A Gene Transfer Therapy Study to Evaluate the Safety of SRP-9004 (Patidistrogene Bexoparvovec) in Participants With Limb-Girdle Muscular Dystrophy, Type 2D (LGMD2D): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Gene Transfer Therapy Study to Evaluate the Safety of SRP-9004 (Patidistrogene Bexoparvovec) in Participants With Limb-Girdle Muscular Dystrophy, Type 2D (LGMD2D) (NCT01976091), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events (AEs)..

2. Clinical Question

The registry describes a Phase I/IIA study with an enrollment of 6. Its stated focus is safety during dose escalation and administration by isolated limb infusion. In a study of this size, event counts can identify events recorded among participants, but they provide limited precision for estimating how frequently an event might occur in a broader population. The absence of a control group also means that these counts cannot by themselves distinguish events associated with study treatment from events that might have occurred for other reasons.

A secondary outcome is change from baseline in the distance walked in 6 minutes (6MWT). Results for that outcome are not reported in the registry record. The primary safety question and the secondary walking measure address different aspects of the study: one records adverse events, while the other measures change in walking distance. Neither registry-listed endpoint, as presented, supplies a randomized comparison.

3. Trial Design

This was a Phase I/IIA, non-randomized, open-label, sequential study of SRP-9004 in participants with LGMD2D. Enrollment was 6. The registry lists a study start of 2015-02-01, primary completion on 2019-03-14, and status as completed. Participants and investigators were not masked, and allocation was not randomized.

The registry describes three cohorts. Cohort 1A was for non-ambulant participants and involved one low dose administered by ILI to a single limb on Day 0. Cohort 1B involved one low dose administered by ILI to both limbs on Day 0. Cohort 2 involved one high dose administered by ILI to both limbs on Day 0. This sequence represents different treatment plans, not randomized treatment groups. The registry does not provide a protocol-level account of how participants were assigned to or progressed through the cohorts.

The primary endpoint was the number of participants with AEs, with a timeframe of up to 2 Years. The registry defines an AE as an untoward medical occurrence associated with use of a drug in humans, whether or not considered related to study drug. Seriousness was based on specified outcomes, including death, life-threatening events, hospitalization, persistent or significant incapacity, substantial disruption of normal life functions, or a congenital anomaly or birth defect. A treatment-related treatment-emergent AE was one classified by the investigator as related to treatment.

The registry also lists change from baseline in 6MWT distance as a secondary outcome. A detailed statistical analysis plan, the rationale for the enrollment target, interim analyses, and a more specific account of cohort progression are not reported in the registry record. The design therefore supports descriptive safety reporting, but not a controlled estimate of comparative benefit or harm.

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: Participants with limb-girdle muscular dystrophy, type 2D (LGMD2D) were enrolled into 3 cohorts: Cohort 1A (non-ambulant adult participants), Cohort 1B (pediatric participants), and Cohort 2 (pediatric participants).

Overall Study

Analysis population for the primary outcome, as defined in the registry: The FAS included all participants who received at least 1 administration of SRP-9004.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The full analysis set (FAS) included all participants who received at least 1 administration of SRP-9004 during the study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AEs)., measured over Up to 2 Years.

The primary endpoint counts participants who experienced an adverse event during follow-up of up to 2 Years. It is a participant-count outcome: it records whether an event was reported for a participant, rather than measuring the duration or severity of every event as a continuous quantity. The registry also provides counts of participants with serious adverse events and other adverse events by cohort.

Safety studies use adverse-event monitoring to document untoward medical occurrences during exposure and follow-up. Recording events whether or not investigators consider them treatment-related helps keep the event definition broad; the count is not itself a judgment about cause. Seriousness is separately defined by consequences such as death, life-threatening events, hospitalization, or significant incapacity. A serious event is not automatically a treatment-related event.

The count is useful for describing what was observed in the enrolled participants and for identifying events that may merit attention in further study. It does not, on its own, estimate the causal effect of treatment. That distinction matters particularly in a non-randomized study without a control group: the registry-recorded counts have no concurrent comparison to show how event occurrence might differ without treatment.

The endpoint also does not summarize changes in walking ability. The 6MWT distance is listed separately as a secondary outcome, and its results are not reported in the registry record. Thus, the primary endpoint answers a safety-reporting question, not an efficacy question.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help clarify what a study can conclude from its design and results. In this study, the key features are a participant-count safety endpoint, small sequential cohorts, no randomization, and no reported inferential analyses. The most appropriate reading is therefore descriptive: the counts identify what was recorded among participants, while leaving uncertainty about underlying event rates and causal effects.

What does a participant count represent?

The primary endpoint counts participants with adverse events. A participant-level count differs from an event count. If one participant has multiple events, that participant is still counted once in a measure of participants affected. Event counts can convey recurrence or burden, but those are not the same quantity and are not reported by these participant counts. The registry also separates serious adverse events from other adverse events, using its stated seriousness criteria.

