This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Safety and Efficacy Study of Fabrazyme® Replacement Therapy in Patients With Cardiac Fabry Disease (NCT00140621), a non-randomized phase 4 study. The primary outcome is Percent Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00140621 |
| Phase | Phase 4 |
| Condition | Fabry Disease |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genzyme, a Sanofi Company |
| Results posted | Yes |
2. Clinical Question
Population
Patients with cardiac Fabry disease. The registry record reports enrollment of 6 participants; further eligibility details are not reported in the registry record.
Intervention
Agalsidase beta, described as replacement therapy, administered by intravenous infusion at 1 milligram per kilogram once every 2 weeks for up to 156 weeks.
Comparator
There was no randomized or concurrent comparison group. The study is described as non-randomized and single-group; the comparator is therefore not another treatment arm.
Primary question
What was the percent change from baseline to Week 156 in interventricular septum and left ventricular posterior wall thickness, assessed by echocardiogram? The numerical result is not reported in the registry record.
The clinical question is framed as a change over time among participants receiving agalsidase beta, not as a comparison of treatment effects between groups. The registry describes a baseline period of 4 weeks or less and a treatment period of 156 weeks. It identifies the primary endpoint as percent change from baseline in two measures of cardiac wall thickness at Week 156.
This endpoint can describe whether the measured wall thickness changed during the study period. However, a change observed within a single group does not, by itself, establish that treatment caused the change. Without a control group, changes could also reflect the course of disease, measurement variability, or other influences during follow-up. The registry record does not report a numerical endpoint estimate, confidence interval, or detailed account of participant-level measurements, so the size and direction of any observed change cannot be assessed from the record described.
3. Trial Design
This was a completed Phase IV, multicenter, open-label study with non-randomized allocation and a single-group model. Enrollment was 6. The registry lists Fabry disease as the condition and agalsidase beta as the intervention. The intervention description specifies intravenous administration at 1 milligram per kilogram once every 2 weeks, for up to 156 weeks.
The study summary describes a baseline period lasting 4 weeks or less, followed by a treatment period of 156 weeks. The registry lists the study start as 2005-07 and primary completion as 2012-08. These record dates describe the study timeline; they do not establish that every participant completed the full treatment period. Participant-level exposure and completion information are not reported in the registry record.
Open-label means that masking was not used, as the record states that masking was none. Non-randomized allocation and a single-group model mean that the design did not assign participants at random between treatment and control groups. There is no like-for-like control comparison in this study. Consequently, its primary question concerns within-group change from baseline rather than a difference in outcome between treatment groups.
The registry identifies the primary outcome as percent change from baseline in interventricular septum and left ventricular posterior wall thickness at Week 156. These measurements were assessed by echocardiogram. The primary outcome population is named EEP, but the meaning of that abbreviation and the criteria defining that population are not reported in the registry record.
The record also lists secondary outcomes concerning cardiac function and clinical symptoms, plasma GL-3 levels, and SF-36 scores at Week 156. It reports 7 outcome measures and 0 analyses. Those counts do not provide effect estimates or explain how the outcomes were analyzed. Details such as eligibility criteria, allocation procedures beyond non-randomization, treatment adherence, and the handling of withdrawals 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.
Overall Study
| Stage | Agalsidase Beta (Fabrazyme [Recombinant Form]) |
|---|---|
| STARTED | 6 |
| COMPLETED | 6 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: EEP.
