Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function (NCT02795676), a randomized phase 3 study. The primary outcome is Annualized Change (Slope) in Estimated Glomerular Filtration Rate (eGFR).

2. Clinical Question

The primary measure was each participant’s estimated annualized change, or slope, in eGFR. A slope summarizes the direction and rate of change across repeated eGFR assessments rather than relying on a single measurement. The registry reports the median of these individual slopes for each group and a regression-based comparison between groups.

This question concerns a particular study population: people with Fabry disease who had already received agalsidase beta and were eligible for a switch or continuation strategy. The results therefore describe the comparison in that setting. They do not by themselves establish what would happen in people who had not previously received agalsidase beta or in other clinical populations. The registry record does not report a non-inferiority margin, so the threshold used to judge whether the comparison met the non-inferiority criterion is not available in the record.

3. Trial Design

This was a randomized, double-blind, active-control, parallel-group phase 3 study. The registry reports quadruple masking, randomized allocation, and a parallel model. Its stated enrollment was 78. The study was sponsored by Protalix and is recorded as completed; the recorded start was 2016-06 and primary completion was 2021-10.

Participants with Fabry disease and impaired renal function had previously been treated with agalsidase beta. According to the study description, they had received that therapy for approximately 1 year and remained on a stable dose for at least 6 months before entering the randomized comparison. Randomization assigned participants in a 2:1 ratio either to switch to PRX-102 (pegunigalsidase alfa) or to continue agalsidase beta. Both regimens were intravenous infusions every two weeks at 1 mg/kg.

The active-control design compares the new study regimen with an established active study treatment rather than with no treatment or placebo. The parallel-group structure means participants were assigned to one regimen for the comparison, rather than crossing between regimens as part of the recorded design. The registry describes the study as double-blind in its summary and records quadruple masking in its design fields; the exact roles covered by that masking description are not reported in the registry record.

The primary endpoint was the annualized change in eGFR over 24 months. The registry lists secondary outcomes covering eGFR, plasma Lyso-Gb3, pain, disease severity, urine protein/creatinine ratio, and left ventricular mass index. The posted results include outcome summaries for 51 participants in the PRX-102 group and 25 in the agalsidase beta group for the primary endpoint. Those endpoint counts should not be confused with the stated overall enrollment: the primary analysis population had additional eGFR-observation requirements described in the registry.

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: Of the 78 randomized patients, 53 were assigned to the PRX-102 arm and 25 to the agalsidase beta arm. One PRX-102 patient withdrew consent before receiving the study product; accordingly, 77 patients were treated, 52 in the PRX-102 arm and 25 in the agalsidase beta arm.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Intent to Treat (ITT) population includes all randomized patients who received at least one dose of the assigned study medication with at least 4 eGFR observations. For 1 patient with fewer than 4 eGFR observations, the slope was missing.

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 Annualized Change (Slope) in Estimated Glomerular Filtration Rate (eGFR), measured over 24 months.

The primary endpoint is the annualized change, or slope, in estimated glomerular filtration rate (eGFR), expressed in mL/min/1.73 m^2/year, over a timeframe of 24 months. eGFR is an estimate of kidney filtration. The endpoint uses repeated eGFR assessments to estimate each participant’s rate of change over time, rather than treating one measurement as the whole outcome.

For each participant with at least 4 eGFR observations, the registry says an individual annualized mean change was estimated. A participant with fewer than 4 observations had a missing slope. The group result is reported as a median, which describes the middle of the distribution of individual slopes and is less driven by extreme values than an arithmetic mean can be. A negative slope indicates that eGFR declined over the observation period; the size and uncertainty of the group summaries remain important to interpretation.

Using a slope can make use of the pattern of measurements over time and express change on an annualized scale. It can also be sensitive to how repeated measurements are obtained and to which participants have enough observations to contribute. The registry record does not report the detailed model used to estimate each individual slope, beyond describing it as derived from eGFR assessments over time. The reported group medians and confidence intervals therefore need to be read alongside the stated eligibility rule for the endpoint and the missing slope for a participant with fewer than 4 eGFR observations.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a repeated-measure outcome summarized as individual annualized eGFR slopes and then as a median in each group. Its reported unit, mL/min/1.73 m^2/year, expresses the estimated rate of eGFR change on an annualized scale. The registry describes the slope as derived from assessments over time, for up to 24 months. It requires at least 4 eGFR observations to estimate a participant’s slope; a slope is missing when fewer observations are available.

