A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD) (NCT01896102), a na phase 2, phase 3 study. The primary outcome is Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 and Without Allo-HSCT or Rescue Cell Administration.

2. Clinical Question

3. Trial Design

This completed phase 2/3 study evaluated autologous hematopoietic stem cells transduced with Lenti-D lentiviral vector in participants with cerebral adrenoleukodystrophy. The registry lists an enrollment of 32 and a single-group model. Participants received one intravenous infusion of Lenti-D drug product; the arm description specifies a dose of at least 5.0 × 10^6 CD34+ cells per kilogram. The registry summary describes collection and modification of participants’ own blood stem cells, followed by transplantation after myeloablative conditioning.

Because there was no separate control arm, the study design does not estimate a treatment contrast against a concurrent comparator. The endpoint is a proportion within the treated group, rather than a difference between groups. The record lists masking as none. It does not report a randomized allocation or a like-for-like control comparison.

The study was listed as phase 2/3 and is marked completed. The primary endpoint was assessed at Month 24. The registry lists other outcomes, including imaging findings, neurological function, disability-free and overall survival, and engraftment measures. Participants were to be followed continuously in study LTF-304, according to the brief summary. How that follow-up was incorporated into the posted endpoint analyses is not reported in the registry record.

The posted enrollment describes the study size, not the number of participants contributing to every endpoint. The primary endpoint definition distinguishes the Transplant Population from participants evaluable at Month 24. The record’s available population description is incomplete, so the exact endpoint denominator and the handling of participants without a Month 24 assessment 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 32 Participants were enrolled and treated in this study. All male participants with Cerebral Adrenoleukodystrophy (CALD) were treated with Lenti-D Drug Product also referred to as eli-cel (elivaldogene autotemcel) in this study. For study ALD-102 the Transplant Population (TP), Neutrophil Engraftment Population (NEP), and Intent-to-Treat Population (ITT) are identical.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Transplant Population (TP) consisted of participants who received Lenti-D Drug Product infusion. Evaluable participants were defined as those who had been followed for 24 months (i.e. Rel DLC \>= 730) or have had completed Month 24, or discontinued from the study but would have been followed for 24 months if still on the study (i.e. Rel Day of data cut \>= 730).

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 Intent-to-treat Population (ITT) consisted of participants who initiated any study procedures, beginning with mobilization by granulocyte colony-stimulating factor (G-CSF).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 and Without Allo-HSCT or Rescue Cell Administration, measured over At Month 24.

The primary endpoint is the percentage of participants who, at Month 24, were alive and had none of the six major functional disabilities (MFDs), without allogeneic hematopoietic stem cell transplantation or rescue cell administration. The listed disabilities are loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, and complete loss of voluntary movement. The endpoint criteria also require that participants had not withdrawn from the study and had not been lost to follow-up by Month 24.

This is a composite endpoint: a participant must meet several conditions at the same time to count as meeting the endpoint. It combines survival, functional status, receipt of rescue treatment or transplantation, and follow-up status. Such a composite can represent a clinically meaningful overall state, but its interpretation depends on each component and on the rules used for incomplete follow-up. The registry record does not report separate primary-endpoint results for the individual components.

The registry specifies a percentage and a 95% confidence interval as the endpoint summary. A confidence interval describes the statistical uncertainty around an estimate; it does not resolve the limitations of a single-group design or supply a comparison with another treatment. A numerical percentage or confidence interval for this primary endpoint is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is expressed as a percentage of participants, a natural summary for a binary endpoint. Each participant either meets the full Month 24 definition or does not. The registry specifies a 95% confidence interval for this percentage. In general, a confidence interval communicates the uncertainty associated with an estimated proportion; it is not a guarantee that the true value lies within the interval, and it does not address bias from study design or incomplete outcome ascertainment. The actual estimate and interval are not reported in the registry record.

What does a single-group estimate describe?

In a single-group study, the outcome percentage describes the enrolled and analyzed group under the stated endpoint definition. There is no randomized comparison in this trial. Randomization, in general, can help balance measured and unmeasured factors between groups, while a concurrent control group can provide a direct reference for a treatment contrast. Without those features, an observed percentage cannot be interpreted as the difference attributable to treatment. It may still describe the outcomes recorded for the study group, but causal interpretation requires caution.

The trial is marked as unmasked. In general, knowledge of treatment assignment can influence care, outcome assessment, reporting, or follow-up, depending on the outcome and trial procedures. The registry does not report enough detail to determine whether endpoint assessment was independently reviewed or what safeguards were used. Such procedures are not reported in the registry record.

How should the composite endpoint be understood?

The primary measure requires participants to satisfy several criteria together: being alive at the stated assessment, having none of the listed MFDs, not receiving rescue cell administration or allogeneic transplantation, and not withdrawing or being lost to follow-up by the specified time. This construction can capture an overall state of interest, but it can obscure differences among components. For example, the overall result alone would not reveal whether a classification was driven by disability, survival, rescue treatment, or follow-up status. Separate primary component estimates are not reported in the registry record.