These counts are directly interpretable for the enrolled cohort: they tell the reader how many participants at risk were recorded as affected. They are not, however, a precise estimate of the probability of an event in a larger population. With small denominators, a change in the experience of one participant can substantially alter the apparent pattern. A confidence interval, when reported, expresses uncertainty around an estimate; wider intervals indicate less precision. Confidence intervals for the primary endpoint are not reported in the registry record.

Why is the design important?

Randomization is a method for making treatment groups more comparable with respect to factors that could influence outcomes. This trial was non-randomized, and the cohorts were sequential. It therefore does not create a randomized control comparison. Participants in different cohorts may differ for reasons other than the treatment plan, and cohort treatment plans also differed in dose and whether one or both limbs were treated. A simple difference in adverse-event counts between cohorts would not isolate the effect of dose or administration approach.

Open-label status means that masking was absent. In safety reporting, awareness of treatment assignment can potentially influence event recognition, reporting, or assessment. This is a general methodological consideration, not evidence that reporting was biased in this study. The registry record does not describe procedures intended to assess or adjust for such effects.

What can an inferential analysis add?

Inferential methods can quantify uncertainty or compare outcomes under specified assumptions. Their interpretation depends on the design, the outcome definition, and the analysis plan. The registry lists 0 analyses. It does not report hypothesis tests, confidence intervals, adjusted estimates, or a statistical analysis plan for the primary outcome. As a result, there is no registry-reported inferential result to interpret. The counts should not be converted into a claim of statistical significance or non-significance.

General statistical methods may also address over-dispersion, which occurs when outcome variability exceeds what a chosen model assumes. This concern can arise for count outcomes, but no model or over-dispersion assessment is reported for this study. The primary endpoint is a count of participants affected, not a reported rate of recurrent events, so conclusions about count-model fit cannot be drawn from the registry entry.

How should planning illustrations be understood?

Sample-size calculations are planning tools, not results observed in a trial. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. For non-time-to-event outcomes, the intended display is participants per arm for a stated power level. These calculations do not change the actual non-randomized design, create a control group, or show that the trial had a particular probability of detecting an effect. Sample sizes for planning are not observed power.

The registry record does not report the trial's own sample-size justification. It would therefore be inappropriate to present a planning calculation as the original enrollment rationale or as evidence that the study was adequately powered for a specific comparison. The small enrollment and absence of a randomized comparator remain central to interpretation regardless of planning assumptions.

What about secondary outcomes?

The 6MWT is listed as a secondary outcome measuring change from baseline in distance walked. A change score requires baseline and follow-up observations and a defined analysis approach. The registry record does not report its result or the analysis method. No direction, magnitude, precision, or significance of change can be inferred from the outcome listing alone.

In general, confidence intervals and model-based estimates can help communicate both the magnitude and uncertainty of an outcome. Their usefulness depends on clear reporting of the population analyzed, missing observations, and analytic assumptions. Those details are not reported in the registry record for the outcomes. The available evidence is consequently best understood as a descriptive record of safety counts, without a reported comparative or model-based estimate.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study makes several statistical comparisons or evaluates multiple outcomes. If each is tested separately, the chance of at least one apparently notable result can increase. The registry lists a primary safety outcome and a secondary 6MWT outcome, but it does not report a multiplicity strategy, a hierarchy of testing, or inferential analyses. It is therefore not possible to determine whether any adjustment was planned or needed for reported tests.

The registry does not report how missing outcome data were handled, how many participants contributed data at each assessment, or whether any imputation or sensitivity analyses were used. These details matter because missing observations can affect interpretation, particularly for a change-from-baseline measure. The registry listing of an outcome does not establish that results were available for every participant.

The primary population is described as the FAS, including all participants who received at least 1 administration of SRP-9004. The registry record does not report the analysis population counts by endpoint or provide further detail on exclusions or analysis procedures. The enrollment of 6 should not automatically be assumed to equal the number analyzed for every outcome.

Interim analyses and a detailed statistical analysis plan are not reported in the registry record. Without those details, the timing and rules for any planned repeated testing cannot be assessed. These omissions do not alter the recorded event counts, but they limit assessment of how outcomes were selected, analyzed, and handled when data were unavailable.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: rhabdomyolysis (50.0%), myoglobinuria (50.0%), femur fracture (33.3%).

The serious adverse-event counts are participant counts by cohort: 0 of 1 in Cohort 1A, 2 of 3 in Cohort 1B, and 1 of 2 in Cohort 2. The registry records 0 deaths in each cohort. These observations describe the enrolled participants and should not be treated as precise estimates for a wider population.

The registry defines seriousness by outcomes that include death, a life-threatening AE, inpatient hospitalization or prolongation of hospitalization, persistent or significant incapacity, substantial disruption of normal life functions, or a congenital anomaly or birth defect. Seriousness and treatment relatedness are different classifications. An AE could meet the seriousness definition without being judged related to treatment; the general AE definition includes occurrences whether or not considered study-drug related.