What does the median describe?

The median is the central value after observations are ordered. It gives a measure of the typical location of the participant-level slopes without requiring unusually large or small values to have as much influence as they can have on a mean. It does not show how tightly individual slopes cluster around that value. The reported confidence interval adds information about uncertainty in the group estimate, but it is not an interval containing most participants’ individual results.

The registry reports a 95% confidence interval for each group median. In general, a confidence interval reflects the uncertainty associated with an estimate under the statistical method used. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. The interval does not remove uncertainty about study design, missing observations, or whether the selected analysis answers the intended clinical question.

How should the group comparison be read?

The posted comparison is described as linear regression, with the parameter labelled median difference in final values. The reported estimate is -0.359, and the 95% confidence interval ranges from -2.444 to 1.726. No p-value is reported. The analysis is classified as non-inferiority, but the non-inferiority margin is not reported in the registry record. Without that margin, the interval cannot be assessed against the study’s decision threshold from the registry information alone.

In general, non-inferiority testing asks whether the results rule out a disadvantage larger than a prespecified acceptable margin. This is different from simply asking whether a comparison is statistically distinguishable from zero. A confidence interval that includes zero can still be consistent with non-inferiority if the entire interval is within the permitted margin; conversely, a point estimate close to zero is not enough by itself. Since the margin is not reported, neither conclusion can be drawn from the listed estimate and interval alone.

The displayed medians summarize individual slopes, whereas the sponsor’s comparison is described using final values. These are not necessarily the same estimand or calculation. The registry does not report enough detail to reconstruct the regression procedure, its covariates, or the exact contrast coding. General statistical practice cautions against deriving a comparison by subtracting group summaries unless that subtraction is the stated analysis.

Why do the observation requirements matter?

The stated endpoint population includes randomized participants who received at least one dose of assigned medication and had at least 4 eGFR observations. The registry notes that one participant with fewer than 4 observations had a missing slope. Repeated-measure endpoints can be affected when participants contribute different numbers of observations or when outcomes are unavailable. The registry record does not report the reasons for that participant’s limited observations, a broader missing-data strategy, or sensitivity analyses addressing missing slopes.

In general, missingness matters because an analysis based on observed data can be misleading if the availability of measurements is related to the outcome or to other characteristics relevant to the comparison. This is a general consideration, not evidence that such a problem occurred in this study. The registry provides the observation threshold and the noted missing slope, but not a fuller account of missing-data assumptions or methods.

What do the planning assumptions mean?

The planning illustrations are described as using the observed effect, with a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The target effect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence about the probability that the study result is correct. The randomized allocation in the study itself was 2:1, whereas the planning assumptions use equal allocation. The registry record does not report that these illustrations were the trial’s own design calculation or provide the protocol’s sample-size justification.

In general, planning calculations depend on assumptions about the effect to detect, variability, allocation, and statistical approach. Changing those assumptions changes the sample size a calculation would suggest. They do not change the observed estimate or its uncertainty after the study is complete. The study’s actual analysis and its reported confidence interval should be considered separately from planning illustrations.

Why can over-dispersion matter in count outcomes?

Over-dispersion is a general issue in count data: observed variability can exceed what a simple statistical model assumes. When that happens, standard errors and intervals from an unsuitable model may be too small or otherwise poorly calibrated. The primary endpoint is a continuous eGFR slope, not a count outcome, so over-dispersion is not the central issue for its reported comparison. It can matter in other settings, such as analyses of event counts, but the registry record does not describe an over-dispersion adjustment for this primary endpoint.

10. Analyses Reported by the Sponsor

The registry’s reported comparison is a linear regression analysis labelled non-inferiority. It gives a median difference in final values of -0.359, with a 95% confidence interval from -2.444 to 1.726. The registry does not report a p-value or the non-inferiority margin. Those omissions prevent a complete assessment of the stated non-inferiority decision from the registry record alone.