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: Efficacy evaluable population (EEP) included all registered participants except those who had serious deviations from protocol compliance requirements, did not receive study drug, had no data available at baseline or after study drug administration, and who were found to have no condition in cardiac Fabry disease.
| Characteristic | Unit | Agalsidase Beta |
|---|---|---|
| Participants analysed | 6 | |
| Age, Continuous | years | 53.8 (SD 5.7) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 1 |
| Weight | kilograms (kg) | 58.50 (SD 9.24) |
| Height | centimeters (cm) | 156.63 (SD 7.20) |
| Left Ventricular Hypertrophy: No | participants | 0 |
| Left Ventricular Hypertrophy: Yes | participants | 6 |
| Globotriaosylceramide (GL-3) Accumulation in the Myocardium: No | participants | 0 |
| Globotriaosylceramide (GL-3) Accumulation in the Myocardium: Yes | participants | 1 |
| Globotriaosylceramide (GL-3) Accumulation in the Myocardium: Not Measured | participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156, measured over Baseline to Week 156.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percent change |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is percent change from baseline in interventricular septum and left ventricular posterior wall thickness at Week 156. The registry states that both thickness measures were assessed by echocardiogram and identifies the analysis parameter as a least-squares mean, with a 95% confidence interval as the dispersion measure. The numerical estimate and interval are not reported in the registry record.
In general, echocardiographic wall-thickness measurements describe aspects of cardiac structure. Expressing change as a percentage relates the follow-up measurement to the participant’s baseline measurement, while a least-squares mean is a model-based mean estimate. Its interpretation depends on the analysis model and the data included in that model; details of that model are not reported in the registry record.
A confidence interval describes statistical uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies in the interval, and it does not by itself establish clinical importance. Here, the record specifies the intended interval level but gives no interval endpoints or point estimate. Therefore, the precision and direction of the endpoint result cannot be evaluated from the registry record.
The endpoint is a measure of change within the study group. Because the study has no control group, it cannot directly separate change during treatment from change that might have occurred for other reasons. The endpoint can address the recorded measurement over time, but the design limits causal interpretation.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary outcome and its timeframe, but does not report the numerical result. It names the outcome as percent change from baseline in interventricular septum and left ventricular posterior wall thickness at Week 156, measured by echocardiogram. A least-squares mean and 95% confidence interval are specified as the result format, but neither the estimate nor the interval values are present. No direction or magnitude of change can therefore be stated from the record.
The study enrolled 6 participants and used a single-group, non-randomized, open-label design. With no control group, a baseline-to-follow-up change would describe what happened among participants measured over time, not what would have happened to comparable participants without the intervention. This distinction matters when interpreting any within-group change: it is not a treatment-versus-control effect and cannot alone establish that treatment caused the change.
The record states that the planned treatment period was 156 weeks, but it does not report how many participants contributed measurements at Week 156, how much follow-up each participant completed, or how missing measurements were handled. The label EEP is given for the primary population without a definition. The number enrolled therefore should not be treated as the number analyzed for the primary outcome.
A confidence interval, in general, helps convey the precision of an estimate. A narrow interval would indicate greater statistical precision than a wide interval, under the model assumptions; neither interval width nor statistical precision can be assessed because the interval values are not reported. The record also does not provide a p-value for the primary outcome. Statistical evidence about whether the endpoint changed, and the uncertainty around that change, cannot be reconstructed from the endpoint description alone.
The registry lists 7 outcome measures and 0 analyses. It also names secondary outcomes at Week 156, including cardiac function and clinical symptoms, plasma GL-3 levels, and SF-36 scores. The outcome descriptions are not accompanied by numerical results in the registry record for this interpretation. They therefore do not support conclusions about the direction, size, or precision of those outcomes.
Safety information is reported in participant counts for the study group. The record lists 1 participant affected by a serious adverse event among 6 at risk and 6 participants affected by other adverse events among 6 at risk. It names large intestine carcinoma at 16.7% among the top serious adverse event terms. The record does not report a death count. These safety entries should be read as the record’s adverse-event reporting, not as a controlled comparison or an estimate of treatment-attributable risk.
Overall, the available record describes the study question, treatment schedule, endpoint, and selected safety counts, but does not provide the primary endpoint estimate or its uncertainty. No conclusion about the observed cardiac wall-thickness change can be drawn from the endpoint specification alone. The small enrolled group and absence of a comparator also limit how far any within-group finding could be generalized or attributed to treatment.