Composite endpoints also rely on prespecified operational definitions. The record gives the listed MFDs and several endpoint conditions, but does not report a complete statistical analysis plan. It is therefore not possible to verify from the registry record how all boundary cases, assessment windows, or incomplete observations were handled.

What do analysis populations contribute?

The registry defines the Transplant Population as participants who received the product infusion. It also refers to evaluable participants in connection with follow-up through Month 24 or completion of that assessment, but the available description ends before the definition is complete. The number included in the primary endpoint analysis and the exact denominator are not reported in the registry record. Distinguishing an enrolled group, a treated group, and an endpoint-evaluable group matters because exclusions or missing assessments can change the population represented by an estimate.

In general, a report should state the analysis population, the number assessed, and how participants without the required outcome information were treated. The primary endpoint includes withdrawal and loss to follow-up among its criteria, so the rule for such cases is central to interpretation. The record does not describe a missing-data method, sensitivity analysis, or participant-level disposition for this endpoint.

What can planning illustrations tell readers?

Sample-size calculations are planning tools: they describe the sample size that would be needed under stated assumptions for a future or hypothetical design. They do not measure the probability that the completed trial detected an effect, and they are not observed power. The planning assumptions recorded for this study describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of an observed effect. Those assumptions describe a hypothetical two-arm planning framework, not the single-group design of this trial. Any such illustration must not be read as the trial’s original design justification or as evidence that the completed study had a particular power. The registry does not report the trial’s own sample-size justification.

For binary outcomes, planning calculations generally depend on the expected event proportions in the groups, the effect to detect, the significance level, and the desired power. If the expected effect is uncertain, planning results can vary substantially. The registry record does not report the original assumptions or justification used to choose the enrollment. No numerical planning result should be interpreted as an observed clinical outcome.

What is missing from the reported statistical plan?

The record lists zero analysis records and does not report a statistical analysis plan. That does not establish that no analyses were conducted; it means the registry record does not present those analysis details in the available record. The method used to calculate the primary confidence interval, any adjustment, prespecified subgroup analyses, interim analyses, and multiplicity procedures are not reported in the registry record. Statistical methods and analysis choices affect how estimates should be interpreted, so the absence of those details limits independent assessment.

Several secondary outcomes are listed, but the record does not specify how results across multiple outcomes were controlled or prioritized. In general, testing many outcomes increases the chance of at least one apparently notable finding unless a suitable strategy is specified. That general concern does not establish that any particular finding is false; it explains why a prespecified multiplicity approach is useful. Without reported analyses or results, no multiplicity-adjusted inference can be assessed.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Lenti-D Drug Product")
n      <- c(32)
events <- c(29)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Lenti-D Drug Product  32  29  90.6  75.0  98.0  75.8  96.8  75.7  96.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and multiple secondary outcomes, including imaging, neurological function, survival, and engraftment measures. It does not report a statistical analysis plan describing how these outcomes were prioritized or whether multiplicity was addressed. In general, examining multiple outcomes can increase the chance of at least one apparently notable result. Prespecified testing sequences, adjustment procedures, or a clear distinction between confirmatory and exploratory outcomes can help readers interpret that risk. None of those procedures is reported in the registry record, so no claim about multiplicity control is justified.

The endpoint definition includes not withdrawing from the study and not being lost to follow-up by Month 24. However, the record does not report how participants with missing assessments were classified, whether missingness was imputed, or whether sensitivity analyses were conducted. These choices can affect a percentage estimate, especially when the endpoint requires complete information about several conditions. It is also not reported how the primary endpoint denominator was determined.

The record defines the Transplant Population as participants who received an infusion and describes an evaluable group in relation to Month 24 follow-up, but the latter definition is incomplete in the registry record. The analyzed population, numbers excluded, and reasons for exclusion are not reported. Interim analyses, monitoring rules, and the trial’s sample-size justification are also not reported in the registry record. These omissions limit assessment of the analysis process; they do not establish that an analysis or procedure was absent from the trial itself.

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: febrile neutropenia (25.0%), pyrexia (18.8%), vascular device infection (9.4%), adrenal insufficiency (6.2%), cardio-respiratory arrest (3.1%).

The registry safety summary lists 32 participants at risk for serious adverse events and 21 affected, and 32 participants at risk for other adverse events and 32 affected. These are participant-level summary figures as recorded; the registry does not provide event-level detail sufficient to determine how many events each participant experienced. The groups can overlap, so the summaries should not be added together.

Selected serious adverse event terms include febrile neutropenia at 25.0%, pyrexia at 18.8%, vascular device infection at 9.4%, adrenal insufficiency at 6.2%, cardio-respiratory arrest at 3.1%, and abdominal pain at 3.1%. These percentages describe the listed terms in this study group; they do not establish that the study product caused the events. The registry lists one death, but cause, timing, and treatment relationship are not reported in the registry record.

Serious adverse events are a safety classification, while “other adverse events” is a separate summary category in the record. The figures do not provide a comparative risk estimate because there was no control group. Follow-up duration and the detailed event collection rules for these summaries are not reported in the registry record. Safety interpretation should therefore remain descriptive and should not treat event proportions as proof of causation or as a comparison with another treatment.

