Efficacy and Safety Study of Velaglucerase Alfa in Children and Adolescents With Type 3 Gaucher Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of Velaglucerase Alfa in Children and Adolescents With Type 3 Gaucher Disease (NCT01685216), a na phase 1, phase 2 study. The primary outcome is Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration.

2. Clinical Question

The registry describes the study as investigating the safety and effectiveness of velaglucerase alfa in type 3 Gaucher disease. Its primary outcome is a change from baseline in hemoglobin concentration, measured in g/dL. The registry defines a positive change as an increase. Baseline is a modified value calculated from measurements at screening, baseline, and Week 1/Day 1.

Because the study has no separate control group, its primary question is about change over time within the treated group, not a difference between treatment and control. The registry record does not report the numerical primary outcome result, so the magnitude and precision of the observed change cannot be described from the posted record.

3. Trial Design

This was a multicenter, open-label study registered in Phase 1 and Phase 2. It is classified as a single-group study with allocation recorded as not applicable and masking recorded as none. The registry reports enrollment of 7 participants and a completed study status.

The recorded intervention was velaglucerase alfa, administered by intravenous infusion at 60 U/kg every other week for 1 year. The registry dates the study start as 2012-09-14 and primary completion as 2015-03-15. Those dates describe the record’s study timeline; further details about recruitment, individual follow-up, or the timing of each participant’s last assessment are not reported in the registry record.

In a single-group design, outcomes can be described over time in the treated participants, but there is no concurrent untreated or alternative-treatment group to provide a direct comparison. An open-label study also means masking was not used, as recorded in the registry. The record does not provide further details about procedures intended to limit measurement or reporting bias.

The primary outcome was change in hemoglobin concentration from baseline to 12 months, specified as Week 53 or the end of the study. Secondary outcomes included change in platelet count; percent changes in normalized liver and spleen volume measured using magnetic resonance imaging; abnormal neurological status during the study; treatment-emergent adverse events; and development of anti-velaglucerase alfa antibodies. A seventh outcome measure is indicated by the record’s count, but another outcome description is not reported in the registry record.

The registry record does not report a sample-size justification, randomization procedure, or a statistical analysis plan. The study’s enrollment and single-group structure should therefore be read as descriptive features, not as evidence of a particular design rationale or planned precision.

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: The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).

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: The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration, measured over Baseline, Week 53 or end of study.

The primary endpoint is change from baseline to 12 months in hemoglobin concentration, reported in g/dL. Hemoglobin concentration was measured through a hematology panel or separately when that panel was not scheduled, with samples measured by a central laboratory. The registry defines baseline as the modified baseline hemoglobin concentration: the average of values from screening, baseline, and Week 1/Day 1. The endpoint timeframe is baseline to Week 53 or the end of the study.

A change score describes how a measured characteristic differs between a participant’s starting value and a later assessment. The registry states that a positive change represents an increase in hemoglobin concentration. The primary outcome is defined as a mean, with standard deviation as its dispersion measure. In general, the mean summarizes the group’s average change, while the standard deviation describes how much participant-level changes vary around that average.

Hemoglobin is the specified primary measure for this study, but the registry record does not provide the numerical change, its standard deviation, or a confidence interval. The rationale for selecting this endpoint and the clinical interpretation intended for a particular size of change are not reported in the registry record. Accordingly, the endpoint definition can be described, but the posted record does not support a conclusion about the size or precision of the primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

General statistical explanation: a mean change is the average of individual changes between a defined starting assessment and a later assessment. It provides a measure of the group’s central tendency, but it does not show whether every participant changed in the same direction or by a similar amount. The standard deviation describes the spread of individual values around the mean. A mean and standard deviation together give information about average change and variability, but they do not by themselves show the precision of the estimated mean.

For this study, the registry specifies mean change in hemoglobin concentration as the primary outcome and standard deviation as the dispersion measure. It defines a positive change as an increase and specifies the modified baseline calculation and follow-up timeframe. The numerical mean and standard deviation are not reported in the registry record, so those summaries cannot be interpreted for this trial from the registered results.

How should baseline-to-follow-up change be read?

General statistical explanation: a change score compares a measurement at follow-up with a baseline measurement. In a study where the same participants are assessed at both times, the observations are related rather than independent. A statistical analysis may account for that relationship, but the specific method used is not reported in the registry record. The endpoint description alone does not establish which model or test, if any, was used.

The baseline definition matters because the result depends on which starting value is used. Here, baseline is defined as the average of values from screening, baseline, and Week 1/Day 1. The endpoint timeframe is Week 53 or the end of the study. The registry does not provide individual measurements, the number of participants with both baseline and follow-up data, or the analysis method. It is therefore not possible to independently reconstruct the mean change from the record.

What would a confidence interval add?

