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 Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-naïve Adult Male Patients With Fabry Disease (NCT02228460), a na phase 2 study. The primary outcome is Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02228460 |
| Phase | Phase 2 |
| Condition | Fabry Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genzyme, a Sanofi Company |
| Results posted | Yes |
2. Clinical Question
Population
Adult male participants diagnosed with Fabry disease who were treatment-naïve to enzyme replacement therapy (ERT). The primary analysis population was the full analysis set: participants who received at least 1 dose of study treatment. For the primary endpoint, the number analyzed was limited to participants with available data at both Baseline and Week 26.
Intervention
GZ/SAR402671, given orally at 15 milligram (mg) once daily for 26 weeks.
Comparator
There was no separate control group. The study is recorded as a single-group trial with allocation listed as NA and no masking.
Primary question
How many participants shifted between categories of skin GL-3 accumulation severity from Baseline to Week 26 in superficial skin capillary endothelium? The registry record names this as an exploratory efficacy endpoint, alongside safety, pharmacokinetics, and pharmacodynamics objectives.
The primary endpoint uses a skin biopsy score to describe GL-3 accumulation in a particular cell type. Pathologists assigned severity ratings at Baseline and Week 26, and participant counts were to be summarized by the category of change between those assessments. A shift to a lower score was defined as indicating less severe condition at Week 26. The registry record does not report the counts in the shift categories, the number with paired biopsy data, or a numerical treatment effect. Consequently, the stated question can be described from the outcome definition, but the endpoint result cannot be assessed from the registry record.
Because the trial had no control group, any observed change would describe participants over time during treatment, rather than directly compare treatment with an alternative. The record does not establish how changes would differ from changes without treatment or under another treatment. The primary endpoint is one part of a broader set of measures that includes plasma and urine biomarkers, skin-cell scores, and treatment-emergent adverse events.
3. Trial Design
This completed Phase 2 study enrolled 11 treatment-naïve adult male participants diagnosed with Fabry disease. It was a single-group study of GZ/SAR402671, with no masking and allocation recorded as NA. Participants received the study drug orally at 15 milligram (mg) once daily for 26 weeks. The study began in 2014-11 and reached primary completion in 2016-09. The sponsor listed in the registry record is Genzyme, a Sanofi Company.
The study's stated primary objective was to assess safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy. The primary endpoint described in the record was a count of participants in categories of shift in skin GL-3 score in superficial skin capillary endothelium, from Baseline to Week 26. This was a within-participant measurement over time, not a randomized comparison between groups.
The registry record lists 20 outcome measures and two analysis entries. Secondary outcomes include changes from Baseline in plasma GL-3, plasma Lyso-GL-3, plasma GL-1, and urine GL-3 concentrations at Week 26. Other listed outcomes count participants by shift categories for skin GL-3 scores in deep-vessel endothelial cells, deep-vessel smooth muscle cells, and perineurium cells. Treatment-emergent adverse events are also listed. The record does not give detailed results for these measures in the information available for this trial description.
A single-group design can describe measurements and events among participants who received the study drug. It cannot, by itself, separate treatment-associated change from natural variation over time, changes related to study participation, or other influences. The registry record does not report a control group, a randomization procedure, masking, or an allocation ratio. It also does not report a statistical analysis plan or the rationale used to choose the enrollment target. These omissions limit how fully the design and its intended inferential framework can be reconstructed.
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: Out of 14 screened participants, 11 participants were enrolled and treated in the study.
Overall Study
| Stage | GZ/SAR402671 |
|---|---|
| STARTED | 11 |
| COMPLETED | 9 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | GZ/SAR402671 |
|---|---|
| Adverse Event | 1 |
| Lost to Follow-up | 1 |
Analysis population for the primary outcome, as defined in the registry: Analysis was performed on full analysis set (FAS) that included all participants who received at least 1 dose of study treatment. Here, 'overall number of participants analyzed' = participants with available data at both Baseline and Week 26.