9. Statistical Methods Explained
The primary outcome is continuous: percent change from baseline in two echocardiographic thickness measurements at Week 156. A continuous outcome can take values across a scale, rather than being limited to categories such as event or no event. The registry specifies a least-squares mean as the summary parameter and a 95% confidence interval as the measure of dispersion. It does not report the numerical estimate, confidence limits, or the underlying model details.
What a least-squares mean describes
In general, a least-squares mean is a model-based estimate of an average. Depending on the specified model, it may account for covariates or other design features. Its interpretation requires knowing the model, the analysis population, and the observations used. The registry record does not describe those details beyond naming the least-squares mean and identifying the primary population as EEP. The meaning of EEP is not reported in the registry record.
The endpoint is expressed as percent change from baseline. In general, this expresses a follow-up measurement relative to a baseline measurement, rather than reporting only the follow-up value. The registry does not give the exact calculation convention, whether the septum and posterior wall measurements were analyzed separately or combined, or the model used for the endpoint. These details should not be inferred from the endpoint title.
How to interpret a confidence interval
In general, a confidence interval gives a range of values compatible with the estimate under a statistical model and its assumptions. It helps readers judge precision: a wider interval indicates less precision than a narrower interval. The interval does not express the probability that an individual participant’s value falls within the range, nor does it itself measure clinical importance. Although the registry identifies a 95% confidence interval, it does not report the interval’s bounds. The precision of the primary estimate is therefore not assessable from the registry record.
What the single-group design permits
The study is described as non-randomized, open-label, and single-group. In general, a within-group analysis can describe observed change over time among participants with measurements. It does not provide a randomized comparison that estimates the difference between treatment and control groups. Changes over time may have multiple explanations, so a within-group estimate alone cannot isolate the effect of the intervention. The registry does not identify a comparator arm or a comparative treatment effect.
Open-label means there was no masking, according to the record. In general, lack of masking can matter for outcomes influenced by assessment or participant reporting. The primary endpoint is based on echocardiographic measurements, but the registry record does not describe measurement procedures, assessor masking, reproducibility, or quality control. No specific bias can be asserted from the available information; these are aspects that cannot be evaluated from the record.
Planning illustrations and observed results
The sample-size material is described as a planning illustration computed from an observed effect, not as the study’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. Those assumptions concern hypothetical planning, not the design of this single-group study. They do not establish that the study had a randomized two-arm design, and they are not observed power. The record does not report a protocol sample-size justification. No planning result should be read as an observed clinical outcome or as evidence of adequate power.
In general, a planning calculation estimates the sample size that might be needed under specified assumptions. Such an illustration depends on the target effect and analysis assumptions. It is not a substitute for an outcome estimate, confidence interval, or prespecified design rationale. The registry record does not provide enough information to assess whether its planning assumptions reflect the original protocol.
Why the sample and analysis details matter
Enrollment was 6, but the number contributing primary endpoint measurements is not reported in the registry record. The number enrolled is not necessarily the number analyzed at Week 156. In general, when a study has a small group, individual observations can have substantial influence on a group summary, and estimates may be imprecise. The actual precision cannot be judged without the numerical estimate, interval, and analysis sample.
The registry lists 0 analyses. This does not describe a statistical method, and it is not a substitute for a result. Details about model specification, assumptions, missing-data handling, multiplicity adjustment, and sensitivity analyses are not reported in the registry record. Without those details and the numerical endpoint output, readers cannot independently assess the calculation or determine how robust it is to analytic choices.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures, including a primary endpoint and secondary outcomes. The secondary outcomes named in the record concern cardiac function and clinical symptoms, plasma GL-3 levels, and SF-36 scores at Week 156. The registry reports 0 analyses, and it does not describe a statistical plan for controlling the chance of false-positive findings across multiple outcomes or comparisons. Whether multiplicity adjustments were planned or used is not reported in the registry record.
