Safety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease (NCT00864851), a randomized phase 3 study. The primary outcome is Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI).

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, parallel-group, open-label study of Replagal dosing regimens in adults with Fabry disease. The registry identifies Shire as the sponsor and records the study as completed. The recorded start date is 2008-12-29, the primary completion date is 2012-06-01, and enrollment is 44.

Participants were assigned to one of three groups: Replagal 0.2 mg/kg intravenously every other week, Replagal 0.2 mg/kg intravenously weekly, or Replagal 0.4 mg/kg intravenously weekly. Each arm description specifies a 52-week regimen. Masking is listed as none, so the study is described as open-label rather than blinded. The registry record does not report the method used to generate or conceal the random allocation.

The primary outcome was change from baseline to Month 12 (Week 53) in left ventricular mass indexed to height. The primary endpoint population is described as randomized patients who received at least 1 complete or partial dose. The registry also lists changes in exercise capacity, walking distance, heart-failure questionnaire score, functional class, plasma GB3, kidney-related measures, and safety evaluation as secondary outcomes.

The primary result includes arm-level means and standard deviations for all three regimens. An inferential comparison is posted for weekly 0.2 mg/kg versus every-other-week 0.2 mg/kg. A comparison estimate for the 0.4 mg/kg weekly regimen is not reported in the registry record. Details of the original sample-size justification, allocation procedures, and 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial 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.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI), measured over Baseline, Month 12 (Week 53).

The primary endpoint is change from baseline to Month 12 (Week 53) in left ventricular mass indexed to height, measured in g/m^2.7. The registry states that left ventricular mass was measured through echocardiography and that the endpoint is expressed as a mean with standard deviation. The primary population is the ITT population defined in the record as all randomized patients who received at least 1 complete or partial dose of Replagal.

In general, a change score expresses how a measured quantity differs at follow-up from its baseline value. An indexed measure expresses a quantity in relation to another characteristic; the exact calculation details for this endpoint are not reported in the registry record. The registry's trial purpose and title frame the study around Replagal dosing and cardiac function, making a cardiac measure relevant to the stated question.

The reported endpoint values describe average changes within each arm. They do not by themselves establish that one regimen differs from another. That question requires a between-arm estimate, interpreted with its uncertainty and with attention to the size and composition of the analysis groups. The posted comparison estimate addresses the two 0.2 mg/kg schedules; an equivalent estimate for the 0.4 mg/kg weekly arm is not reported in the registry record.

7. Results Posted in the Registry

• Replagal 0.2 mg/kg, IV, Weekly: mean 0.50 versus 3.20 on control; difference -2.70 (95% CI -12.36 to 6.96), standardized effect d = -0.19; z-test p = 0.584.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline to Month 12 in Maximal Oxygen Consumption (VO2 Max) at Peak Exercise

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Replagal 0.2 mg/kg, IV, Weekly: mean -0.30 versus -2.00 on control; difference 1.70 (95% CI -1.25 to 4.65), standardized effect d = 0.41; z-test p = 0.258.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Replagal 0.2 mg/kg, IV, Weekly and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline to Month 12 in Distance Walked in 6-Minute Walk Test (6MWT)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Replagal 0.2 mg/kg, IV, Weekly: mean 37.90 versus -10.40 on control; difference 48.30 (95% CI -6.75 to 103.35), standardized effect d = 0.61; z-test p = 0.085.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Replagal 0.2 mg/kg, IV, Weekly and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline to Month 12 in the Minnesota Living With Heart Failure Questionnaire (MLHF-Q) Summary Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Replagal 0.2 mg/kg, IV, Weekly: mean 2.10 versus -3.10 on control; difference 5.20 (95% CI -4.44 to 14.84), standardized effect d = 0.36; z-test p = 0.290.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Replagal 0.2 mg/kg, IV, Weekly and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists a range of secondary questions that complement the primary cardiac structural measure. These include maximal oxygen consumption at peak exercise, distance walked in the 6-minute walk test, the Minnesota Living With Heart Failure Questionnaire summary score, NYHA functional class, plasma GB3, estimated glomerular filtration rate, urinary albumin/creatinine ratio, and safety evaluation. Together, these outcomes cover exercise performance, reported health status, functional classification, laboratory measures, kidney-related measures, and safety.

