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 Study of the Effect of Aldurazyme® (Laronidase) Treatment on Lactation in Female Patients With Mucopolysaccharidosis I (MPS I) and Their Breastfed Infants (NCT00418821), a na phase 4 study. The primary outcome is Number of Lactating Women With Serum IgG Antibodies to Laronidase.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00418821 |
| Phase | Phase 4 |
| Condition | Mucopolysaccharidosis I, Hurler's Syndrome, Hurler-Scheie Syndrome |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genzyme, a Sanofi Company |
| Results posted | Yes |
2. Clinical Question
Population
Women with mucopolysaccharidosis I (MPS I) who were treated with laronidase and intended to breastfeed while receiving it, together with their breastfed infants. The registry lists Hurler's Syndrome, Hurler-Scheie Syndrome, and Scheie among the conditions.
Intervention
Laronidase, also identified in the study title as Aldurazyme®. The study concerned treatment of the mothers while they were breastfeeding.
Comparator
No separate comparator group is reported. The study is described as single-group, with allocation listed as NA and masking listed as none. The mother and infant groups in the adverse-event record are not a like-for-like control comparison.
Primary question
How many lactating women had serum IgG antibodies to laronidase during follow-up of up to 18 months? The broader study purpose also concerned whether laronidase was present in breast milk and the growth, development, and immunologic response of breastfed infants.
The registry describes a multicenter, multinational, open-label study. Its central clinical context is exposure to laronidase during lactation: mothers received treatment while intending to breastfeed, and the infants were breastfed during maternal treatment. The record identifies laronidase as the intervention but does not describe a treatment contrast against an untreated group or another therapy. It therefore sets out a descriptive question about treated mothers and their infants, rather than a randomized comparison of treatment strategies.
The primary endpoint focuses on maternal serum IgG antibodies to laronidase. It is distinct from the study's broader questions about drug presence in breast milk and infant outcomes. Although the registry lists 31 outcome measures, the result for the primary endpoint is not reported in the registry record. The record also does not report results for the broader questions in the study purpose. Accordingly, the clinical questions can be described, but the posted information does not establish what was observed for those questions.
3. Trial Design
This was a phase 4, open-label, single-group study of laronidase in women with MPS I who intended to breastfeed while receiving treatment, with their breastfed infants also included in the study description. The official title describes the study as multicenter and multinational. Allocation is listed as NA, and masking as none. Enrollment is reported as 2. The record lists the study status as terminated and gives a primary completion date of 2022-12-21. A reason for termination is not reported in the registry record.
The record's arm description identifies mothers treated with laronidase and infants who were breastfed while their mothers received laronidase. These are related study populations, not independent treatment and control groups. The registry explicitly flags that the study is not a randomized comparison and that its arms are not a like-for-like control comparison. Consequently, contrasts between mother and infant entries in the adverse-event record should not be interpreted as treatment effects.
The design information supports describing the study as an open-label, single-group investigation, but does not establish how participants were recruited, how measurements were scheduled beyond the primary endpoint's timeframe, or how long each participant contributed data. Those details are not reported in the registry record. Nor does the record state why the study was terminated or whether termination affected any particular outcome. Enrollment of 2 means the findings, if reported, would arise from a very limited set of observations; it does not by itself explain the study's design choices or the completeness of follow-up.
A sample-size justification, planned enrollment rationale, and detailed protocol are not reported in the registry record. The design should therefore be interpreted from the stated features alone, without inferring a planned comparison or assuming that the study was powered for a particular outcome.
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: Study was conducted to fulfill a post marketing commitment (PMC). Upon acknowledgement of closure of PMC by FDA, the study was terminated by the Sponsor.
Overall Study
| Stage | Laronidase |
|---|---|
| STARTED | 2 |
| COMPLETED | 1 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Laronidase |
|---|---|
| Fulfils one of the exclusion criteria | 1 |
Analysis population for the primary outcome, as defined in the registry: Mothers treated with laronidase who intended to breastfeed their infants while receiving laronidase.