The listed terms—rhabdomyolysis, myoglobinuria, and femur fracture—are accompanied by percentages, but their denominator and cohort allocation are not reported in the registry record. Those percentages should not be read as treatment-related rates or as comparisons between cohorts. The record does not provide sufficient information in this summary to establish whether each term occurred in a unique participant or how terms overlap.

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

The results establish that adverse events were recorded among participants who received SRP-9004 in this study. The registry provides cohort-specific counts for participants with serious and other adverse events and records no deaths in the cohorts. It also lists several serious-event terms. These are observations from the study, not conclusions about what caused each event.

The counts do not establish that SRP-9004 caused an event, nor do they show how event occurrence would compare with no treatment or another intervention. The study was non-randomized, open-label, and sequential, with no like-for-like control group. Differences between cohorts cannot be attributed to dose or limb administration alone, because the design does not separate these features from other possible differences among participants or cohorts.

The results also do not provide a precise estimate of safety in a broader population. Enrollment was 6, and the cohort counts are small. In general, small samples yield limited precision, so even a clearly recorded count may leave substantial uncertainty about how often an event might occur in other settings. The registry does not report confidence intervals or inferential analyses for the primary endpoint.

The primary endpoint concerns adverse events, not treatment benefit. The registry lists a secondary 6MWT outcome, but its results are not reported in the registry record. No conclusion about change in walking distance or functional benefit follows from the endpoint listing alone. More generally, the completed status of a trial indicates its status in the record; it does not itself establish the direction, magnitude, or certainty of an outcome.

13. Why This Trial Matters Statistically

This trial illustrates how early-phase safety records should be read when enrollment is small and treatment groups are not randomized. Participant counts can document what happened in the enrolled cohorts, but the design limits how far those observations can be generalized or compared. Keeping descriptive findings distinct from causal claims is especially important when there is no concurrent control group.

The cohort structure also makes the distinction between treatment description and treatment comparison visible. The cohorts differed in dose and whether treatment was administered to one limb or both limbs. Because allocation was non-randomized and sequential, observed differences in safety counts do not isolate the contribution of any one feature. This is a design limitation, not a statistical adjustment that can be resolved from the reported counts alone.

Another statistical lesson is that a list of adverse events and participant counts communicates different information. Counts show how many participants were affected, while event terms identify what was recorded. Neither automatically establishes severity beyond the stated classifications, treatment relatedness, or recurrence. Explicit definitions and clear denominators are essential to avoid interpreting percentages as cohort risks when the record does not specify that meaning.

Finally, the registry identifies a secondary functional outcome but does not report its results. Distinguishing an outcome's presence in a protocol record from its reported findings prevents unsupported conclusions about efficacy. The record is useful for understanding the study's design and recorded safety observations, while also showing why complete reporting of analysis methods, missing data, and outcome estimates is important for 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 enrollment of 6 limits the precision and generalizability of the safety counts. Each cohort contains few participants at risk, so the observed counts should be interpreted as descriptions of this study rather than dependable estimates for a wider population. The registry record does not report confidence intervals for these results.

There is no randomized control group. The cohorts are sequential and differ in dose and in whether one or both limbs received treatment. Therefore, comparisons across cohorts are not like-for-like comparisons and cannot isolate the effect of dose, laterality, or administration strategy. The open-label design also means masking was absent; the registry does not report whether event assessment used additional safeguards against reporting or assessment effects.

The serious-event term percentages are listed without a clear denominator or cohort assignment in the registry record. They cannot safely be interpreted as cohort-specific event risks. The record also does not give participant-level event detail, the number of distinct events per participant, or complete information on event timing and treatment relatedness for each term.

Although a secondary 6MWT outcome is listed, its results are not reported in the registry record. A detailed statistical analysis plan, the rationale for the enrollment target, interim analyses, inferential analyses, and methods for missing data are also not reported. These limitations constrain assessment of outcome precision and analytic choices. They do not negate the reported counts, but they restrict the conclusions that can be drawn from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Gene Transfer Therapy Study to Evaluate the Safety of SRP-9004 (Patidistrogene Bexoparvovec) in Participants With Limb-Girdle Muscular Dystrophy, Type 2D (LGMD2D) — NCT01976091.
• Registry record last updated 2023-06-15; status last verified 2023-04.
• Results first posted 2022-04-01.
• 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

NCT01976091 is a completed Phase I/IIA, non-randomized, open-label, sequential gene-transfer study of SRP-9004 in LGMD2D. Enrollment was 6. The study evaluated low-dose treatment to a single limb, low-dose treatment to both limbs, and high-dose treatment to both limbs, administered by isolated limb infusion.

The primary endpoint counted participants with adverse events during follow-up of up to 2 Years. Serious adverse events were recorded in Cohort 1B and Cohort 2, and no deaths were recorded in any cohort. The registry also lists 6MWT change from baseline as a secondary outcome, but its results are not reported in the registry record.

Because the study was small, non-randomized, and had no control group, its safety counts are descriptive and do not establish causation or comparative effects. The registry record does not report inferential analyses, confidence intervals, a detailed statistical analysis plan, or the sample-size justification.