The primary population is labeled EEP, but the abbreviation is not defined. The registry does not explain which participants were eligible for the primary analysis or how deviations from the treatment schedule affected inclusion. The number enrolled is 6, but the number contributing primary endpoint data at Week 156 is not reported in the registry record.
Missing-data methods are not reported in the registry record. The record does not state how missing echocardiograms, incomplete follow-up, withdrawals, or other unavailable measurements were handled. It also does not report whether analyses used observed cases, imputation, or another approach. Without this information, it is not possible to judge whether the reported analysis, if any, represented all enrolled participants or a subset with available measurements.
In general, multiplicity matters because testing several outcomes can raise the chance that at least one appears statistically notable by chance. Missing-data methods matter because results can depend on which participants have measurements and why others are missing. These are general statistical considerations, not descriptions of methods used in this study. The registry record does not report enough information to determine how either issue was addressed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Agalsidase Beta | 1 | 6 | 16.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Agalsidase Beta | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Agalsidase Beta |
|---|---|---|
| Large intestine carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Agalsidase Beta |
|---|---|---|
| Nasopharyngitis | Infections and infestations | 5 of 6 |
| Palpitations | Cardiac disorders | 4 of 6 |
| Back pain | Musculoskeletal and connective tissue disorders | 3 of 6 |
| Anxiety disorder | Psychiatric disorders | 2 of 6 |
| Headache | Nervous system disorders | 2 of 6 |
| Pruritus | Skin and subcutaneous tissue disorders | 2 of 6 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 2 of 6 |
| Oedema | General disorders | 2 of 6 |
| Aspartate aminotransferase increased | Investigations | 2 of 6 |
| Chronic sinusitis | Infections and infestations | 1 of 6 |
Serious events with the highest arm-level rate: large intestine carcinoma (16.7%).
The registry lists 6 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it lists 6 participants at risk and 6 affected. These are participant counts for the single Agalsidase Beta group, not comparisons between treatment arms. The record lists large intestine carcinoma at 16.7% among the top serious adverse event terms.
Serious adverse events and other adverse events are reported as separate categories in the record. The counts describe participants affected, not necessarily the total number of distinct events. The registry entry does not provide event-level timing, duration, outcome, or an assessment of causal relationship to treatment. It does not report a death count; that information is not reported in the registry record.
These safety figures should be interpreted descriptively. The study has no control group, so the counts cannot establish whether an event occurred more or less often than it would have in a comparison group. The record also does not provide enough detail to determine whether all participants had the same duration of observation. The counts alone do not establish causation or quantify comparative risk.
12. What the Result Does, and Does Not, Mean
The record describes a Phase IV study of agalsidase beta in patients with cardiac Fabry disease and specifies a primary echocardiographic outcome: percent change from baseline to Week 156 in interventricular septum and left ventricular posterior wall thickness. It also describes a treatment schedule and reports selected adverse-event counts. These details explain what the study was intended to assess and what safety information the registry lists.
The record does not report the numerical primary endpoint result, its 95% confidence interval, or a p-value. It therefore does not show the size, direction, or precision of any change in wall thickness. Secondary outcome descriptions are present, but numerical results are not reported in the registry record for this analysis. The presence of an endpoint description is not itself evidence of a particular outcome.
The single-group, non-randomized design means that any measured change would be a within-group observation rather than a randomized treatment-versus-control contrast. In general, a before-and-after change cannot by itself distinguish the intervention’s contribution from other influences over time. The open-label design and the absence of a control group also limit the ability to make comparative inferences.
The enrollment of 6 participants makes the study’s scale clear, but the registry does not report how many contributed endpoint measurements at Week 156. It does not give the analysis model details, missing-data approach, or definition of EEP. Accordingly, the available information does not support a complete assessment of the endpoint analysis or its precision.
The safety counts are descriptive. The record reports 1 participant affected by a serious adverse event among 6 at risk, 6 affected by other adverse events among 6 at risk, and a serious adverse event term of large intestine carcinoma at 16.7%. It does not report a death count or provide a control group for comparison. These entries should not be treated as proof that an event was caused by treatment or as a comparative safety estimate.