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.
| Characteristic | Unit | Laronidase |
|---|---|---|
| Participants analysed | 2 | |
| Age, Customized: Newborns (0-27 days) | participants | 1 |
| Age, Customized: Adults (between 18 and 64 years) | participants | 1 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | — |
| Race (NIH/OMB): Asian | Participants | — |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | — |
| Race (NIH/OMB): Black or African American | Participants | — |
| Race (NIH/OMB): White | Participants | — |
| Race (NIH/OMB): More than one race | Participants | — |
| Race (NIH/OMB): Unknown or Not Reported | Participants | — |
6. Primary Endpoint
The registry lists the primary outcome as Number of Lactating Women With Serum IgG Antibodies to Laronidase, measured over Up to 18 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled “Number of Lactating Women With Serum IgG Antibodies to Laronidase.” Its unit is participants, its measurement type is a count of participants, and its timeframe is up to 18 months. The specified population is mothers treated with laronidase who intended to breastfeed while receiving it. The endpoint concerns whether women in that population had serum IgG antibodies to laronidase during the stated follow-up period.
As a participant count, the endpoint is a binary outcome at the individual level: each woman either meets the antibody outcome definition or does not. Reporting the number who meet the definition can describe how often the outcome was observed in the study population. It does not, by itself, explain the timing, persistence, or clinical consequences of an antibody finding. Those questions would require additional definitions and results, which are not reported in the registry record.
Antibody measurement is relevant to the study's stated interest in maternal and infant immunologic response during lactation. However, this endpoint is not a direct measure of laronidase concentration in breast milk, infant growth, infant development, or an infant immune outcome. The study purpose names those broader interests, but they should not be conflated with the stated primary endpoint.
The registry record does not report the observed primary endpoint count, an estimate of uncertainty, or a detailed outcome definition. Thus, the endpoint's purpose and measurement type can be described, but its result and precision cannot be assessed from the posted record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the primary endpoint and its timeframe, but does not report the observed number of lactating women with serum IgG antibodies to laronidase. It therefore supplies no primary-endpoint estimate to interpret. No confidence interval, statistical test, or other analysis result for that endpoint is reported in the registry record. The registry entries do not establish whether antibodies were observed, how frequently they occurred, or how precisely their frequency could be estimated.
Enrollment is reported as 2. That figure describes the study enrollment, not the number with a completed primary-endpoint assessment. The record does not state how many participants contributed data to the endpoint or whether follow-up was complete. It would therefore be inappropriate to treat enrollment as the endpoint denominator or to derive an event proportion from it.
The study is single-group, open-label, and not a randomized comparison. Its design can support description of outcomes in the enrolled study population if those outcomes are reported, but it does not offer a like-for-like control group for estimating what would have happened under a different treatment condition. The mother and infant group labels in the safety record represent different populations and do not create a treatment comparison. Any apparent difference between their entries would not establish a causal effect.
The posted adverse-event figures report, for each listed group, 1 participant at risk for other adverse events and 1 affected; the serious-event figures list 1 at risk and 0 affected in each group. Deaths are listed as 0 for both groups. These entries describe the safety information recorded for the mother and infant groups. They are not results for the primary antibody endpoint, and the registry record does not provide event terms for the other adverse events or identify their relationship to treatment.
The registry lists 31 outcome measures and 0 analyses. That means the record contains many listed measures but no analyses in the posted analysis listing; it does not reveal what analyses may have been planned or performed outside that listing. The primary result's absence, the limited enrollment, and the lack of a comparator all constrain interpretation. The record cannot establish the occurrence or absence of the broader outcomes named in the study purpose, including breast-milk presence of laronidase and infant growth, development, or immunologic response.
Any sample-size figures displayed as planning illustrations should be read as hypothetical design calculations, not as evidence of observed power or as a substitute for a reported result. The planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects framed as fractions of an observed effect. Those assumptions do not match the stated single-group design, and a planning illustration does not establish that the trial itself used that design or analysis.
