Severe Renal Disease Study in Fabry Patients Treated With Fabrazyme: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Severe Renal Disease Study in Fabry Patients Treated With Fabrazyme (NCT00837824), a randomized phase 2 study. The primary outcome is Time to Clinically Significant Progression of Cardiac Disease, Cerebrovascular Disease, and/or Death Among Fabry Patients With Severe Kidney Disease.

2. Clinical Question

The registry identifies this as a dose-ranging study, with the stated aim of determining appropriate treatment at a biweekly dose of either 1 mg/kg or 3 mg/kg in patients with severe renal disease. The primary outcome combines clinically significant cardiac progression, cerebrovascular progression, and death into a time-to-event measure. The record does not describe the detailed criteria used to classify progression as clinically significant.

The clinical question therefore concerns both whether an event occurred and when it occurred after treatment began. The posted result is especially limited for comparing the regimens: only one participant had a primary clinical event during the study period, and that event was in the lower-dose group. The registry record does not report a comparative estimate or uncertainty interval for the difference between groups. The study's early termination and small enrollment are important context for interpreting that absence.

3. Trial Design

This was a Phase 2, randomized, open-label, parallel-group, multiple-dose study. It compared Fabrazyme 1.0 mg/kg every 2 weeks with Fabrazyme 3.0 mg/kg every 2 weeks. Masking was not used. The sponsor was Genzyme, a Sanofi Company. The study began in 2002-12, and primary completion was recorded as 2003-08.

The registry lists an enrollment of 20 and says that 120 was the original sample size. It also states that the trial was terminated early due to inadequate study design. Thus, the enrolled population was smaller than the original planned sample size. The registry record does not report the details of the design concern, a sample-size justification, or whether the planned allocation was changed during the study.

Randomization is intended, in general, to make treatment groups comparable at the time of assignment by using a chance-based process. It does not ensure that small groups will be balanced on every characteristic. Open-label means treatment assignment was not masked; the registry does not describe procedures for limiting the influence of knowledge of treatment assignment on outcome assessment.

The arm descriptions specify the two dosing regimens, and the study used a parallel structure rather than switching participants between doses. The adverse-event results list 11 participants at risk in the 1 mg/kg group and 9 in the 3 mg/kg group. The primary outcome results record an event count of one in the 1 mg/kg group and zero in the 3 mg/kg group. Those outcome entries do not provide a full account of follow-up or censoring by arm.

The study also lists plasma globotriaosylceramide (GL-3) as a secondary outcome. Its measurement results are not reported in the registry record. A detailed protocol, the randomization method, treatment adherence, and the study's statistical 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: Because the study was ended early only 20 patients from 9 sites were randomized into this study using a 1:1 randomization scheme to receive biweekly infusions of either 1 mg/kg (11 patients) or 3 mg/kg (9 patients) of Fabrazyme.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population-consisted of all 20 patients enrolled in the trial. The original sample size was 120 patients. Due to early termination, only 20 patients were enrolled in this trial. No imputation of data was performed. During the 7 months study period, only 1 patient had a clinical event in the Fabrazyme 1 mg/kg treatment arm.

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 Time to Clinically Significant Progression of Cardiac Disease, Cerebrovascular Disease, and/or Death Among Fabry Patients With Severe Kidney Disease, measured over 7 months.

The primary endpoint is time to clinically significant progression of cardiac disease, cerebrovascular disease, or death among patients with Fabry disease and severe kidney disease. The timeframe is 7 months. The record says that time to event was measured from the first Fabrazyme dose to the event date. During the study period, one participant had a clinical event: a stroke in the 1 mg/kg group.

A composite endpoint combines more than one type of event into a single outcome. In general, this can capture several clinically relevant ways a participant's condition may progress, rather than focusing on only one event type. A time-to-event endpoint also retains information about when an event occurs, rather than recording only whether it occurred by the end of follow-up. These are general properties of such endpoints; they do not establish that the component events are equally frequent or equally consequential in a particular trial.