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

The registry record describes a completed single-group study of autologous Lenti-D-transduced hematopoietic stem cells for CALD. It defines a Month 24 primary endpoint that combines survival, absence of six MFDs, no rescue cell administration or allogeneic transplantation, and continued follow-up under the stated criteria. It also reports selected safety summaries and lists additional outcomes.

The primary endpoint’s numerical result and 95% confidence interval are not reported in the registry record. Consequently, the record does not establish the observed proportion meeting the endpoint or the precision of that proportion. It also does not provide a concurrent control comparison. The design cannot, on its own, quantify how outcomes would have differed under another treatment or without the study intervention.

The endpoint is a composite, so even a reported overall percentage would not by itself explain which component determined the result. Component-level primary results are not reported. The incomplete description of the evaluable population and the absence of a stated missing-data method further limit interpretation of who contributed to the endpoint and how incomplete follow-up was handled.

The safety counts and selected event-term percentages indicate what the registry lists for participants in the study group. They do not show whether events were caused by the intervention or whether risks differed from those under another approach. The cause and relationship of the listed death are not reported in the registry record.

Thus, the available record supports an explanation of the study design, outcome definition, and selected safety reporting, but not a conclusion about the size or precision of the primary outcome or a comparative treatment effect. This distinction is important: absence of a posted numerical primary result is not evidence that the endpoint was or was not met. It means the registry record does not report that result.

14. Why This Trial Matters Statistically

This study raises several statistical issues that are important when reading clinical research. Its single-group design makes the distinction between describing outcomes and estimating a treatment effect especially important. A proportion among participants who received an intervention is a descriptive result; without a concurrent comparison group, it does not directly quantify what would have happened under an alternative. The registry identifies this design clearly, so the limits of causal comparison should shape interpretation from the outset.

The primary endpoint is also a composite rather than a single event. It combines survival, multiple functional disabilities, rescue treatment or transplantation, and follow-up status. A composite may bring several important aspects of outcome into one measure, but its overall result can conceal variation among components. Understanding the component definitions and their separate results is therefore valuable; component-specific primary results are not reported in the registry record.

Follow-up rules are central because withdrawal and loss to follow-up appear in the endpoint criteria. A reported percentage would need to be read alongside the denominator, the evaluable-population definition, and the handling of missing information. The registry record does not report the complete evaluable-population definition, the endpoint denominator, or a missing-data method. These are not minor technical details: they determine which participants the estimate represents.

Finally, the record includes multiple secondary outcomes but does not report a statistical analysis plan or multiplicity approach. Clear reporting of endpoint hierarchy, analysis populations, missing-data procedures, and statistical methods allows readers to distinguish prespecified inference from exploratory description. In this record, those details and the numerical primary outcome are not reported, so the statistical interpretation must remain bounded by what is documented.

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 most consequential limitation for interpreting the posted results is that the numerical primary endpoint estimate and its 95% confidence interval are not reported in the registry record. Without them, the endpoint’s observed level and statistical precision cannot be described. The record also lists no analysis records, and the statistical analysis plan is not reported; this prevents assessment of the actual estimation method, any adjustments, or other prespecified analyses.

The single-group design has no concurrent control arm. Any outcome proportion would describe the study group, not a randomized contrast. The registry marks the study as unmasked and does not report details of endpoint assessment or any independent review procedures. These design features limit the kinds of comparisons that can be made from the record, without indicating what the unreported results would have been.

The Month 24 endpoint is a composite and includes follow-up status as well as clinical criteria. The record does not report primary results by component, the exact analyzed denominator, or a complete definition of the evaluable population. It also does not report missing-data handling, sensitivity analyses, or participant disposition for the primary endpoint. The extent and consequences of incomplete follow-up therefore cannot be assessed.

The safety summary provides participant counts and selected event-term percentages, but the record does not report a comparator, detailed event-level data, the duration of safety observation for these summaries, or the cause and treatment relationship of the listed death. These limitations constrain comparisons and causal interpretation. The registry also does not report the trial’s sample-size justification, interim analyses, or multiplicity procedures. These details should not be inferred from the study’s phase designation or enrollment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD) — NCT01896102.
• Registry record last updated 2022-04-25; status last verified 2022-03.
• Results first posted 2022-04-25.
• 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

NCT01896102 is a completed phase 2/3, single-group study of Lenti-D drug product for cerebral adrenoleukodystrophy. The registry lists 32 participants enrolled and describes autologous CD34+ hematopoietic stem cells transduced with Lenti-D lentiviral vector and infused after myeloablative conditioning.

The primary endpoint was the percentage of participants alive at Month 24 without any of six MFDs, rescue cell administration, or allogeneic hematopoietic stem cell transplantation, with withdrawal and loss to follow-up also included in the endpoint criteria. A numerical primary result and its 95% confidence interval are not reported in the registry record.

The record lists multiple secondary outcomes and selected safety summaries. It does not report a statistical analysis plan, a complete evaluable-population definition, missing-data methods, or a concurrent control comparison. The posted information therefore supports description of the design and endpoint, but not a numerical primary-outcome interpretation or comparative treatment-effect estimate.