9. Statistical Methods Explained
Interpretation begins with the study design. A randomized controlled comparison assigns participants to treatment conditions so that outcomes can be compared under a defined allocation process. This study is listed as single-group, with allocation NA and no masking, and the registry flags it as not a randomized comparison. General statistical principle: without a suitable concurrent control group, observed outcomes describe the enrolled group but cannot isolate the effect of treatment from other possible influences. The record does not report an alternative comparison strategy.
What does a participant count represent?
The primary endpoint is a count of participants meeting the stated antibody outcome, rather than a continuous measurement such as a concentration or a time-to-event outcome. General statistical principle: a binary participant outcome is commonly reported as the number meeting the definition alongside the number assessed. The number assessed matters because it defines the denominator for interpreting the count. Here, the registry reports enrollment of 2 but does not report the primary endpoint result or its analysis denominator. Enrollment should not be substituted for the number assessed.
A count alone can be useful descriptively, especially when the target is whether an outcome was observed. It does not describe the range of individual measurements or the timing of an event. For the antibody endpoint, interpretation would also depend on the assay, threshold, sampling schedule, and handling of repeated measurements. These details are not reported in the registry record. The endpoint timeframe, up to 18 months, identifies the stated follow-up window but does not specify when samples were taken or how the window was applied to individual participants.
How should uncertainty be considered?
General statistical principle: a confidence interval expresses the range of values compatible with the observed data under a specified statistical model. It can help show how imprecisely an estimate is measured. No confidence interval is reported for the primary endpoint, and no endpoint estimate is reported from which to assess uncertainty. With enrollment of 2, any estimate based on the study would be highly dependent on the observations contributed by the enrolled participants; the registry record does not provide enough information to quantify that uncertainty.
Statistical tests and p-values address a specified hypothesis under model assumptions. They do not supply a missing outcome count, establish causality in a nonrandomized single-group design, or demonstrate clinical importance. No primary-endpoint p-value or test is reported in the registry record. The absence of a listed analysis should not be interpreted as a test result, and it does not show that a particular hypothesis was confirmed or rejected.
Why can over-dispersion matter?
General statistical principle: count data are sometimes analyzed using models that assume a particular relationship between the mean and variability. If observed variation exceeds that assumption, known as over-dispersion, standard errors can be too small and intervals or tests may appear more certain than warranted. This concept is relevant to count outcomes in general, but the primary endpoint is a count of participants with a binary outcome, and the registry does not report a model for it. There is no basis in the record to claim that over-dispersion was assessed or that a specific count model was used.
Repeated observations can also require methods that account for within-participant dependence. The record does not say whether antibody measurements were repeated, nor does it describe any repeated-measures analysis. It would be speculative to infer such a method from the follow-up timeframe alone.
What do the planning calculations mean?
The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. General statistical principle: sample-size planning calculations estimate the amount of information a future design may need under stated assumptions. They are not observed power, do not demonstrate that a study had adequate power, and do not replace analysis of observed outcomes. The record describes the calculations as planning illustrations, not as the trial's own design.
Those assumptions refer to two-arm allocation, whereas the trial is listed as single-group. They therefore should not be read as a description of the actual trial allocation. The sample-size justification and statistical analysis plan for the study are not reported in the registry record. The posted analysis listing contains 0 analyses, so no analysis method, model specification, or adjustment strategy can be confirmed from that listing.
