Extension Study of PRX-102 for up to 60 Months: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Study of PRX-102 for up to 60 Months (NCT01981720), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03.

2. Clinical Question

3. Trial Design

This completed extension study evaluated PRX-102 in adult Fabry patients who had successfully completed treatment with PRX-102 in studies PB-102-F01 and PB-102-F02. The study title describes treatment for up to 60 months. The intervention is listed as PRX-102 (pegunigalsidase alfa), given by intravenous infusion at 1.0 mg/kg every 2 weeks, with a permitted window of +/- 3 days.

The registry classifies the study as single-group, with allocation listed as NA and masking as none. These features mean that the record does not describe random assignment, masking, or a concurrent control arm. The treatment group is not a like-for-like control comparison, so an observed count within this group cannot by itself establish how the outcome would have differed under another treatment or no treatment.

The recorded enrollment is 15. The study is listed as Phase 1 and Phase 2, with status completed. The recorded start date is 2014-01-16 and the primary completion date is 2020-08-26. These dates describe the registry entry; they do not establish that each participant was followed for the full timeframe stated for the endpoint.

The registry lists three outcome measures and no analysis records. It defines a safety population as all patients who received any dose, partial or complete, of study treatment in PB-102-F03. It defines an efficacy population as all patients who received at least one complete dose. The actual sizes of those populations, and which population was used to calculate the primary endpoint, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 15 adult patients (8 male and 7 female) who completed study PB-102-F02 were enrolled in this study and included in both the Safety and Efficacy populations.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population is defined as all patients who received any dose (partial or complete) of study treatment as part of study PB-102-F03. Efficacy population is defined as all patients who received at least one complete dose of the study treatment as part of study PB-102-F03

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 Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03, measured over Every two weeks up to 60 months.

The primary endpoint is titled “Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03.” Its stated timeframe is every two weeks up to 60 months. The aim is to describe the occurrence of adverse events considered related to study treatment, using the registry’s stated categories of definitely, probably, or possibly related.

There is an important distinction in the endpoint wording: the title specifies a number of participants, while the description says the results represent the number of treatment-emergent adverse events. A participant count and an event count answer different questions. One participant may experience more than one event, so the two measures are not interchangeable. The registry record does not clarify this wording difference or report a primary endpoint value.

In general, adverse-event endpoints are used to characterize safety and tolerability during a study. CTCAE v4.03 is the assessment system named in the record. A count of events or participants can describe what was recorded in the study group, but without a comparison group it does not estimate a treatment-versus-control difference. The registry record does not report the endpoint analysis method, an uncertainty interval, or a relatedness assessment breakdown.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group result describe?

In general, a single-group study describes outcomes among participants who received the study intervention. It can document events recorded during follow-up and provide information about the experience of the enrolled group. It does not directly estimate a treatment contrast, because no comparator group is present. Any interpretation as a treatment effect would require assumptions beyond the observed group’s event count.

That distinction matters for this extension. Allocation is listed as NA, masking as none, and the model as single-group. These registry entries do not describe random assignment or a control arm. Thus, a count of adverse events cannot be interpreted as the difference between PRX-102 and another treatment, nor as evidence that the treatment caused or prevented an event. The record also does not report a causal analysis.

What does a count measure?

A count reports how many people or events meet a defined outcome. Those are different units: a participant can experience multiple events, while a participant-level measure generally counts a person once if the specified condition is met. The primary endpoint title refers to participants, but the description refers to treatment-emergent adverse events. The registry record does not resolve whether the intended result is a participant count, an event count, or both.

In general, counts are easiest to interpret when the outcome definition, observation period, and population are clear. Here, the endpoint timeframe is every two weeks up to 60 months, but the record does not give participant-level follow-up, exposure duration, or a detailed endpoint calculation method. The displayed safety counts should therefore be read as counts in the registry listing rather than as exposure-adjusted rates.

How should uncertainty be considered?

General explanation: a confidence interval describes a range of values compatible with the observed data under a statistical model. It conveys uncertainty around an estimate; it does not remove limitations in study design or establish causality. For a count in a small study, the estimate can be imprecise, and different statistical methods can produce different intervals. The registry record does not report a confidence interval or the method used to calculate one for the primary endpoint.