The posted numerical change summaries for exercise capacity, walking distance, and questionnaire score show that the direction and scale of observed changes are not uniform across measures or arms. The primary endpoint addresses a different aspect of the study question, so secondary measures can provide context but do not replace the primary comparison. None of the secondary results supplies a direct confirmation of the primary contrast simply by moving in a favorable or unfavorable direction.

The registry record does not list reported inferential analyses for these secondary outcomes. The posted comparisons are unadjusted summaries and should be treated as exploratory descriptions rather than as a coordinated set of definitive tests. In general, examining many outcomes raises the chance that some apparent differences will occur by chance, particularly when no adjustment strategy or hierarchy among outcomes is reported. The registry record does not report such a multiplicity strategy.

Different outcomes can also have different scales, measurement properties, participant counts, and degrees of variability. Their estimates should not be compared as though the numerical units were interchangeable. The secondary outcomes may help describe what was measured, but the lack of a reported analysis plan, inferential results across the full set, and multiplicity handling limits the strength of conclusions that can be drawn from their pattern.

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

• Change From Baseline to Month 12 in Maximal Oxygen Consumption (VO2 Max) at Peak Exercise
• Change From Baseline to Month 12 in Distance Walked in 6-Minute Walk Test (6MWT)
• Change From Baseline to Month 12 in the Minnesota Living With Heart Failure Questionnaire (MLHF-Q) Summary Score
• Change From Baseline to Month 12 in New York Heart Association (NYHA) Functional Class
• Change From Baseline to Month 12 in Plasma Globotriaosylceramide (GB3)
• Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)
• Change From Baseline to Month 12 in Urinary Albumin/Creatinine (A/Cr) Ratio
• Safety Evaluation

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean change represent?

The primary outcome is continuous: it can take a range of measured values rather than placing each participant in a category. For a continuous outcome, the arm-level mean is the average change among the participants contributing data to that summary. The registry reports a mean and standard deviation for each dosing arm. The mean gives a central summary of the changes; the standard deviation describes how spread out individual changes are around that mean.

The primary endpoint is a change from baseline to Month 12 (Week 53). A change measure uses each participant's baseline and follow-up values to express movement over the study period. The registry says left ventricular mass was measured through echocardiography. It does not report further measurement details, such as reading procedures or how a participant's value was handled if a measurement was unavailable.

How should the between-arm estimate be read?

The posted estimate compares the mean change in the weekly 0.2 mg/kg arm with the mean change in the every-other-week 0.2 mg/kg arm. The mean difference is -2.7 g/m^2.7. The sign indicates the direction of the contrast as posted, while the interval communicates the uncertainty around its estimated size. The registry does not post a corresponding inferential comparison for the 0.4 mg/kg weekly arm.

In general, a confidence interval is a range of values compatible with the observed data under the assumptions of the method used. A confidence interval that includes zero for a difference does not establish that the groups are identical. Rather, it indicates that the data do not sharply distinguish a zero difference from other values within the interval. The posted 95% confidence interval ranges from -12.36 to 6.959 g/m^2.7, so its range includes zero and values in both directions.

What does the p-value tell the reader?

The unadjusted p-value for the posted primary comparison is 0.584. In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of a difference. The registry record does not report the full model or test specification used for a sponsor analysis. The displayed comparison is a simple, unadjusted comparison based on posted summary statistics.

Unadjusted means that the p-value is not described as corrected for considering multiple comparisons. When many outcomes or contrasts are examined, the chance of obtaining a small p-value by chance can increase. The registry record does not report a multiplicity strategy. The single posted primary contrast should therefore be distinguished from a complete prespecified testing strategy, which is not reported in the registry record.

Why does variation matter?

For continuous outcomes, differences in group means need to be read alongside within-group variation and sample sizes. When observations vary widely, a mean difference is estimated less precisely than it would be if observations were more tightly clustered, all else equal. The reported standard deviations are 12.5, 15.8, and 11.8 g/m^2.7 for the every-other-week 0.2 mg/kg, weekly 0.2 mg/kg, and weekly 0.4 mg/kg arms, respectively. The groups contributing to the primary summaries contain 15, 18, and 5 participants.