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: Analysis was performed on full analysis set (FAS) that included all participants who received at least 1 dose of study treatment.
| Characteristic | Unit | GZ/SAR402671 |
|---|---|---|
| Participants analysed | 11 | |
| Age, Continuous | years | 26.5 (SD 7.6) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26, measured over Baseline, Week 26.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants according to how their skin GL-3 severity score changed from Baseline to Week 26 in superficial skin capillary endothelium. Skin biopsies were evaluated by light microscopy for cellular GL-3 accumulation, described as inclusions. Three independent pathologists rated each biopsy on a scale from 0 (none/trace) to 3 (severe), with higher scores indicating more severe condition. A participant's score at each time point was the rating agreed on by a majority of pathologists; if no majority score could be derived, the median score was used.
The endpoint is a categorical shift summary: each participant with paired data can be placed according to the Baseline and Week 26 scores. The registry description states that a shift to a lower score indicates less severe condition at Week 26. This approach retains information about direction of change rather than reducing the two assessments to a single follow-up score. It also makes the underlying score interpretation explicit: a larger severity score means greater observed GL-3 accumulation.
Skin tissue is used as a biological measure of GL-3 accumulation in specified cell types. The endpoint is not a direct count of symptoms, functional status, or clinical events. The record does not report the observed shift-category counts, paired-data total, or a summary estimate of change. It also notes that shift categories not observed were not reported, so the absence of a category from a result display would not establish that a participant had that shift; the registry result itself is not reported in the information available for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a primary endpoint but does not report its numerical result. It gives no count of participants in any Baseline-to-Week 26 shift category, no total with paired biopsy data, and no statistical estimate or uncertainty interval for the endpoint. The endpoint's direction is defined: a shift to a lower score corresponds to less severe condition at Week 26. Without the category counts, however, the direction or distribution of observed changes cannot be determined.
The enrollment was 11, and the primary analysis population was defined as participants who received at least 1 dose of study treatment. For this endpoint, the record further defines the overall number analyzed as participants with data at both Baseline and Week 26. The number meeting that paired-data requirement is not reported in the registry record. Thus the enrollment figure should not be mistaken for the primary endpoint's analyzed sample size.
The endpoint is a count across ordinal shift categories, not a mean score difference as described in the primary outcome title. The score levels convey an ordered severity scale, while the result is intended to count participants by transition between Baseline and follow-up. A shift summary can communicate whether participants moved toward lower, unchanged, or higher score categories, but its interpretation depends on the actual counts and category definitions reported. Those counts are unavailable in the registry record, and categories with no observed participants were explicitly not reported.
There was no separate control group. Even if a within-group change were available, it would describe the observed course among participants receiving GZ/SAR402671 during the study period. It would not estimate a contrast with no treatment or another therapy. Changes may reflect several influences, and a single-group result cannot distinguish those influences on its own. No causal comparison should be inferred from a Baseline-to-Week 26 measurement.
The study also included safety, pharmacokinetic, pharmacodynamic, and exploratory efficacy objectives, with listed outcomes covering multiple biomarkers, several skin cell types, and adverse events. The registry record does not report the results needed to interpret most of those outcomes in this account. The serious adverse event information is summarized separately, but event counts alone do not establish whether an event was caused by treatment. Overall, the record supports a description of the trial design and planned endpoint definitions, not a conclusion about the size, precision, or clinical meaning of the primary endpoint result.
9. Statistical Methods Explained
What does a shift endpoint describe?
A shift endpoint organizes paired assessments by the participant's starting category and later category. For this study, the categories arise from an ordered skin GL-3 severity score. The paired approach preserves whether a participant's score category went to a lower, same, or higher level between Baseline and Week 26. It is different from reporting only an average follow-up score, because it explicitly uses each participant's starting category. It is also different from a continuous outcome such as a mean change, because the posted endpoint is a count of participants in shift categories.
Ordinal scores have order, but the spacing between successive scores is not necessarily equal. A transition between two adjacent categories and a transition across more than one category can therefore be described as distinct shifts without assuming equal numerical distances have the same meaning. The registry record does not report the observed category counts, so the pattern of transitions cannot be assessed.