The registry record does not specify the detailed thresholds for clinically significant cardiac or cerebrovascular progression, nor does it describe the handling of participants who had no event during observation. The posted primary results give one event and a value of 35.0 days for the 1 mg/kg group; the 3 mg/kg group has no event value reported. The record does not provide a comparative time-to-event estimate or confidence interval. With so few events, the posted result offers little information for estimating a difference between regimens.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a time-to-event outcome represent?

A time-to-event outcome records the time from a defined starting point until an event of interest occurs. For this trial, the starting point was the first Fabrazyme dose, and the event was clinically significant progression of cardiac disease, cerebrovascular disease, or death. The stated observation timeframe was 7 months. The registry reports one event, a stroke, in the 1 mg/kg group, with a time to event of 35.0 days.

In general, time-to-event methods can use information from participants who have not experienced the event by the end of their observed follow-up, or whose follow-up ends earlier. Such participants are often described as censored. The registry record does not provide participant-level follow-up or censoring details, so the follow-up experience cannot be reconstructed from the posted summary. The record also does not state the specific method used to compare event times.

Why is a group comparison not available?

The primary endpoint is treated in the record as a count-other outcome, and the record says that values are missing or not estimable for a two-arm comparison. The primary results list one event and 35.0 days in the 1 mg/kg group, while the 3 mg/kg group has no event value. The registry lists no analyses. Therefore, no comparative estimate, confidence interval, or p-value is available to interpret.

In general, an inferential comparison uses a statistical model or test to estimate how outcomes differ between groups while accounting for the data structure and assumptions. A single observed event provides very limited information about the distribution of event times or the contrast between groups. It does not support a precise estimate merely because the event occurred in one group. No alternative analysis should be assumed when the registry does not report one.

How should confidence intervals be understood?

In general, a confidence interval communicates the uncertainty around an estimated effect under the method's assumptions. It is not a guarantee that the true effect lies in the interval, and it does not by itself establish clinical importance. The registry record gives no confidence interval for the primary comparison. Readers therefore cannot use the posted primary outcome to assess the numerical precision of a comparative effect.

Likewise, a p-value is a measure derived under a statistical model and a specified null hypothesis; it is not the probability that a treatment works or that a result occurred by chance. No primary-comparison p-value is reported in the registry record. The event counts alone do not substitute for a reported test or model.

What can the planning illustrations tell readers?

Planning sample sizes are different from observed outcomes. In general, a sample-size illustration asks how many participants might be needed under specified assumptions to detect an effect with a chosen power and significance level. It is a planning exercise, not a measure of the probability that this completed study detected an effect. The registry record describes illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says that time-to-event illustrations use a total number of events, while other illustrations use participants per arm.

Because the primary outcome is based on one event and the two-arm comparison is not estimable, any planning illustration based on the observed effect should be read cautiously. It cannot repair the limited information in the trial's observed data. Such values are not observed power and should not be described as the study's achieved ability to detect a difference. The registry record does not report the trial's own sample-size justification or the assumptions used when the original sample size was set.

Why does over-dispersion matter for some outcomes?

In general, over-dispersion occurs when count data vary more than a statistical model assumes. If a model underestimates that variation, its standard errors may be too small and its confidence intervals too narrow. This issue can matter when analyzing counts, but the registry record does not report a count model or an over-dispersion assessment for this trial. It should therefore be treated only as a general statistical consideration, not as a feature known to have affected these results.

What do the secondary outcome and analysis records add?