The absence of a reported interval is especially relevant because the primary endpoint value itself is not reported. Without an estimate, there is no primary endpoint uncertainty to interpret from the registry record. The safety listing supplies selected counts and terms, but no inferential comparison or uncertainty measure for them.

Why is over-dispersion relevant in general?

General explanation: some count-data models assume that variability follows a particular relationship to the average count. When observed variation is larger than that assumption allows, the data are over-dispersed relative to the model. Treating over-dispersed data as less variable than they are can make uncertainty appear too small. Whether over-dispersion is relevant depends on the outcome structure and analysis; the registry record does not report a count model or an assessment of dispersion.

For adverse events, repeated events within a participant can also make event counts dependent rather than independent. A participant-level analysis and an event-level analysis handle that structure differently. The endpoint wording does not make the chosen unit clear, and no analysis method is reported. It is therefore not possible to infer whether repeated events were counted separately or how within-participant clustering was handled.

What do the planning calculations represent?

The sample-size assumptions describe a planning illustration, not the design justification reported for this trial. The stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the stated calculation concerns total events; for other outcomes, it concerns participants per arm.

These assumptions do not turn the single-group extension into a two-arm comparison. They are planning conventions for hypothetical future comparisons, not evidence that the study had those design features. The registry record does not report the trial’s own sample-size justification, and the planning calculations are not observed power. Since this study has no like-for-like control arm, they should not be read as a test of the extension study’s treatment effect.

The registry lists no analysis records. It does not report the statistical model, the handling of missing outcome data, any adjustment for covariates, or a method for constructing intervals. These are material details for interpreting estimates, rather than details that can be inferred from the endpoint title or the single-group design.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and no analysis records. It does not report a multiplicity strategy, such as how the interpretation of several outcomes was coordinated or whether any adjustment was planned. Without that information, it is not possible to determine how multiple outcome assessments were handled in the study’s statistical interpretation.

Missing-data methods are not reported in the registry record. The record does not say how incomplete follow-up, missed assessments, treatment discontinuation, or missing endpoint information were handled. It also does not report how many participants had missing measurements or whether missingness differed by outcome. A lack of reported missing-data information should not be read as evidence that all observations were complete.

The record defines the safety population as all patients who received any dose, partial or complete, of study treatment in PB-102-F03. It defines the efficacy population as patients who received at least one complete dose. These definitions distinguish who may contribute to safety and efficacy evaluations, but the registry record does not report the size of either population or identify the population used for the primary endpoint calculation.

The primary endpoint is described as a count, but the title refers to participants and the description refers to adverse events. This distinction affects how repeat events and incomplete observations might be handled. The registry does not provide enough analysis detail to determine those choices. No adjusted or unadjusted primary endpoint analysis is reported.

11. 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: clavicle fracture (6.7%), chronic obstructive pulmonary disease (6.7%), pneumonia (6.7%).

The safety listing reports 3 affected under its serious-event entries, with 15 at risk, and 15 affected under its other-event entries, also with 15 at risk. It separately lists 1 death. These figures describe the registry’s safety record for the single PRX-102 group; they are not comparative estimates and do not establish causation.

The listed serious-event terms are clavicle fracture, chronic obstructive pulmonary disease, and pneumonia, each reported as 6.7%. The denominator and calculation basis for these percentages are not reported in the registry record. The listed terms should not be taken to represent every event or the full safety profile, since the record identifies them as top serious terms.

Seriousness and treatment relatedness are separate concepts. The primary endpoint concerns treatment-related events, but the serious-event listing does not state that its events were considered related to treatment. The registry record does not report whether the death was related to treatment, nor does it provide a cause of death. These entries should therefore be read as descriptive safety information, not as evidence of a treatment effect.

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

The registry record documents a completed, single-group extension study of PRX-102 in adults with Fabry disease who had successfully completed PRX-102 treatment in earlier studies. It states an intended evaluation of ongoing safety, tolerability, and efficacy parameters, and identifies treatment-related adverse events as the primary endpoint. The record does not report the result for that endpoint, so the primary safety outcome cannot be quantified from the available entry.