How was the score assigned?
Three independent pathologists evaluated each skin biopsy under light microscopy for cellular GL-3 accumulation. Each used a severity scale from 0 (none/trace) through 3 (severe), with higher values corresponding to more severe condition. The participant-level score at a time point came from the score rated by a majority of pathologists. If a majority score could not be derived, the median score was used. This rule provides a defined way to convert multiple readings into one score for each participant at each time point. The registry record does not provide information on agreement among pathologists or how often the median rule was needed.
What does the analysis population mean?
The full analysis set included all participants who received at least 1 dose of study treatment. For the primary endpoint, the overall number analyzed was specifically the participants with available data at both Baseline and Week 26. That paired-data requirement is important: a participant without an assessment at either time point cannot be assigned a Baseline-to-Week 26 shift based on observed paired scores. The number of participants with paired observations is not reported in the registry record.
General statistical principle: an analysis population definition determines which participants contribute to a particular result. A population based on receiving treatment is not automatically identical to the population with complete outcome data. When the outcome requires two time points, missing data at either time can reduce the number with usable paired observations. The registry record does not describe imputation, sensitivity analyses, or other methods for handling missing endpoint data.
What can a single-group analysis establish?
The trial has one treatment group and no control group. General statistical principle: a within-group comparison over time describes observed change but does not supply the counterfactual comparison needed to determine what would have happened to the same participants without the treatment. This matters even when an endpoint is measured at Baseline and follow-up, because time, measurement variation, and other influences can also contribute to change. The design therefore supports descriptive interpretation of the treated group, but not a randomized estimate of treatment effect against a comparator.
The registry record lists two analysis entries, but does not report their statistical methods in the information available for this account. It does not specify a model for the shift categories, a hypothesis test, an effect estimate, a confidence interval, or an analysis adjustment. Those details should not be inferred from the endpoint format. General statistical principle: a confidence interval, when reported, describes uncertainty around an estimate under the assumptions of the analysis; it does not remove design limitations such as the absence of a control group.
Why does multiplicity matter?
The record lists 20 outcome measures, spanning safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy. When many outcomes or comparisons are examined, the chance of finding a seemingly notable result by chance can increase if results are interpreted as confirmatory without accounting for the number of analyses. General statistical principle: multiplicity procedures can control error rates across a defined family of tests, but their use depends on a specified analysis plan. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or a prespecified testing strategy. It is therefore not possible to determine whether or how multiplicity was addressed.
What statistical plan is documented?
The primary endpoint description gives scoring and population definitions, but a complete statistical analysis plan is not reported in the registry record. In particular, no model, inferential procedure, missing-data method, or precision measure is described for the primary endpoint in the available information. General statistical principle: interpretation should distinguish a defined outcome from a defined inferential analysis. The existence of an endpoint definition does not establish which statistical method was used or whether a formal treatment-effect hypothesis was tested.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 20 outcome measures, including a primary skin GL-3 shift endpoint, biomarker measures, skin-cell shift outcomes, and treatment-emergent adverse events. It does not report a multiplicity strategy, such as a hierarchy of hypotheses or an adjustment for evaluating multiple outcomes. Without such information, the intended confirmatory status of individual results and the handling of multiple statistical tests cannot be determined. The study's stated objectives include exploratory efficacy, but the record does not provide a more detailed statistical plan.
The primary analysis population is the full analysis set, defined as participants who received at least 1 dose of study treatment. For the primary endpoint, the analyzed total is further defined as those with available data at both Baseline and Week 26. This definition identifies a paired-observation requirement, but the number of participants with such data is not reported. The registry record does not state whether missing values were imputed, whether participants with incomplete paired assessments were excluded from other analyses, or whether sensitivity analyses were conducted.
The outcome description says that any shift category not observed is not reported. This is a reporting convention for empty categories, not a missing-data procedure. A category omitted because it had no observed participants is distinct from a participant who could not be classified because a Baseline or Week 26 score was unavailable. The record does not report the number of participants in either situation.