The group-specific results are medians of individual annualized eGFR slopes, while the reported regression parameter is described as a difference in final values. A simple unadjusted recalculation from group summaries would not necessarily reproduce that regression analysis, because the quantities and methods need not match. No separate recalculated comparison is posted in the registry information, and no discrepancy is flagged. When a sponsor’s analysis differs from a simple unadjusted recalculation, the sponsor’s own analysis takes precedence; that situation is not indicated in this record.

The reported estimate should therefore be read as the sponsor’s stated model-based comparison, with its confidence interval, rather than as a difference reconstructed from the group medians. Neither the interval nor its point estimate can be judged against a non-inferiority margin that is not reported. The available information does not support a definitive conclusion about whether the prespecified non-inferiority criterion was met.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven secondary outcomes: eGFR, plasma Lyso-Gb3, the Short Form Brief Pain Inventory, the Mainz Severity Score Index, urine protein/creatinine ratio, and left ventricular mass index for participants with and without hypertrophy at baseline. It records eight outcome measures overall and one analysis. The primary endpoint is the annualized change in eGFR; the listed secondary outcomes cover additional laboratory, symptom, disease-severity, renal, and cardiac measures.

When a study examines multiple outcomes or multiple comparisons, the chance of at least one apparently notable result can increase. Statistical methods sometimes address this multiplicity, but the registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a detailed plan for interpreting them together. The absence of that information does not show that no such plan existed; it means the plan is not reported in the registry record. Secondary findings should not be treated as confirmatory without knowing how they were selected and interpreted.

The primary population is described as randomized participants who received at least one dose of assigned study medication and had at least 4 eGFR observations. The registry says one participant with fewer than 4 observations had a missing slope. The endpoint counts are 51 for PRX-102 and 25 for agalsidase beta. The record does not report a fuller accounting of all randomized participants by analysis population, the reasons for missing observations, or sensitivity analyses for missing slopes.

The term ITT is used in the registry description, but its accompanying definition includes receipt of at least one dose and the minimum eGFR-observation requirement. That definition is narrower than the common broad use of intention-to-treat, which generally retains randomized participants in their assigned groups regardless of treatment received or outcome availability. The record’s stated population definition should therefore be kept in view when interpreting the endpoint results. Details of any separate safety or other analysis populations, and the statistical methods for missing data, are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: chest pain (8.0%), acute respiratory failure (4.0%), chronic obstructive pulmonary disease (4.0%), suicidal ideation (4.0%), atrial fibrillation (4.0%).

The registry reports serious adverse events among 8 of 52 participants at risk in the PRX-102 group and 6 of 25 in the agalsidase beta group. It reports other adverse events among 47 of 52 and 24 of 25 participants at risk, respectively. The recorded number of deaths is 0 in each group. These are participant counts, not event counts; one participant may experience more than one event, and the figures alone do not describe event timing, duration, or severity beyond the serious-event classification.

The registry lists chest pain at 8.0% and acute respiratory failure, chronic obstructive pulmonary disease, suicidal ideation, atrial fibrillation, and tachycardia at 4.0% each among the top serious terms. The record does not identify the treatment group for each listed term in the information, so these percentages should not be attributed to a particular group. A listed term also does not reveal whether events were considered related to study treatment.

These figures describe the posted safety experience and should be interpreted with their denominators and the study’s size in mind. Counts across groups are not, by themselves, a causal comparison. The registry record does not provide the detailed event narratives, exposure-adjusted analyses, or attribution information needed for a fuller assessment. These safety summaries do not constitute medical advice.

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

The primary results describe negative median annualized eGFR slopes in both randomized groups over the 24-month endpoint timeframe. The estimated median was -2.514 mL/min/1.73 m^2/year for PRX-102 and -2.155 mL/min/1.73 m^2/year for agalsidase beta. The confidence intervals indicate uncertainty around both estimates, and their ranges do not establish the distribution of individual participants’ outcomes.

The reported regression comparison is -0.359, with a 95% confidence interval from -2.444 to 1.726. The estimate is accompanied by substantial uncertainty in the sense that the interval covers values on either side of zero. Because the non-inferiority margin is not reported, the interval cannot establish whether the trial’s stated non-inferiority criterion was satisfied. A result that does not show a clear difference from zero is not automatically evidence of equivalence or non-inferiority.

