Phase 3, open-label, single-group study of REPLAGAL in treatment-naive Chinese participants with Fabry disease. The allocation field is NA, and masking is NONE. Enrollment is recorded as 20, and the study status is COMPLETED. The registry lists a start date of 2022-05-01 and a primary completion date of 2024-01-03.

Participants received REPLAGAL 0.2 milligrams per kilogram body weight by intravenous infusion every other week, from Day 1 (Week 0) up to Week 52. The brief summary describes repeated study-clinic visits during the study. The primary safety outcome covers the period from the start of study drug administration until 14 days after the end of treatment, up to Week 54.

With no comparator group, the design can describe outcomes occurring during treatment and follow-up, but it cannot provide a randomized, like-for-like comparison with another treatment or with no treatment. Open-label status means masking was not used; the registry record does not report further details about how outcome assessment was conducted.

The registry lists 29 outcome measures. Secondary outcomes include counts of participants with treatment-emergent adverse events, infusion-related reactions, positive anti-drug antibodies, positive neutralizing antibodies, clinically meaningful changes in laboratory parameters, vital signs, and electrocardiogram parameters. A secondary outcome also concerns change from baseline in estimated glomerular filtration rate at Week 52. These listed outcomes do not change the primary endpoint: the number of participants with serious treatment-emergent adverse events.

Details such as the planned sample-size justification, protocol-defined interim analyses, and a fuller statistical analysis plan are not reported in the registry record.

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: A total of 20 participants with Fabry disease were enrolled in this study to receive REPLAGAL for 52 weeks.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set included all participants in the ITT Set who received at least 1 dose of REPLAGAL.

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: Intent-to-treat (ITT) Set included all participants who signed the informed consent, were enrolled in the study, and received at least 1 study drug infusion (full or partial).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs), measured over From start of study drug administration up to 14 days after end of treatment (EOT) [up to Week 54].

The primary endpoint is the number of participants with serious treatment-emergent adverse events (TEAEs). It is a participant count: it records how many participants had an event meeting the endpoint definition, rather than the total number of separate events. The registry defines a TEAE as an event emerging at or after treatment initiation, or an existing event that worsened in intensity or frequency following exposure, through the end of the safety follow-up period.

The registry defines a serious adverse event as an untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolonged an existing hospitalization, caused persistent or significant disability or incapacity, was a congenital abnormality or birth defect, or was considered an important medical event. The definition applies whether or not the event was considered related to the investigational product.

Safety endpoints of this kind are used to describe clinically important events arising during treatment and the specified follow-up. Counting affected participants gives a direct account of how many people met the endpoint definition in the study population. It does not by itself establish that treatment caused an event. In this single-group study, the count also does not provide a comparative estimate against a control group. The registry’s outcome population is the Safety Analysis Set: participants in the ITT Set who received at least 1 dose of REPLAGAL.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level safety outcome summarized as a count: whether a participant had a serious treatment-emergent adverse event during the defined observation period. The registry reports the number meeting the endpoint and the number at risk for the REPLAGAL group. This is a descriptive summary, not an estimate of a treatment contrast, because the study is recorded as single-group and has no comparator.

What does a participant count represent?

A participant count classifies each person according to whether the endpoint occurred. It differs from an event count: one participant can experience multiple events, while a participant-level count records that person as meeting the endpoint. The registry’s primary outcome is explicitly the number of participants with serious TEAEs. The total number of serious events is not reported as this endpoint.

The reported 2 participants with serious TEAEs and 18 in the other category account for the group’s reported safety status among 20 at risk. These categories describe the endpoint classification; they are not randomized treatment arms. The registry also reports 0 deaths. A count of zero for deaths is limited to that recorded outcome and observation context; it is not evidence that no other serious events occurred.

How is a serious TEAE defined?

The registry defines a TEAE as an event emerging at or after initiation of treatment, or a pre-existing event that worsened in intensity or frequency after exposure, through the end of safety follow-up. A serious adverse event is defined by outcomes or clinical importance: death, life-threatening status, inpatient hospitalization or prolongation of hospitalization, persistent or significant disability or incapacity, congenital abnormality or birth defect, or another important medical event. The definition applies whether or not the event is considered related to the investigational product.

These definitions determine which events contribute to the primary endpoint. They do not mean that every counted event was caused by the study drug. The registry does not report an event-by-event causal assessment for the primary count.

What does the observation window cover?