The registry lists plasma GL-3 as a secondary outcome, but its results are not reported in the registry record. The record lists no analyses. It therefore does not establish which statistical methods, if any, were used to evaluate this outcome, nor does it report a multiplicity adjustment. A multiplicity adjustment is, in general, a way to account for the increased chance of a false-positive finding when several hypotheses are tested. The number and relationship of planned tests, and any adjustment strategy, are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies an intent-to-treat population consisting of all 20 participants enrolled. It states that no imputation of data was performed. In general, an intent-to-treat analysis keeps participants in their assigned groups regardless of later treatment changes, but the registry record does not describe the analysis procedures in enough detail to establish how every participant was handled for every outcome. It does not report the extent or pattern of missing outcome data.

The trial was terminated early due to inadequate study design. The registry says the original sample size was 120 and that 20 participants were enrolled. It does not report a sample-size justification, a revised enrollment target, or the statistical consequences anticipated from ending enrollment early. No interim analyses are reported in the registry record.

Plasma GL-3 is listed as a secondary outcome, but its results are not reported in the registry record. The record lists no analyses, and it does not describe a prespecified testing hierarchy or multiplicity adjustment. In general, testing multiple outcomes or hypotheses can increase the chance of a false-positive result if each is evaluated without accounting for the number of tests. That is a general concern; it is not evidence that any particular multiplicity problem occurred in this study.

The primary outcome has only one reported clinical event, and a two-arm comparison is described as not estimable. No comparative confidence interval or p-value is reported. Thus, the missing inferential results cannot be recovered from the event summary alone. The registry also does not report detailed censoring information, reasons for missing measurements, or a method for handling missing time-to-event data.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (18.2%), pyrexia (11.1%), sepsis (11.1%), urinary tract infection (11.1%), atrial flutter (9.1%).

The registry reports serious adverse events for 11 participants at risk in the 1 mg/kg group and 9 at risk in the 3 mg/kg group. Serious adverse events affected 4 participants in the 1 mg/kg group and 1 in the 3 mg/kg group; the total is 5 of 20. Other adverse events affected 10 participants in the 1 mg/kg group and 9 in the 3 mg/kg group; the total is 19 of 20. These are counts of participants affected, not a comparative statistical analysis.

The registry lists atrial fibrillation at 18.2%, pyrexia at 11.1%, sepsis at 11.1%, urinary tract infection at 11.1%, atrial flutter at 9.1%, and coronary artery occlusion at 9.1% among the top serious-event terms. The denominator and whether participants could contribute to more than one listed term are not reported in the registry record. Death counts are also not reported in the registry record.

In general, adverse-event counts describe events recorded during observation; they do not alone establish that treatment caused an event or permit a reliable comparison between regimens. Interpretation also depends on event definitions, timing, follow-up, and the number of participants observed. Those details are not fully reported for these results.

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

The posted results describe a small, early-terminated study of two Fabrazyme dosing regimens in patients with Fabry disease and severe renal disease. The primary outcome was time to clinically significant cardiac progression, cerebrovascular progression, or death over 7 months. One event, a stroke, was reported in the 1 mg/kg group, at 35.0 days. No event value is reported for the 3 mg/kg group, and no two-arm estimate is available.

These observations do not provide a precise estimate of how the regimens differ. The registry record reports no comparative effect estimate, confidence interval, or p-value, and says that values for a two-arm comparison are missing or not estimable. A single event cannot establish a dependable pattern in event timing or frequency. Conversely, the absence of a reported event in one group is not proof that the group had no risk or that the regimens were equivalent.

The adverse-event counts are descriptive as well. The registry records serious adverse events in both treatment groups and other adverse events in nearly all participants, but those counts alone do not establish cause or comparative safety. The record does not report death counts, and the denominator details for the listed serious-event percentages are not reported.

The trial's early termination and enrollment of 20, compared with the original sample size of 120, further limit what can be learned from the posted results. The registry states that termination was due to inadequate study design but does not report further details. The secondary outcome of plasma GL-3 is listed without results, and no analyses are posted.

In general, clinical-trial results should be interpreted in light of the question, the design, the amount of outcome information, and the precision of estimates. In this case, the registry supports a description of the reported event and adverse-event counts. It does not support a firm statistical conclusion about the comparative effect of the two dose regimens.