The findings apply to the study population and endpoint definition recorded: people with Fabry disease previously treated with agalsidase beta, with the primary endpoint requiring at least 4 eGFR observations. The study compared switching to PRX-102 with continuing agalsidase beta under the recorded dosing schedules. The results do not establish effects in populations not represented by this study or answer questions about outcomes beyond those measured and reported.

The primary endpoint is one part of the evidence. It does not summarize all secondary outcomes or safety events, and the registry record does not report enough detail to judge every aspect of the analysis plan, missing-data approach, or non-inferiority decision rule. A confidence interval communicates precision under an analysis; it cannot compensate for unreported design details. These statistical results describe a group comparison and should not be converted into advice about a person’s treatment.

14. Why This Trial Matters Statistically

This trial is statistically notable because it evaluates a switch-versus-continue question in an active-control design. Participants had prior agalsidase beta exposure, and the randomized comparison was between switching to PRX-102 and continuing agalsidase beta. That design makes the interpretation depend on the comparison between groups, not on whether either group’s eGFR changed from its own baseline in isolation.

The primary endpoint also illustrates the distinction between a participant-level trajectory and a group-level summary. Individual eGFR slopes were estimated from repeated measurements, then summarized by group medians. The reported regression comparison is described using final values, so it should not be assumed to be a direct difference between those medians. Keeping the estimand and method clear is essential when reading a trial result.

Non-inferiority studies require a prespecified margin that defines the largest acceptable disadvantage. The registry labels the analysis non-inferiority but does not report that margin. This gap limits how completely a reader can evaluate the decision, even though an estimate and confidence interval are posted. It also shows why a confidence interval’s relation to zero is not a substitute for comparison with the appropriate non-inferiority threshold.

The endpoint population has an explicit minimum-observation rule, and one participant’s slope was missing for not meeting it. That detail matters because the observed analysis is tied to who had sufficient measurements. Together, the design, endpoint definition, comparison method, and missing information determine what can reasonably be concluded from the posted statistics.

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 registry record does not report the non-inferiority margin, so the stated non-inferiority comparison cannot be fully assessed against its decision threshold. It also does not report a p-value for the comparison. The estimate and confidence interval are available, but neither supplies the missing margin or complete decision rule.

The sponsor’s comparison is described as linear regression with a median difference in final values, while the group summaries are medians of annualized individual eGFR slopes. The registry does not report enough detail about the regression specification, covariates, or contrast coding to reconstruct the analysis. The group medians should not be treated as if their difference were the reported model-based result.

The endpoint population requires at least 4 eGFR observations, and the registry notes one missing slope because a participant had fewer observations. Reasons for missing measurements, a comprehensive missing-data method, and sensitivity analyses are not reported in the registry record. The exact roles included in the quadruple-masking designation are also not reported.

The record lists secondary outcomes but does not report a multiplicity strategy or hierarchy for interpreting them. It does not report the trial’s sample-size justification, detailed statistical analysis plan, or interim analyses. Planning illustrations based on the observed effect are not the same as the trial’s own design rationale or observed power. Finally, the safety counts and listed serious-event terms do not include all contextual details needed to interpret event attribution, timing, or exposure. These limitations concern what can be assessed from the registry record; they do not establish that unreported methods or details were absent from the full study materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function — NCT02795676.
• Registry record last updated 2023-09-13; status last verified 2023-09.
• Results first posted 2023-08-02.
• 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

NCT02795676 is a completed randomized phase 3 study comparing PRX-102 (pegunigalsidase alfa) with agalsidase beta in people with Fabry disease previously treated with agalsidase beta. The registry records enrollment of 78, quadruple masking, and a parallel design. Participants were randomized in a 2:1 ratio to switch treatment or continue agalsidase beta; both regimens were intravenous infusions every two weeks at 1 mg/kg.

The primary endpoint was the median annualized change in eGFR over 24 months. The posted group medians were -2.514 mL/min/1.73 m^2/year for PRX-102 and -2.155 mL/min/1.73 m^2/year for agalsidase beta. The reported regression comparison was -0.359, with a 95% confidence interval from -2.444 to 1.726, and was labelled non-inferiority. The registry record does not report the margin needed to assess that designation fully.

The registry also lists secondary outcomes and adverse-event summaries. The primary endpoint population required at least 4 eGFR observations; one participant with fewer observations had a missing slope. Further details about missing-data methods, multiplicity, and the full analysis plan are not reported in the registry record.