The primary outcome timeframe begins with study drug administration and continues to 14 days after the end of treatment, up to Week 54. The treatment schedule ran from Day 1 (Week 0) up to Week 52, with infusions every other week. The specified follow-up window is relevant when interpreting the count: events outside the recorded timeframe are not represented by this endpoint.

What can be inferred without a control group?

In general, a controlled comparison helps separate differences between treatment groups from differences that could arise from participant characteristics, background event occurrence, or chance. This study has no control group, so the primary count describes the observed safety experience in the REPLAGAL group without estimating a between-group difference. It does not support a causal comparison with another treatment or with no treatment.

In general, uncertainty around a count-based estimate may be described with an interval or a statistical model, but the method and assumptions matter. The registry does not report a confidence interval or statistical test for this primary outcome. No inferential estimate should be read into the reported counts alone.

How should the planning illustrations be understood?

The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. The assumptions also distinguish total event counts for time-to-event tables from participants per arm for other outcomes. Those hypothetical planning assumptions do not change the actual single-group study design and are not observed power. Numeric planning estimates are not reported in the registry record.

More detailed methods—including the planned statistical model, handling of missing outcome data, and any adjustment for multiple outcome testing—are not reported in the registry record. Thus, the primary safety result is interpreted as the posted descriptive participant count, not as a result from an undocumented inferential procedure.

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("REPLAGAL")
n      <- c(20)
events <- c(2)
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  REPLAGAL  20  2  10.0  1.2  31.7  2.8  30.1  3.0  30.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 29 outcome measures, including the primary serious TEAE count and secondary safety, antibody, laboratory, vital-sign, electrocardiogram, and renal-function outcomes. When many outcomes are considered, multiplicity can matter: in general, testing several hypotheses can increase the chance of observing a nominally notable result by chance. Whether and how to address that issue depends on the prespecified analysis plan. Adjustment for multiplicity, endpoint hierarchy, and any confirmatory testing strategy are not reported in the registry record.

The record lists 0 analyses. It does not provide a statistical analysis plan for the primary count, a confidence interval, or a hypothesis test. Consequently, the primary result is treated as descriptive rather than as a reported significance finding.

Missing-data methods are not reported in the registry record. The primary outcome population is defined as the Safety Analysis Set, which included all participants in the ITT Set who received at least 1 dose of REPLAGAL. The registry does not report a definition of the ITT Set, the handling of participants with incomplete safety follow-up, or whether any primary outcome data were missing.

The outcome timeframe extends from the start of study drug administration through 14 days after the end of treatment, up to Week 54. Without details about event ascertainment and missing observations, it is not possible to assess from the registry record whether follow-up was complete for every participant. These omissions limit interpretation of the precision and completeness of the reported count, but they do not alter the count as recorded.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ectopic pregnancy (5.0%), sepsis (5.0%).

The primary safety result is a participant count. The registry reports 2 participants with serious treatment-emergent adverse events among 20 at risk in the REPLAGAL group. It also reports 18 in the other category and 0 deaths. The observation period ran from the start of study drug administration through 14 days after the end of treatment, up to Week 54.

“Serious” follows the registry’s definition, which includes specified consequences such as life-threatening events or hospitalization, as well as other important medical events. The definition applies whether or not an event was considered related to the investigational product. A counted serious TEAE should therefore not automatically be interpreted as caused by REPLAGAL.

The registry lists ectopic pregnancy and sepsis among the top serious terms, each at 5.0%. The record does not give further event-level detail in the registry record for this endpoint. The terms and percentages should be read as reported, not as a separate estimate of treatment effect.

Because the study has no comparator arm, these figures describe observed safety experience and cannot show how the count compares with another treatment or background occurrence. The registry does not report a confidence interval for the primary count.

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

The result describes serious treatment-emergent adverse events recorded in a single-group study of REPLAGAL in treatment-naive Chinese participants with Fabry disease. The registry reports 2 participants with serious TEAEs among 20 at risk, with the outcome followed from treatment initiation through 14 days after the end of treatment, up to Week 54. It also reports 0 deaths.

This count does not establish that REPLAGAL caused the events. The registry’s serious adverse event definition applies whether or not an event was considered related to the investigational product. The count also does not establish how the safety experience would compare with another treatment, because the study has no comparator group and is not randomized.

The result does not describe the total number of serious events, their duration, or the circumstances of every event. The listed serious terms include ectopic pregnancy and sepsis, each at 5.0%, but additional event-level details are not reported in the registry record. The primary endpoint is the number of participants meeting its definition, not a comprehensive account of all aspects of safety.