General statistical explanation: a confidence interval is a range of values generated by a statistical procedure to express uncertainty around an estimate. A narrower interval generally indicates greater precision than a wider interval, under the assumptions of the analysis. A confidence interval is not a guarantee that the true value lies within that particular interval, and it does not replace interpretation of the study design or data quality.

No confidence interval for the primary outcome is reported in the registry record. Without a point estimate and an interval, neither the estimated change nor its statistical precision can be assessed from the posted primary results. A p-value is also not reported for this outcome; no significance claim can be made from the endpoint definition alone.

Why does the single-group design matter?

General statistical explanation: a comparison group can help distinguish changes that occur under an intervention from changes that might also occur over time without it. In a single-group study, a baseline-to-follow-up change is observed in participants who receive the intervention, but that change is not a randomized treatment contrast. Factors such as the passage of time, measurement conditions, or participant characteristics could also be relevant to interpreting change. The registry does not describe analyses intended to address such factors.

This study is recorded as single-group, open-label, with no masking and allocation not applicable. The design therefore does not support a direct randomized comparison with another intervention or a control. This does not erase the descriptive value of repeated measurements, but it limits the interpretation of any change as an effect attributable to treatment. In this case, the primary numerical outcome is also not posted, so even a descriptive estimate is unavailable in the registry record.

What is the role of the analysis population?

The registry defines the Intent-to-Treat population as all participants who received at least 1 study drug infusion, full or partial. This definition identifies who is intended to be included in the primary analysis population. It does not state how many participants had an observed primary endpoint, how missing follow-up measurements were handled, or whether any additional analysis populations were used. Those details are not reported in the registry record.

Enrollment was 7, while the posted safety summaries list 6 participants at risk for serious and other adverse events. These figures refer to different reported items, and the registry record does not explain the difference. It would not be appropriate to assume a reason for the discrepancy or to treat the safety denominators as the primary outcome sample size.

How should the planning illustrations be interpreted?

General statistical explanation: sample-size calculations estimate how many participants would be needed under specified assumptions to detect a chosen effect with a chosen statistical procedure and power. A planning calculation is not a measure of what the completed study actually detected, and it cannot substitute for an observed estimate and its uncertainty. Observed power is not an appropriate description of a completed study’s result.

The stated assumptions for the planning illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect described as a stated fraction of an observed effect. Those assumptions do not match this trial’s single-group registered design. The resulting illustrations, if considered, are hypothetical planning scenarios rather than observed power or evidence about the primary endpoint. The numerical inputs and any trial-specific sample-size justification are not reported in the registry record.

What is and is not specified about statistical methods?

The registry identifies outcome measures and the primary endpoint’s summary type, but it reports no posted analyses. A statistical analysis plan, hypothesis tests, adjustment methods, confidence intervals, and handling of multiplicity are not reported in the registry record. This absence means the methods behind numerical estimates cannot be evaluated from the registered record; it does not establish that no analyses were performed outside the record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Velaglucerase Alfa")
n   <- c(6)
m   <- c(2.15)
sp  <- c(1.213)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Velaglucerase Alfa  6  2.150  1.213  0.877  3.423

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary outcomes concerning platelet count, normalized liver volume, normalized spleen volume, neurological status, treatment-emergent adverse events, and anti-velaglucerase alfa antibodies. It records 7 outcome measures, while the outcome descriptions do not provide a further measure beyond the primary and the listed secondary outcomes. Numerical results for these outcomes and any analysis plan are not reported in the registry record.

When a study assesses several outcomes, multiplicity can arise if many statistical tests are conducted. General statistical explanation: the more tests considered, the greater the opportunity for at least one apparently unusual result by chance, depending on the testing plan. Researchers may specify a hierarchy of outcomes or an adjustment approach. The registry record does not report whether a multiplicity strategy was planned or used, so no correction or prioritization should be assumed.

The primary analysis population is defined as all participants receiving at least 1 full or partial study drug infusion. The number with available primary endpoint data and the analysis population for each secondary outcome are not reported in the registry record. The record also does not state whether missing data occurred, why any data might be missing, or how missing measurements were handled. No imputation or other missing-data method should be inferred.

Although the primary outcome description specifies a mean and standard deviation, the registry does not report a statistical analysis plan or posted analyses. It is therefore not possible to determine from the registry whether results were adjusted, which tests were used, or how any departures from the planned assessment schedule were handled.

12. 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: inguinal hernia (16.7%).

The registry’s serious adverse event summary lists 6 participants at risk and 1 participant affected in the velaglucerase alfa group. Its summary for other adverse events lists 6 participants at risk and 6 affected. These are counts from the posted safety record; they should not be interpreted as a comparison with another group because the study had no separate comparator.

The registry lists inguinal hernia as a top serious term, with 16.7%. The record does not provide further details in this summary about event timing, seriousness criteria, relationship to treatment, or whether the term represents one or more events. Those details are not reported in the registry record.