Finally, the registry lists 31 outcome measures. General statistical principle: when many outcomes are considered, the chance of at least one apparently notable result can increase if each is tested without accounting for multiplicity. The record does not report a multiplicity strategy or identify which outcomes, if any, were treated as confirmatory. No conclusion about such a strategy should be inferred from the number of listed outcomes alone.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Laronidase | 1 | 1 | 100.0% | 2.5% to 100.0% | 20.7% to 100.0% | 15.8% to 98.7% |
R code and output
arm <- c("Laronidase")
n <- c(1)
events <- c(1)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Laronidase 1 1 100.0 2.5 100.0 20.7 100.0 15.8 98.711. Multiplicity, Missing Data and Analysis Populations
The registry lists 31 outcome measures, but the posted analysis listing reports 0 analyses. It does not identify a hierarchy of outcomes, state which outcomes were confirmatory, or describe a plan for controlling multiplicity. General statistical principle: testing many outcomes can make isolated positive findings harder to interpret unless the analysis plan addresses the number and relationship of the tests. The registry information does not establish whether any such plan existed or was used.
The primary endpoint is named, but its result is not reported. No denominator for the primary endpoint, confidence interval, test result, or missing-data method is reported in the registry record. The record also does not state whether any enrolled participant lacked a measurement, withdrew, or had incomplete follow-up. Enrollment of 2 cannot be assumed to equal the endpoint analysis population.
Analysis populations are not described. The registry does not state whether analyses were intended to include all enrolled participants, only those with available measurements, or another defined population. Nor does it explain how any missing observations would be handled. These omissions matter because the denominator and missingness pattern affect the interpretation of a participant count and its uncertainty.
The record does not report interim analyses, stopping rules, or an adjustment for repeated looks at data. It also does not explain the termination. These details should be treated as unreported rather than assumed absent from the underlying study conduct. Without the analysis plan and participant-level disposition information, it is not possible to assess how missing data, multiple outcomes, or analysis-population choices shaped the posted results.
12. 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 |
|---|---|---|---|
| Mothers Treated With Laronidase | 0 | 1 | 0.0% |
| Infants Who Were Breastfeed | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Mothers Treated With Laronidase | 0 of 1 |
| Infants Who Were Breastfeed | 0 of 1 |
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 |
|---|---|
| Mothers Treated With Laronidase | 1 of 1 |
| Infants Who Were Breastfeed | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Mothers Treated With Laronidase | Infants Who Were Breastfeed |
|---|---|---|---|
| Tachycardia | Cardiac disorders | 1 of 1 | 0 of 1 |
| Influenza | Infections and infestations | 1 of 1 | 0 of 1 |
| Perinatal depression | Psychiatric disorders | 1 of 1 | 0 of 1 |
| Rhinitis | Infections and infestations | 0 of 1 | 1 of 1 |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | 0 of 1 | 1 of 1 |
The registry lists separate safety entries for mothers treated with laronidase and infants who were breastfed. For serious adverse events, each group is recorded as having 1 participant at risk and 0 affected. Deaths are listed as 0 in each group. For other adverse events, each group is recorded as having 1 at risk and 1 affected.
These are the group-specific counts as recorded; they should not be combined into a total or treated as a comparison between treatment conditions. Mothers and infants are different populations, and the study has no separate control group. The entries therefore do not estimate a treatment-versus-control difference.
The record does not name the other adverse events in the posted safety details, give further event details, or report whether events were considered related to laronidase. The counts also do not show timing, duration, severity beyond the serious-event classification, or whether an individual experienced more than one event. The figures describe what is recorded, not a complete characterization of safety or a causal assessment.
13. What the Result Does, and Does Not, Mean
The record establishes that a phase 4, open-label, single-group study examined laronidase treatment during breastfeeding in women with MPS I and their breastfed infants. It identifies a primary endpoint concerning the number of lactating women with serum IgG antibodies to laronidase, with a timeframe of up to 18 months. It also states broader interests in laronidase presence in breast milk and infant growth, development, and immunologic response.
Those aims should be distinguished from the available results. The primary endpoint count is not reported in the registry record. The registry's listed enrollment of 2 does not reveal how many participants had endpoint data, what was measured in breast milk, or what occurred among infants. The registry entries therefore do not show whether the primary outcome occurred or establish findings for the broader study questions.