13. Why This Trial Matters Statistically

This study is statistically instructive because its intended comparison and its available outcome information differ substantially in scale. The registry says that the original sample size was 120, but the trial was terminated early and enrolled 20. For the primary time-to-event outcome, only one clinical event was reported. These registry entries make the distinction between a treatment contrast of interest and an estimable treatment effect especially important.

When event information is sparse, a group-level difference in observed counts can appear straightforward while remaining highly uncertain. In general, statistical inference depends not only on which group had an event, but also on the amount of follow-up, the distribution of event times, and the assumptions of the analysis. The registry does not provide a comparative model, uncertainty interval, or p-value for this endpoint. The record explicitly indicates that a two-arm comparison was not estimable.

The study also illustrates why a planning calculation cannot replace completed-trial evidence. Sample-size illustrations based on an observed effect are planning exercises, not observed power and not estimates of the certainty of a treatment effect. With only one primary event, the observed effect is an especially limited basis for planning. The registry record does not report the trial's own sample-size justification, and no such rationale should be inferred from the later illustration.

Finally, the record separates several kinds of information that should not be conflated: the primary clinical event, serious adverse-event counts, other adverse-event counts, and a listed secondary laboratory outcome. The posted information is not a complete inferential analysis across these outcomes. Recognizing these limits is central to reading early-terminated trials and sparse-event results without overstating what the data establish.

14. 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 states that the trial was terminated early due to inadequate study design, but it does not describe the specific design problem or how it affected the conduct or analysis. Enrollment was 20, while the original sample size was 120. The record does not explain the original sample-size rationale or report a revised target.

The primary endpoint combines cardiac progression, cerebrovascular progression, and death, but the record does not provide detailed criteria for clinically significant progression. It reports one stroke and a time to event of 35.0 days in the 1 mg/kg group. A primary result for the other group is not available, and the record says the two-arm comparison is not estimable. Detailed follow-up and censoring information are not reported.

The study was open-label, with no masking. The registry does not describe how outcome assessment was conducted or whether procedures were used to limit potential influence from knowledge of assignment. The randomization method and allocation procedures are also not reported in the registry record.

The secondary outcome, plasma GL-3, is listed without results. No analyses are posted. The registry record does not report a multiplicity strategy, details of missing data beyond stating that no imputation was performed, adherence information, or the timing and process of early termination. These omissions limit assessment of the intended analysis and the robustness of the posted results.

Safety summaries are also limited: death counts are not reported, and the denominator and overlap of participants for the listed serious-event percentages are not specified. These limitations constrain interpretation of both the primary comparison and the broader outcome record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Severe Renal Disease Study in Fabry Patients Treated With Fabrazyme — NCT00837824.
• Registry record last updated 2015-04-07; status last verified 2015-03.
• Results first posted 2009-02-05.
• 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.

18. Record Summary

NCT00837824 is a Phase 2 randomized, open-label, parallel-group, dose-ranging study of Fabrazyme in patients with Fabry disease and severe renal disease. It compared 1.0 mg/kg every 2 weeks with 3.0 mg/kg every 2 weeks. The trial began in 2002-12 and had primary completion in 2003-08. It was terminated early due to inadequate study design.

The registry reports 20 enrolled participants, compared with an original sample size of 120. The primary outcome was time to clinically significant cardiac progression, cerebrovascular progression, or death over 7 months. One stroke was reported in the 1 mg/kg group, with a time to event of 35.0 days; a two-arm comparison was not estimable. Plasma GL-3 is listed as a secondary outcome, but its results are not reported in the registry record. No analyses are posted.

Serious adverse events affected 4 of 11 participants at risk in the lower-dose group and 1 of 9 in the higher-dose group. Other adverse events affected 10 of 11 and 9 of 9, respectively. These descriptive results do not provide a precise comparative estimate.