In general, standard error describes the sampling uncertainty of an estimate, whereas standard deviation describes variability among observations. The registry record does not report a sponsor model's standard errors or detailed modeling choices. It does report an unadjusted comparison interval and p-value, which convey uncertainty for the two-arm contrast.

What is not documented about the analysis?

The primary population is defined as randomized patients who received at least 1 complete or partial dose of Replagal. The registry record does not report details of the planned statistical analysis, the approach to missing follow-up data, whether baseline covariates were included, or whether any interim analyses were planned. The registry lists no reported analyses in its analysis listings. These omissions mean that readers cannot reconstruct the complete protocol-based analysis from the registry record alone.

General statistical interpretation also depends on whether the analysis population and methods match the study question. Randomization supports comparisons between assigned groups, but open-label conduct can affect behavior, reporting, or measurement processes in ways that depend on the outcome. The registry does not report whether or how such possibilities were addressed. The posted summaries should consequently be interpreted as descriptive arm results plus an unadjusted estimate for one contrast, rather than as a fully documented analysis plan and results package.

11. Confidence Intervals and Precision

The main precision information for the primary comparison is the mean difference of -2.7 g/m^2.7 and its 95% confidence interval, from -12.36 to 6.959 g/m^2.7. The interval extends across zero, so the estimate does not pin down a single direction of difference. It includes the possibility of a negative difference, no difference, and a positive difference under the interval's statistical assumptions.

In general, a confidence interval gives a range of estimates that are reasonably compatible with the data and method. It is not a range containing a known proportion of individual participant outcomes. A narrower interval would convey greater precision, while a wider interval indicates greater uncertainty about the size of the between-group difference. The posted interval remains broad enough to include meaningfully different estimates in both directions; the registry record does not define a threshold for a clinically important difference, so the interval cannot be classified against such a threshold.

The primary arm summaries are based on 15 participants in the every-other-week 0.2 mg/kg group, 18 in the weekly 0.2 mg/kg group, and 5 in the weekly 0.4 mg/kg group. Smaller groups generally offer less information for estimating means and differences, especially when participant outcomes vary. The registry record gives standard deviations for the groups but does not post a confidence interval for the 0.4 mg/kg arm's mean or an inferential contrast involving that arm.

The unadjusted p-value of 0.584 is consistent with substantial uncertainty in the posted two-arm contrast; it should not be treated as a measure of precision by itself. The interval is the more direct description of the range of difference estimates compatible with the reported comparison. Missing-data handling, model assumptions, and the analysis plan are not reported in the registry record, so they cannot be assessed as contributors to the precision estimate.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are calculated for a two-arm comparison using the observed effect as a reference, then considering the stated fractions of that effect. They are not the original trial enrollment target or the number actually analyzed in each arm. The original sample-size justification and assumptions are not reported in the registry record.

The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For these continuous outcomes, figures refer to participants per arm; the note about total event counts applies to time-to-event tables, not to these continuous-outcome planning figures.

In plain language, 80% power describes a design that would detect the specified effect in 80% of repeated studies under the planning assumptions, if that effect and the other assumptions were true. The 90% column uses a higher probability of detecting that same specified effect, and therefore calls for more participants under otherwise comparable assumptions. Smaller effects are harder to distinguish from background variation, so the planning illustrations require more participants as the target effect becomes smaller.

For the primary comparison, the observed-effect planning row lists 447 participants per arm for 80% power and 599 participants per arm for 90% power. The rows for 75% and 50% of the observed effect list larger requirements. These are illustrative calculations based on the observed comparison, not the trial's own design rationale. This is not observed power: the figures describe hypothetical future planning under stated assumptions, not the probability that the completed study detected an effect.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -2.700; pooled standard deviation σ = 14.404.
2. n = 2 × (1.96 + 0.842)² × 14.404² / -2.700² = 446.7, rounded up to 447 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -2.7                      # observed difference in means
sigma <- 14.4036061792782                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(864851)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 447 (80% power), 599 (90% power)
 75% of observed effect: n per arm = 795 (80% power), 1,064 (90% power)
 50% of observed effect: n per arm = 1,787 (80% power), 2,393 (90% power)
power.t.test: 447.7 
Simulated power at n = 447 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and several secondary outcomes, but it does not report how testing across outcomes or treatment contrasts was controlled. A multiplicity plan can specify which comparisons are confirmatory, how tests are ordered, or how significance thresholds are adjusted when several questions are examined. Without such information, the posted unadjusted p-values should not be interpreted as though they necessarily account for the full set of outcomes and arms.