General statistical principle: missing outcome data can affect both the number of observations contributing to an analysis and the interpretation of the result, particularly if missingness is related to participant characteristics or outcomes. No assumptions about the cause or treatment of missingness can be made from the registry record. The absence of a stated method should not be read as evidence that a particular approach was or was not used.
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 |
|---|---|---|---|
| GZ/SAR402671 | 3 | 11 | 27.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| GZ/SAR402671 | 0 of 11 |
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 |
|---|---|
| GZ/SAR402671 | 9 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | GZ/SAR402671 |
|---|---|---|
| Haemolysis | Blood and lymphatic system disorders | 1 of 11 |
| Floppy infant | Musculoskeletal and connective tissue disorders | 1 of 11 |
| Depressed mood | Psychiatric disorders | 1 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GZ/SAR402671 |
|---|---|---|
| Headache | Nervous system disorders | 4 of 11 |
| Tinnitus | Ear and labyrinth disorders | 2 of 11 |
| Nausea | Gastrointestinal disorders | 2 of 11 |
| Vomiting | Gastrointestinal disorders | 2 of 11 |
| Fatigue | General disorders | 2 of 11 |
| Feeling hot | General disorders | 2 of 11 |
| Pyrexia | General disorders | 2 of 11 |
| Rhinitis | Infections and infestations | 2 of 11 |
| Upper respiratory tract infection | Infections and infestations | 2 of 11 |
| Dizziness | Nervous system disorders | 2 of 11 |
Serious events with the highest arm-level rate: haemolysis (9.1%), floppy infant (9.1%), depressed mood (9.1%).
The serious adverse event figures list 11 participants at risk and 3 participants affected in the GZ/SAR402671 group. The registry record also lists 11 participants at risk and 9 participants affected for other adverse events. These are participant counts in the safety summary; they do not describe event severity beyond the serious-versus-other classification, duration, recurrence, or causal relationship to treatment. The record lists 0 deaths.
Three serious event terms are identified, each with a listed frequency of 9.1%: Haemolysis, Floppy infant, and Depressed mood. These terms describe events recorded in the registry; they do not by themselves show that the study drug caused them. Counts and percentages in a small single-group study are descriptive and provide limited information about how frequently events might occur in a broader population. The registry record does not provide additional clinical context for these terms in the information, nor does it report a comparator group for assessing relative event frequency.
Serious adverse events and other adverse events are separate summaries in the record. Their affected-participant counts should not be combined or interpreted as mutually exclusive without participant-level details. The record does not state whether any participant experienced more than one event or appeared in more than one category. Safety counts indicate what was reported during the study, not a causal conclusion about treatment.
12. What the Result Does, and Does Not, Mean
This study describes a Phase 2 evaluation of GZ/SAR402671 in treatment-naïve adult men with Fabry disease. The registry record specifies a daily oral regimen lasting 26 weeks and defines a primary endpoint based on changes in skin GL-3 severity categories between Baseline and Week 26. It also lists safety, pharmacokinetic, pharmacodynamic, biomarker, and other skin-cell outcomes.
The primary endpoint definition explains how biopsies were scored and how multiple pathologist ratings were converted to participant-level values. It also defines a lower score at Week 26 as a shift indicating less severe condition. But the registry record does not report the primary endpoint's shift-category counts, the number analyzed with paired biopsies, or a statistical estimate. The direction and magnitude of observed endpoint changes therefore cannot be established from the record. An outcome definition is not itself an outcome result.
The design is single-group, unmasked, and has no control arm. Any reported Baseline-to-Week 26 change would describe participants over time during the study, not a comparison with an untreated or alternatively treated group. Such a change would not, on its own, identify what caused the change. No treatment-effect estimate against a comparator can be derived from the design information.
The safety summary reports 3 participants with serious adverse events among 11 at risk, 9 participants with other adverse events among 11 at risk, and 0 deaths. The listed serious event terms and their percentages are descriptive registry entries. They do not establish causation or provide a controlled estimate of safety.