In general, a trial result is most interpretable when the numerical effect, uncertainty, analysis population, and methods are available together. Those elements are not all reported in the registry record. The study’s design and endpoint can be described, but the primary outcome itself cannot be interpreted numerically from the available record.
13. Why This Trial Matters Statistically
This study raises several useful statistical issues for reading clinical trial records. It has a clearly identified continuous primary endpoint and a defined follow-up time: percent change from baseline in echocardiographic wall thickness at Week 156. It also states that the result was intended to be summarized as a least-squares mean with a 95% confidence interval. Yet the numerical estimate and interval are not reported in the registry record. This distinction illustrates why knowing an endpoint and its intended summary is not the same as having the result needed to assess its size and precision.
The design also makes the estimand important. The study is described as single-group and non-randomized, with no comparator arm. A change from baseline may describe the trajectory among participants, but it is not a randomized estimate of the difference attributable to treatment. Clear separation of within-group change from comparative treatment effect is essential when interpreting non-randomized evidence.
Enrollment was 6. In general, a small study can be informative about feasibility and can document measurements and safety events, but its estimates may be imprecise and sensitive to individual observations. The record does not provide the primary estimate or confidence limits needed to judge precision in this case. Nor does it define the EEP analysis population or report the number contributing Week 156 data.
The entry also lists 7 outcome measures but 0 analyses. Without results and details of multiplicity, missing-data handling, and model specification, it is not possible to evaluate how the outcomes were analyzed or how uncertainty was managed. The planning illustrations described in the record are not a replacement for the original design rationale or for observed outcome results. Together, these features make transparent reporting of analysis populations, methods, estimates, and uncertainty especially important for interpretation.
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 principal limitation for interpreting the primary outcome is that the registry record does not report its numerical estimate or 95% confidence interval. Although the endpoint and analysis parameter are named, there is no result from which to assess the direction, magnitude, or precision of change in interventricular septum and left ventricular posterior wall thickness.
The study enrolled 6 participants and used a single-group, non-randomized design without a control arm. Any within-group change cannot be separated from other influences over time by a randomized comparison. The record does not report the number of participants with Week 156 echocardiograms, participant-level follow-up, or treatment completion, so the analyzed group and completeness of follow-up cannot be determined.
Other analysis details are also absent. The primary population is identified as EEP but not defined. The statistical model, measurement and adjudication procedures, missing-data methods, multiplicity approach, and sensitivity analyses are not reported in the registry record. The outcome list includes secondary measures, but their numerical results are not available in the registry record described.
The safety record gives participant counts and a serious adverse event term, but does not provide event timing, duration, outcome, causality assessment, or a death count. Without a control group, the reported counts are descriptive and cannot serve as comparative safety estimates. The planning assumptions described for sample-size illustrations are not the trial’s documented design rationale, which is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Safety and Efficacy Study of Fabrazyme® Replacement Therapy in Patients With Cardiac Fabry Disease — NCT00140621.
- Registry record last updated 2015-05-12; status last verified 2015-04.
- Results first posted 2015-04-15.
- 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.
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18. Record Summary
This completed Phase IV study was a multicenter, open-label, non-randomized, single-group study of agalsidase beta in patients with cardiac Fabry disease. Enrollment was 6. Treatment was described as 1 milligram per kilogram by intravenous infusion once every 2 weeks for up to 156 weeks, after a baseline period of 4 weeks or less.
The primary endpoint was percent change from baseline to Week 156 in interventricular septum and left ventricular posterior wall thickness assessed by echocardiogram. The record specifies a least-squares mean and 95% confidence interval, but the numerical result and interval are not reported in the registry record. It lists 7 outcome measures and 0 analyses.
The record reports 1 participant affected by a serious adverse event among 6 at risk, 6 affected by other adverse events among 6 at risk, and large intestine carcinoma at 16.7% among the top serious adverse event terms. A death count is not reported in the registry record.