The record does not report a confidence interval or statistical test for the primary count. It therefore does not quantify the precision of the estimate through an interval or support a statistical conclusion based on a reported test. The outcome population is the Safety Analysis Set, defined as participants in the ITT Set who received at least 1 dose of REPLAGAL; details about missing safety data are not reported.

In general, a single-group safety count can describe what was observed during a study, while a controlled design is needed to estimate a comparative difference under the design’s assumptions. The posted data should be interpreted within the study’s population, treatment schedule, and follow-up period, not as a comparison or a conclusion about outcomes outside those conditions.

14. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical-trial statistics: a safety count can be informative as a description of observed events even when it cannot estimate a treatment difference. The registry’s primary endpoint records the number of participants with serious treatment-emergent adverse events. Its meaning depends on the event definition, the population included in the analysis, and the observation period.

Here, the registry defines serious events using clinical criteria that include death, life-threatening events, hospitalization, disability or incapacity, congenital abnormality or birth defect, and important medical events. It defines treatment-emergent events by their timing or worsening after exposure. These operational definitions make clear what the endpoint counts, while also underscoring that serious events are not necessarily judged related to treatment.

The single-group, open-label design provides a setting in which to report safety experience during REPLAGAL treatment and follow-up. It does not provide a like-for-like control comparison. Recognizing that limitation prevents a descriptive count from being mistaken for a causal estimate or a comparative risk measure.

The registry also lists a broad set of secondary safety and other outcomes, alongside the primary endpoint. In general, multiple outcomes require careful interpretation because the analysis plan determines how evidence across outcomes is assessed. The registry record does not report a multiplicity strategy, missing-data procedures, or inferential methods for the primary count. Those details matter when readers assess what conclusions the record can support.

Statistically, the key lesson is to match the claim to the design and endpoint: the posted result is a participant count from a defined safety population and timeframe. It is not a randomized comparison, a measure of total event burden, or a substitute for unreported precision and analysis details.

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 design limitation for interpreting the primary result is the absence of a comparator arm. The registry identifies the study as single-group, with allocation recorded as NA and masking as NONE. The reported safety count therefore has no concurrent control result against which to compare it. It describes events in the REPLAGAL group but cannot estimate a between-group difference.

The registry reports enrollment of 20 and 20 participants at risk for the primary safety outcome. The primary analysis population is defined as the Safety Analysis Set, comprising participants in the ITT Set who received at least 1 dose of REPLAGAL. How the ITT Set was defined and how incomplete follow-up or missing outcome information was handled are not reported in the registry record.

The primary endpoint counts participants with serious TEAEs, not the total number of serious events. The record gives the timeframe and definitions, but does not report event-level details sufficient to characterize duration, recurrence, or all circumstances surrounding the reported events. It lists ectopic pregnancy and sepsis among the top serious terms, each at 5.0%, and reports 0 deaths.

The registry does not report a confidence interval, statistical test, full statistical analysis plan, or multiplicity strategy for the primary outcome. It also does not report a sample-size justification for the trial. These missing details limit assessment of precision and the inferential framework, and should not be filled in by assumptions about customary practice.

Finally, the study population, treatment schedule, and follow-up period define the scope of the observed safety data. The record concerns treatment-naive Chinese participants with Fabry disease receiving REPLAGAL by intravenous infusion every other week up to Week 52, with safety follow-up through 14 days after end of treatment. The result does not directly establish what would be observed in other populations or under different treatment or follow-up conditions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of REPLAGAL® in Treatment-naive Chinese Participants With Fabry Disease — NCT04974749.
• Registry record last updated 2024-10-08; status last verified 2024-07.
• Results first posted 2024-10-08.
• 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

The registry record describes a completed Phase 3, open-label, single-group study of REPLAGAL in treatment-naive Chinese participants with Fabry disease. Participants received 0.2 milligrams per kilogram body weight by intravenous infusion every other week from Day 1 (Week 0) up to Week 52. Enrollment is recorded as 20.

The primary outcome was the number of participants with serious treatment-emergent adverse events, assessed from treatment initiation through 14 days after end of treatment, up to Week 54. The registry reports 2 participants with serious TEAEs among 20 at risk, 18 in the other category, and 0 deaths. Ectopic pregnancy and sepsis are listed among the top serious terms, each at 5.0%.

The record lists 29 outcome measures and 0 analyses. It does not report a confidence interval or statistical test for the primary count. The single-group result is descriptive and does not provide a controlled treatment comparison.