MGTA-456 in Patients With Inherited Metabolic Disorders Undergoing Hematopoietic Stem Cell Transplantation (HSCT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MGTA-456 in Patients With Inherited Metabolic Disorders Undergoing Hematopoietic Stem Cell Transplantation (HSCT) (NCT03406962), a na phase 2 study. The primary outcome is Number of Participants With Engraftment.

2. Clinical Question

The primary endpoint is a participant count, not a comparison of response rates between assigned groups. Engraftment is defined in the registry record as achieving an absolute neutrophil count (ANC) ≥0.5 × 10⁹/L for 3 consecutive days. The clinical question is therefore descriptive: whether, and how often, this threshold was reached during the stated timeframe among the participants who received the investigational product.

The registry record describes the study as designed to assess safety and efficacy, and lists infusion toxicities as a secondary outcome. However, it does not report an observed value for the primary endpoint or an analysis of the secondary outcome. The record also does not report a comparator group, so it cannot directly answer how outcomes would differ under another treatment strategy. Any interpretation of the clinical question must keep that single-group design and the absence of posted outcome analyses in view.

3. Trial Design

This was a phase 2, single-arm, open-label study of MGTA-456 in patients with inherited metabolic disorders undergoing hematopoietic stem cell transplantation. The registry lists one intervention, MGTA-456, and a single group. Allocation is recorded as not applicable, and masking as none. There is no separate randomized or concurrent control group to provide a like-for-like comparison.

The registry reports enrollment of 8 and a completed study status. The recorded start date is 2018-02-09, and the primary completion date is 2020-02-10. These dates describe the study timeline in the registry; they do not supply the timing or duration of individual participant follow-up beyond the primary endpoint timeframe.

The product is described as an expanded CD34+ cell therapy investigational product used in replacement of single umbilical cord blood transplantation. The study description identifies safety and efficacy as its aims. The primary outcome is the number of participants with engraftment within 42 days, while the listed secondary outcome is the number of participants with infusion toxicities.

An open-label design means masking was not used, as recorded in the registry. The registry record does not report further details about outcome assessment procedures or any steps taken to reduce assessment bias. It also does not report a statistical analysis plan, sample-size justification, interim analyses, or a planned statistical comparison. In a single-arm study, participant outcomes can be described, but without a control group the study design alone cannot separate changes associated with the intervention from other explanations. The registry record identifies no like-for-like control comparison.

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: Before an enrolled patient was infused with MGTA-456, the patient had to undergo a protocol-defined conditioning regimen and the proper expansion and manufacture of MGTA-456 investigational cell therapy product was confirmed.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients who received MGTA-456 investigational product

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 Engraftment, measured over 42 days.

The primary endpoint counts participants who achieved engraftment during the specified 42-day timeframe. The registry defines engraftment as achieving an absolute neutrophil count (ANC) ≥0.5 × 10⁹/L for 3 consecutive days. The outcome unit is participants, and the population is patients who received MGTA-456.

A participant count is a binary-outcome summary: each person either meets the stated definition or does not, according to the endpoint rules. This type of endpoint is useful for describing how often a prespecified event occurred in the study population. The definition gives a threshold and a duration, which make the outcome more specific than a general statement that engraftment occurred.

The 42-day timeframe also matters to interpretation. The endpoint concerns achievement within that stated period, not whether engraftment occurred at any later time. The registry record does not report an observed count, an estimate of uncertainty, or participant-level outcome data. It therefore identifies what was intended to be measured but does not allow the observed frequency or its precision to be assessed. The registry record also does not report further details about how endpoint data were collected or handled when unavailable.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary primary outcome: participants either meet the engraftment definition within 42 days or do not. It reports the definition and the population to which it applies, but it lists no outcome analyses. The methods concepts below explain how such results are commonly interpreted in general; they are not descriptions of analyses reported for this study.

What does a participant count tell us?

A count states how many people in the analysed group experienced an event. For a binary endpoint, that count is often accompanied by the group size and, in some settings, a proportion. The count is the direct descriptive result; the proportion puts it in context by relating it to the size of the group. No observed engraftment count or proportion is reported in the registry record, so neither can be stated for this study.

General statistical explanation: a count alone does not describe uncertainty about the frequency that might be expected in a broader population. An interval estimate can convey the range of values reasonably compatible with the observed data under the chosen method. The width of an interval is affected by the amount of information in the data and by the method used. The registry record does not report an interval estimate or the method for calculating one.

Why does the single-arm design matter?

A single-arm study can describe outcomes among participants receiving the intervention, but it does not create a concurrent comparison group. General statistical explanation: a treatment effect is usually a contrast between outcomes under different strategies, and an unobserved counterfactual cannot be recovered merely by measuring one group. Without a comparator, a result cannot directly quantify how the outcome differs from another strategy. The registry itself flags that this is not a randomized comparison and that the arms are not a like-for-like control comparison.