The safety entries report 0 serious adverse events and 0 deaths in each listed group, alongside 1 affected by other adverse events in each group. These counts are specific to the record and do not establish that no other events occurred outside the recorded information, identify the events, or attribute them to treatment. The mother and infant entries are not a control comparison.
More generally, a result observed in a single group would describe that study population; without a suitable comparator, it would not by itself show what would have happened under another treatment condition. The posted information also does not provide precision estimates or an analysis plan. Conclusions should therefore remain limited to the design and counts actually recorded, rather than extending to treatment effects, infant outcomes, or breast-milk exposure that are not reported.
14. Why This Trial Matters Statistically
This study raises a statistically distinctive question because it concerns treatment during lactation and includes both mothers receiving laronidase and their breastfed infants. The primary endpoint is maternal antibody status, while the broader stated purpose includes drug presence in breast milk and infant outcomes. Keeping these questions separate is essential: each requires its own outcome definition, measurement, and interpretation.
The record also illustrates why design and result availability matter as much as a study's topic. It describes an open-label, single-group study, reports enrollment of 2, and does not report the primary endpoint result. Without a control group, an observed outcome could be described but not attributed to treatment through a randomized contrast. Without the endpoint result and its denominator, even a descriptive estimate cannot be evaluated.
The safety entries further demonstrate the need to distinguish populations and event categories. Maternal and infant records are not interchangeable arms in an efficacy comparison, and serious events, other events, and deaths convey different information. Counts without event terms, attribution, or follow-up details have limited interpretive reach.
Finally, the record lists 31 outcome measures and 0 analyses. That combination highlights the value of transparent outcome definitions, analysis plans, population definitions, and missing-data reporting. Statistical clarity is particularly important when a study has limited enrollment and multiple clinical questions: the reader needs to know what was measured, for whom, and with what uncertainty before drawing conclusions.
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.
Several limitations are specific to the information recorded for this study. Enrollment is reported as 2, while the primary endpoint result and its analysis denominator are not reported. The registry record therefore does not allow assessment of the observed antibody count or its precision. It also does not indicate whether all enrolled participants completed follow-up or contributed endpoint measurements.
The single-group, open-label design has no randomized control group. As the registry itself notes, the arms are not a like-for-like control comparison. The mother and infant safety populations cannot serve as treatment and control groups, because they differ by role and exposure context. This design limits causal interpretation even if descriptive outcomes are available.
The study is listed as terminated, but the reason is not reported in the registry record. The record does not explain whether termination influenced enrollment, follow-up, outcome collection, or analysis. A protocol, sample-size justification, detailed statistical analysis plan, and analysis-population definitions are also not reported.
Although 31 outcome measures are listed, the posted analysis listing contains 0 analyses. The record does not specify a multiplicity strategy, missing-data approach, or whether outcome definitions were changed. For the safety entries, event terms and attribution are not stated in the registry record recorded, limiting interpretation of the counts. The broader outcomes named in the study purpose, including breast-milk presence and infant growth, development, and immunologic response, do not have results reported in the registry information.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study of the Effect of Aldurazyme® (Laronidase) Treatment on Lactation in Female Patients With Mucopolysaccharidosis I (MPS I) and Their Breastfed Infants — NCT00418821.
- Registry record last updated 2024-02-20; status last verified 2024-02.
- Results first posted 2024-02-20.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry describes NCT00418821 as a phase 4, multicenter, multinational, open-label, single-group study of laronidase treatment during breastfeeding in women with MPS I and their breastfed infants. Allocation is listed as NA, masking as none, enrollment as 2, and status as terminated. The primary endpoint is the number of lactating women with serum IgG antibodies to laronidase over a timeframe of up to 18 months.
The primary endpoint result is not reported in the registry record. The listed safety entries show 0 serious adverse events and 0 deaths for each group, and 1 affected by other adverse events in each group. The registry lists 31 outcome measures and 0 analyses. The reason for termination, analysis populations, missing-data methods, and detailed statistical plan are not reported.