The safety denominators are 6, whereas total enrollment is 7. The registry record does not explain the difference, so no reason should be inferred. The deaths field does not contain a numerical value. Deaths are not reported in the registry record; an unpopulated field is not evidence that none occurred. These summaries are limited to the information recorded and do not establish comparative safety.

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

The registry establishes that a completed, multicenter, open-label, single-group study enrolled 7 children and adolescents with type 3 Gaucher disease and evaluated velaglucerase alfa. It defines a primary outcome based on mean change in hemoglobin concentration from a specified baseline to Week 53 or the end of the study. It also identifies several secondary outcome areas and reports selected safety counts.

The registry record does not report the numerical primary outcome result. It therefore does not show how large the mean hemoglobin change was, how variable participant changes were, or how precisely the mean was estimated. Without these results, the direction and size of the observed primary outcome cannot be stated. The record also does not report numerical results for the listed secondary outcomes.

The single-group design allows description of outcomes among participants receiving the intervention, but does not provide a randomized comparison with another treatment or a control group. Any observed change in such a design would not, on its own, isolate the contribution of treatment from other explanations. In this record, the absence of the primary estimate further limits interpretation.

The safety summaries report affected-participant counts and a serious adverse event term, but provide no comparator and do not give enough detail to characterize timing or attribution. The registry does not report a numerical death count. These limitations mean the posted safety information should be read as a record of selected reported counts, not as a comparative estimate or a complete account of safety.

In short, the registry record describes the study question, design, outcome definitions, and some safety information. It does not provide the numerical efficacy results required to evaluate the primary endpoint or its precision. It also does not support a conclusion about comparative effects.

14. Why This Trial Matters Statistically

This study illustrates why design and result availability matter together. The registry specifies a clinically oriented measurement—change in hemoglobin concentration—and defines how baseline and follow-up are framed. Those definitions make the intended endpoint understandable. But without the numerical estimate and its variability, the outcome cannot be assessed quantitatively.

The single-group structure is also important. A within-participant change can be useful as a description of what happened during follow-up, but it is not the same as a randomized contrast. The distinction is essential when interpreting results: a change over time and a treatment effect relative to a comparator answer different questions. Here, the registry record reports no primary estimate, so neither the descriptive change nor a comparative effect can be evaluated from the posted results.

The record also shows how denominator definitions affect interpretation. Enrollment is 7, the primary population is defined by receipt of at least 1 infusion, and safety summaries list 6 participants at risk. Since the record does not reconcile these counts, interpreting the safety denominators as though they represented every enrolled participant would go beyond what is documented.

Finally, registered outcome definitions are not a substitute for a statistical analysis plan or completed numerical results. Multiplicity handling, missing-data methods, and inferential procedures are not reported in the registry record. Distinguishing what the record describes from what it leaves unspecified is necessary for a calibrated statistical reading.

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 study’s enrollment was 7, and the single-group design provides no concurrent control group. This limits direct comparison and makes it difficult to separate change over time from change associated with the intervention. The study was open-label, with masking recorded as none; further details about outcome-assessment safeguards are not reported in the registry record.

The primary endpoint is clearly defined, but its numerical result is not reported. The registry also does not report the number of participants with available Week 53 or end-of-study measurements, the primary outcome’s standard deviation, or a confidence interval. The primary population definition does not resolve these missing details.

The safety summaries list 6 participants at risk, compared with enrollment of 7, without explaining the difference. The deaths field contains no numerical value, and the registry record does not report a death count. Event-level details, including timing and attribution, are not reported in the registry record.

The registry identifies secondary outcomes but does not report numerical results or a multiplicity plan. It does not report missing-data methods, a statistical analysis plan, or a sample-size justification. These omissions restrict evaluation of outcome precision, analysis choices, and the rationale for the study’s enrollment. They should be treated as limitations of what the registry record documents, not as evidence that particular procedures were or were not performed outside the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of Velaglucerase Alfa in Children and Adolescents With Type 3 Gaucher Disease — NCT01685216.
• Registry record last updated 2021-06-11; status last verified 2021-05.
• Results first posted 2015-10-30.
• 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

NCT01685216 is a completed, multicenter, open-label, single-group study of velaglucerase alfa in children and adolescents with type 3 Gaucher disease. The registry reports enrollment of 7 participants and an intervention regimen of 60 U/kg by intravenous infusion every other week for 1 year. The recorded study start is 2012-09-14, and primary completion is 2015-03-15.

The primary outcome is mean change in hemoglobin concentration from baseline to Week 53 or the end of the study. The registry defines the baseline measure and identifies standard deviation as the dispersion measure, but does not report the numerical primary result. The primary population includes participants who received at least 1 full or partial infusion.

Safety summaries list 1 of 6 participants affected by serious adverse events and 6 of 6 affected by other adverse events. Inguinal hernia is listed as a top serious term at 16.7%. The registry record does not report a numerical death count, a statistical analysis plan, or numerical primary outcome results.