The open-label design means masking was not used. General statistical explanation: when study participants or assessors know which intervention is being given, expectations or awareness can sometimes influence reporting or assessment, depending on the outcome and procedures. The registry record does not describe assessment safeguards, so their presence or absence cannot be assessed from the record.

What do significance tests and confidence intervals contribute?

A significance test evaluates how compatible the observed data are with a specified null hypothesis under stated assumptions. A p-value is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. A confidence interval focuses on the range of values compatible with the data and method, and can communicate precision more directly than a significance label. No p-value, confidence interval, or inferential result for the primary outcome is reported in the registry record.

These concepts do not fill in missing results. Because the record lists no analyses, it would be inappropriate to infer statistical significance, an effect estimate, or a confidence interval from enrollment, endpoint definitions, or safety entries. The registry record does not report an analysis plan specifying a test, interval method, or adjustment strategy.

How should planning illustrations be read?

General statistical explanation: sample-size calculations describe how much information a future study might need under a set of assumptions. They are planning tools, not evidence that a study observed a particular effect or achieved a particular probability of detecting one. The planning assumptions associated with this trial are described as an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated fraction of the observed effect defines the effect the illustration is intended to detect. The record does not report that these were the trial's design assumptions, and the trial itself is single-arm.

For participant-based outcomes, a planning result expressed per arm would concern a hypothetical design with arms; it would not change the actual single-group design or add a comparator to the study. A planning value is not an observed sample size, outcome, or measure of the trial's success. The registry record does not report the study's own sample-size justification or a statistical power calculation used to design the trial.

Why can event distributions complicate analysis?

General statistical explanation: when data are counts of events rather than counts of people with an event, the same person may contribute more than one event. Such counts can vary more than a simple model assumes, a feature called over-dispersion. Methods that allow for over-dispersion can yield more realistic uncertainty when that feature is present. This trial's primary endpoint is a count of participants meeting a binary definition, not a reported recurrent-event analysis. The registry record does not describe a model for the primary endpoint, and no analysis is listed.

In short, methods such as interval estimation, hypothesis testing, and sample-size planning require observed outcome data and clearly stated assumptions. The registry supplies an endpoint definition and design information, but not the reported primary outcome analysis needed to apply those methods to an observed engraftment result.

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("MGTA-456 Cohort 1", "MGTA-456 Cohort 2")
n      <- c(6, 2)
events <- c(6, 2)
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  MGTA-456 Cohort 1  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  MGTA-456 Cohort 2  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, timepoints, groups, or statistical tests are examined. General statistical explanation: as the number of tests increases, the chance of at least one apparently unusual result can increase unless the analysis plan addresses the issue. The registry lists a primary engraftment outcome and a secondary outcome concerning infusion toxicities. It does not report a multiplicity strategy, such as a testing hierarchy or adjustment, and no outcome analyses are listed. It is therefore not possible to determine whether any inferential claims were adjusted for multiple testing.

The registry identifies the primary endpoint timeframe as 42 days. It does not report additional primary timepoints or an analysis plan describing how repeated measurements, if any, would be handled. The registry record also does not report whether interim analyses were planned or conducted. Those details should not be inferred from the phase of the study or its completed status.

Missing data are another important consideration for a participant-count endpoint. General statistical explanation: if endpoint status is unavailable for some participants, the analysed denominator and assumptions about those missing outcomes can affect interpretation. The registry record does not describe missing-data methods, imputation, exclusions, withdrawals, or the number of participants with evaluable primary outcome data. Enrollment is reported as 8, but that alone does not establish how many were included in any outcome analysis.

The record identifies the primary population as patients who received MGTA-456, but it does not report analysis populations or explain whether all enrolled participants received the product. It also does not describe how participants with incomplete follow-up or protocol deviations were treated. Since no analyses are listed, the handling of missing outcomes, multiplicity, and analysis populations is 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: autoimmune hemolytic anemia (37.5%), immune thrombocytopenia (37.5%), pyrexia (37.5%), pneumonia (25.0%), sepsis (25.0%).

The registry adverse-event summary records 8 participants at risk and 8 affected for serious events in the MGTA-456 group. It gives the same at-risk and affected counts for other events. The summary also records 2 deaths. These figures describe what the registry lists; they do not establish the cause of an event or death.

The serious-event terms with recorded percentages are autoimmune hemolytic anemia (37.5%), immune thrombocytopenia (37.5%), pyrexia (37.5%), pneumonia (25.0%), sepsis (25.0%), and staphylococcal bacteremia (25.0%). These are registry entries, not a comparison with an untreated or alternative-treatment group. They should not be read as estimates of excess risk attributable to MGTA-456.

General statistical explanation: safety summaries are descriptive unless a comparative design and analysis support a contrast. Counts and percentages depend on their definitions and denominators; the registry does not give further detail about event timing, recurrence, severity grading, relatedness assessment, or how overlapping events are represented. The listed terms may describe events rather than distinct participants, so they should not be added together to infer a total number of affected people. The record does not report a causal assessment for the deaths or listed events.