The safety listing gives counts for serious and other events, selected serious-event terms, and a death count. Those data provide descriptive information about events recorded in the study group. They do not show whether event occurrence was higher or lower than it would have been under another treatment, and they do not establish that PRX-102 caused or prevented any listed event. The serious-event percentages are listed without a denominator or calculation details.

General statistical explanation: a result is most informative when its outcome definition, analysis population, observation period, uncertainty, and comparison are clear. In this record, the primary endpoint wording differs between its title and description; the analysis method and uncertainty are not reported; and no comparator group is included. Those gaps limit interpretation beyond the reported descriptive entries.

The extension population was defined by prior successful completion of PRX-102 treatment. Its experience cannot automatically be generalized to patients who did not complete the earlier studies or to all adults with Fabry disease. The registry record also does not give individual follow-up durations, so the stated timeframe of up to 60 months should not be interpreted as a uniform duration for every participant.

In short, the record establishes the study’s design and lists some safety information, but it does not report the primary endpoint result or an analysis that would support a comparative treatment conclusion. The listed counts are not a substitute for those missing results.

13. Why This Trial Matters Statistically

This study is statistically useful to consider because it illustrates the difference between descriptive safety follow-up and comparative evidence. A single-group extension can record events during continued treatment among an enrolled cohort. However, without a concurrent comparator, those counts do not estimate how outcomes would differ under another treatment or no treatment.

The population also has a specific entry condition: participants had successfully completed PRX-102 treatment in earlier studies. This makes the cohort relevant to continued treatment in that selected group, while limiting direct generalization beyond it. The eligibility context is part of the meaning of any observed count, not a minor detail that can be set aside.

The primary endpoint wording highlights a second statistical issue: an outcome described as the number of participants is not necessarily the same as a count of adverse events. Clear specification of the unit matters because participants can have repeated events, and participant-level and event-level summaries answer different questions. The registry record does not clarify this wording or report the endpoint result.

Finally, the record distinguishes safety and efficacy populations but does not report their sizes or analysis methods. Such details help readers understand which observations contribute to each outcome and how missing follow-up is handled. The listed safety counts offer descriptive information, but the missing primary result, uncertainty measures, and analytic details leave important questions unanswered. These features make the record a useful example of why design, endpoint definition, and reporting completeness all shape statistical interpretation.

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 primary endpoint result is not reported in the registry record. As a result, the central endpoint cannot be evaluated for magnitude or precision. The record also does not provide an uncertainty interval or analysis method for that endpoint.

The endpoint title refers to participants with treatment-related adverse events, whereas its description refers to the number of treatment-emergent adverse events considered definitely, probably, or possibly related to treatment. The record does not reconcile the participant-versus-event distinction. That leaves uncertainty about the intended unit of analysis and whether multiple events in one participant were counted separately.

The design is single-group, with no like-for-like control comparison. The record therefore cannot establish a comparative treatment effect. The study cohort was selected from adults who had successfully completed treatment in earlier studies, which limits direct generalization to people outside that selection context.

Although the endpoint timeframe is every two weeks up to 60 months, participant-level follow-up and exposure durations are not reported. The registry also does not describe missing-data handling, the statistical analysis plan, a sample-size justification for the trial, or how multiple outcomes were addressed. The serious-event terms have listed percentages, but their denominator and calculation basis are not reported. The death entry has no reported cause or treatment-relatedness assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Extension Study of PRX-102 for up to 60 Months — NCT01981720.
• Registry record last updated 2023-09-13; status last verified 2023-09.
• Results first posted 2023-02-08.
• 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.

18. Record Summary

NCT01981720 is a completed Phase 1 and Phase 2, single-group extension study sponsored by Protalix. It enrolled 15 adult Fabry patients who had successfully completed PRX-102 treatment in studies PB-102-F01 and PB-102-F02. PRX-102 was administered intravenously at 1.0 mg/kg every 2 weeks, with a permitted window of +/- 3 days, for a stated timeframe of up to 60 months.

The primary endpoint concerns treatment-related adverse events assessed by CTCAE v4.03, but its result and analysis are not reported in the registry record. The safety listing includes serious- and other-event counts, three listed serious-event terms at 6.7% each, and 1 death. The record does not establish that listed events or the death were caused by treatment. There is no comparator group, and the record does not report the statistical methods, uncertainty estimates, or missing-data approach.