The primary comparison has an unadjusted p-value of 0.584. The registry record does not report a multiplicity-adjusted result, a prespecified testing hierarchy, or an analysis plan explaining whether the comparison was the sole confirmatory contrast. It also does not report inferential comparisons involving the 0.4 mg/kg weekly arm. The posted arm means alone cannot fill that gap.

The record defines the primary population as randomized patients who received at least 1 complete or partial dose. This definition is useful, but it is not a complete account of all analysis populations. The registry record does not report a separate safety population definition, a per-protocol population, or how participants with missing endpoint measurements were treated. It does not report whether missing values were imputed, whether analyses used only available measurements, or whether sensitivity analyses assessed the impact of missing data.

For secondary outcomes, participant counts differ from the primary endpoint groups in some summaries. The record does not explain why the counts differ or whether differences reflect unavailable measurements, eligibility for a particular assessment, or another reason. No cause should be inferred from the counts alone. Details about endpoint-specific analysis populations and missing-data handling are not reported in the registry record.

The absence of these details limits assessment of the robustness of the results and how closely the posted summaries correspond to any planned protocol analysis. It does not, by itself, demonstrate that a particular method was or was not used. The registry record does not report interim analysis plans, stopping rules, or the original statistical analysis plan.

15. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sinus bradycardia (20.0%), facial paresis (20.0%), musculoskeletal chest pain (5.3%), gouty arthritis (5.3%), atrioventricular block complete (5.3%).

The registry reports serious adverse events for each regimen and overall. Serious adverse events affected 8 of 20 participants at risk in the every-other-week 0.2 mg/kg group, 5 of 19 in the weekly 0.2 mg/kg group, and 2 of 5 in the weekly 0.4 mg/kg group. Overall, 15 of 44 participants at risk were reported with serious adverse events. These are counts of participants with at least one serious adverse event as represented in the registry data; they do not give the number of separate serious-event episodes.

The record also reports other, non-serious adverse events affecting 19 of 20, 17 of 19, and 5 of 5 participants in the respective groups, with 41 of 44 overall. The listed serious terms include sinus bradycardia and facial paresis, each shown as 20.0%, along with musculoskeletal chest pain, gouty arthritis, complete atrioventricular block, and nausea, each shown as 5.3%. The registry record does not specify in the posted summary the denominator used for each listed term.

These figures describe events recorded during the study and are not adjusted comparisons between regimens. The number of participants at risk is small, particularly in the 0.4 mg/kg weekly group, and the registry does not provide comparative safety analyses or event timing in the posted details. Death counts are not reported in the registry record.

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

The results describe changes in left ventricular mass indexed to height and other outcomes among participants assigned to three Replagal regimens. For the two 0.2 mg/kg schedules, the posted mean difference is -2.7 g/m^2.7, with a 95% confidence interval from -12.36 to 6.959 and an unadjusted p-value of 0.584. The interval includes zero and values on either side, so the estimate is not precise enough to establish a clear direction of difference between those groups.

The third regimen has an arm-level mean change, but no inferential comparison with the other groups is reported in the registry record. Its result should therefore not be interpreted as evidence that the 0.4 mg/kg weekly regimen is better or worse than either 0.2 mg/kg schedule. Comparing arm means without a corresponding estimate and uncertainty can overstate what the data establish, especially with only 5 participants contributing to that primary arm summary.

In general, a non-significant result is not proof that two treatments are equivalent. Equivalence or non-inferiority requires an appropriate prespecified margin and analysis; such a margin and analysis are not reported in the registry record. Likewise, a numerical difference in a group mean does not by itself establish that the difference is important to patients or clinically meaningful. The record does not report a threshold for clinical importance.