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

The record documents a completed, open-label, single-arm phase 2 study of MGTA-456 in patients with inherited metabolic disorders undergoing hematopoietic stem cell transplantation. It specifies the primary endpoint as the number of participants with engraftment within 42 days, using a defined ANC threshold sustained for 3 consecutive days. It also lists infusion toxicities as a secondary outcome and provides descriptive safety entries.

What the registry record does not provide is the observed result for the primary endpoint or an analysis of the secondary outcome. It lists no outcome analyses. Therefore, it does not establish how many participants achieved engraftment, the precision of that result, or a statistical comparison. The completed status and stated enrollment do not substitute for outcome data.

The single-arm design also means the study does not offer a like-for-like control comparison. Even if an observed outcome count were reported, a within-study description would not by itself show how outcomes compare with another treatment strategy. That distinction is central to interpreting efficacy claims. The registry record does not report a statistical analysis plan that could support a comparative claim.

The safety entries identify events and deaths recorded in the registry, but they do not demonstrate that MGTA-456 caused them. There is no comparator group in this record to quantify relative safety, and the record does not provide a causal assessment or additional event-level context. These entries should be treated as descriptive safety information, not as evidence of a treatment effect.

General statistical interpretation: evidence is most informative when the outcome definition, observed estimate, uncertainty, analysis population, and design all align with the question being asked. Here the endpoint definition and study structure are reported, while the numerical outcome analysis is not reported in the registry record. The appropriate conclusion is therefore about what was planned and recorded, rather than about an unreported clinical result.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clear primary endpoint definition and the lack of a reported endpoint analysis in the registry record. Engraftment is defined using a threshold, a consecutive-day requirement, a timeframe, and a specified population. Those details help make the intended measurement interpretable. But without the observed participant count, the central descriptive result cannot be assessed.

The single-arm structure is also consequential. A study can collect useful descriptive information about participants who receive an intervention, but the absence of a control group prevents a direct within-trial comparison. This limitation is not repaired by naming the study as phase 2, by its completed status, or by an outcome definition. Statistical conclusions must match the design.

The reported enrollment of 8 makes transparent reporting especially important: readers need the observed outcome count and the number of participants included in the analysis to understand the evidence. The record does not report those outcome-analysis details. Nor does it report an uncertainty estimate, a statistical plan, or the approach to missing outcomes. Without these items, readers cannot judge the precision or analytic robustness of the primary result.

The safety information likewise illustrates the difference between listing events and making a causal or comparative inference. Serious-event terms, percentages, affected counts, and deaths are important descriptive entries, but they do not show whether event frequency differs from another strategy or whether events were caused by the intervention.

General statistical lesson: transparent endpoint definitions are necessary, but they are not enough. Interpretation also depends on complete results, denominators, uncertainty, analysis choices, and a design suited to the intended comparison. The registry record makes some design and safety details visible while leaving the primary outcome analysis unreported.

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 main trial-specific limitation for statistical interpretation is that the registry record lists no outcome analyses. Although the primary endpoint is defined and the study is marked completed, the observed number of participants with engraftment is not reported in the registry record. There is consequently no estimate or interval from which to assess the endpoint's observed frequency or precision.

The study has a single-group design with no like-for-like control comparison. This limits causal and comparative interpretation, even if descriptive results are available elsewhere. The registry record reports enrollment of 8, but does not report the number included in a primary outcome analysis or whether all enrolled participants received MGTA-456.

Other analysis details are also not reported in the registry record: missing-data handling, analysis populations, a statistical analysis plan, multiplicity procedures, interim analyses, and the study's sample-size justification. The record does not explain whether endpoint assessments were masked or how assessment procedures were implemented. No assumptions about these methods can be made from the open-label designation alone.

The safety summary gives participant counts, serious-event terms, percentages, and deaths, but does not provide further context about event timing, recurrence, relatedness, or causal assessment. The registry record also does not supply a control group for a safety comparison. These limitations mean the safety entries should be interpreted descriptively and not as comparative or causal estimates.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: MGTA-456 in Patients With Inherited Metabolic Disorders Undergoing Hematopoietic Stem Cell Transplantation (HSCT) — NCT03406962.
• Registry record last updated 2021-11-03; status last verified 2020-06.
• Results first posted 2021-10-28.
• 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

The registry describes NCT03406962 as a completed phase 2, single-arm, open-label study of MGTA-456 in patients with inherited metabolic disorders undergoing hematopoietic stem cell transplantation. Enrollment is reported as 8. The study start date is 2018-02-09, and the primary completion date is 2020-02-10.

The primary endpoint is the number of participants with engraftment within 42 days, defined as ANC ≥0.5 × 10⁹/L for 3 consecutive days. Infusion toxicities are listed as a secondary outcome. The registry reports safety entries, including 2 deaths and several serious-event terms with percentages, but gives no causal assessment. No outcome analyses are listed, and the observed primary endpoint result is not reported in the registry record.