Accordingly, the record supports conclusions about the study's design, endpoint definitions, and reported safety counts. It does not support a conclusion about the numerical primary endpoint result, its precision, or a comparative treatment effect. The registry record does not report the statistical plan, multiplicity approach, or missing-data methods needed to assess those aspects further.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how a biological endpoint can be defined in a small, single-group study. Its primary measure is not simply a follow-up score: it counts participants by transitions between Baseline and Week 26 categories of skin GL-3 severity. The record also describes a consensus procedure for converting three pathologist ratings into one score at each time point. These details clarify what the endpoint was intended to represent and how it was constructed.
The same design highlights the distinction between descriptive change and comparative evidence. Repeated measurements can show how a group changes over time, but with no control group they cannot isolate the contribution of treatment from other influences. This is a central interpretive issue for single-group studies, especially when the stated efficacy objective is exploratory. The record describes no randomized or like-for-like comparator.
The endpoint also makes missingness consequential: a shift requires a score at both Baseline and Week 26. The full analysis set includes those who received at least 1 dose, while the primary endpoint's analyzed total is limited to participants with available data at both times. Because that total and the shift counts are not reported, readers cannot evaluate endpoint completeness or the observed distribution of changes.
Finally, the registry lists 20 outcome measures across several domains. Without a reported multiplicity strategy or statistical plan, it is not possible to determine how the study distinguished exploratory findings from confirmatory tests or handled the risk of interpreting multiple results. These features make the record useful for understanding outcome construction and design constraints, while also marking clear limits on what can be inferred from the posted information.
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 main trial-specific limitation is the absence of reported primary endpoint results in the registry record. The record does not give participant counts for any shift category, the number with paired Baseline and Week 26 biopsies, or an estimate with a measure of precision. Consequently, the defined endpoint cannot be interpreted as an observed result.
The study enrolled 11 participants and had a single treatment group. This design provides no concurrent comparator for separating changes during follow-up from changes that could have occurred for other reasons. The record lists no masking and no allocation procedure. It does not report details that would permit assessment of how participant selection, adherence, or other trial procedures may have influenced the results.
The primary endpoint depends on skin biopsy assessment and a rule for combining pathologists' scores. Although the scoring scale and majority/median rule are described, the record does not report reader agreement, the frequency of use of the median rule, or the number of evaluable biopsies. It also omits the actual distribution of Baseline scores, which would help characterize the possible shift patterns without implying a treatment effect.
The record lists 20 outcome measures but does not report a multiplicity approach or a complete statistical analysis plan. It does not describe missing-data handling, sensitivity analyses, or the statistical method for the primary endpoint. The information available also does not include detailed results for the listed biomarker and secondary outcomes. These gaps limit assessment of analysis choices, outcome completeness, and the consistency of findings across measures.
Safety figures are descriptive and come from a single-group study. The record does not provide a comparative safety estimate, detailed context for the listed serious event terms, or participant-level information on multiple events. The counts therefore cannot establish whether events were related to treatment or how event frequency compares with another group.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-naïve Adult Male Patients With Fabry Disease — NCT02228460.
- Registry record last updated 2019-12-17; status last verified 2016-09.
- Results first posted 2019-12-17.
- 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
NCT02228460 is a completed Phase 2, single-group study of GZ/SAR402671 in treatment-naïve adult male participants diagnosed with Fabry disease. The study enrolled 11 participants and used an oral dose of 15 milligram (mg) once daily for 26 weeks. It was unmasked, with allocation recorded as NA.
The primary endpoint counted participants by change category in skin GL-3 score in superficial skin capillary endothelium from Baseline to Week 26. Scores were based on biopsy readings by three independent pathologists, using a 0-to-3 severity scale and a majority rating, or the median when no majority was available. The primary analysis set included participants who received at least 1 dose, with the endpoint analyzed among those with data at both time points.
The registry record does not report the primary shift counts, paired-data total, or a statistical analysis plan. It lists 20 outcome measures and two analysis entries. Safety information lists 3 participants with serious adverse events, 9 with other adverse events, and 0 deaths.