The results also do not establish what would happen outside the studied population or beyond the study period. The registry describes adults with Fabry disease and cardiomyopathy and regimens specified for 52 weeks. The posted summaries should be read as evidence about the measured outcomes in this study, with the uncertainty and reporting gaps described, rather than as broad conclusions about all people with Fabry disease or all possible dosing schedules.

17. Why This Trial Matters Statistically

This trial raises several statistical issues common to randomized studies with multiple arms and a modest enrollment. The three-arm design allows several dosing regimens to be described, but an arm-level mean is not the same as a tested contrast. The registry provides an inferential estimate for only the comparison between the two 0.2 mg/kg schedules. Readers need to keep that distinction clear when viewing all three sets of primary outcome summaries.

The primary contrast is imprecise: its confidence interval covers zero and a range of estimates in either direction. This makes the confidence interval more informative than a simple focus on whether a p-value crosses a conventional threshold. The groups contributing to the primary endpoint are small, especially the weekly 0.4 mg/kg group, which illustrates why the amount of information matters when interpreting group averages and comparisons.

The trial also lists a broad set of secondary outcomes. Such breadth can add useful descriptive context, but it creates a need for a clear analysis hierarchy and multiplicity strategy if the results are intended to support confirmatory claims across outcomes. Those procedures are not reported in the registry record. The secondary findings therefore require particular caution and should not be treated as independent confirmation of the primary comparison.

Finally, this record distinguishes between results that are available and methods that are not documented. It identifies the primary population and the endpoint, but does not report important details about missing data, the original sample-size justification, interim analyses, or the complete statistical plan. That distinction is central to responsible interpretation: a numerical result can be described precisely while the design and analysis context remains incomplete.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The trial enrolled 44 participants, and the primary endpoint summaries include 15 participants in the every-other-week 0.2 mg/kg arm, 18 in the weekly 0.2 mg/kg arm, and 5 in the weekly 0.4 mg/kg arm. This limits the amount of information available, particularly for interpreting the third arm. The registry record does not report a comparison estimate involving that arm, so its mean change cannot be used to make a well-supported between-regimen inference.

The study was open-label, with masking listed as none. The registry record does not report whether outcome assessment was blinded or what procedures were used to limit possible effects of open-label conduct on measurement or reporting. This is relevant context, but the registry information does not establish that such effects occurred.

Participant counts differ across some outcome summaries. The registry does not explain the reasons for those differences or describe how missing endpoint data were handled. It also does not report sensitivity analyses for missing data. As a result, the impact of incomplete outcome measurement cannot be assessed from the registry record.

The posted primary comparison is unadjusted, and a multiplicity plan is not reported. The record also does not provide the original sample-size justification, details of the allocation procedure, interim analysis plans, a complete analysis plan, or a reported inferential analysis for every arm and endpoint. These are reporting limitations; they do not establish that the corresponding procedures were absent from the study itself.

The registry describes outcomes at Month 12 (Week 53) and dosing regimens for 52 weeks. Longer-term outcomes are not reported in the record. The available summaries therefore do not describe persistence of changes beyond the recorded follow-up or support conclusions about outcomes not included among the posted measures.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease — NCT00864851.
• Registry record last updated 2021-06-09; status last verified 2021-05.
• Results first posted 2014-06-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT00864851 is a completed, randomized, open-label, parallel-group Phase 3 study of Replagal dosing regimens in adults with Fabry disease. The registry records enrollment of 44 and specifies three regimens: 0.2 mg/kg intravenously every other week, 0.2 mg/kg intravenously weekly, and 0.4 mg/kg intravenously weekly, each described for 52 weeks.

The primary endpoint was change from baseline to Month 12 (Week 53) in left ventricular mass indexed to height, measured by echocardiography. The posted comparison of the two 0.2 mg/kg schedules has a mean difference of -2.7 g/m^2.7, a 95% confidence interval from -12.36 to 6.959, and an unadjusted p-value of 0.584. A comparison estimate involving the 0.4 mg/kg weekly arm is not reported in the registry record.

The record lists several secondary outcomes and reports adverse-event counts. It does not report the original sample-size justification, complete statistical analysis plan, multiplicity procedures, or missing-data methods. Those omissions limit how fully the study's analysis can be reconstructed from the registry record.