NAD+ Precursor Supplementation in Friedreich's Ataxia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for NAD+ Precursor Supplementation in Friedreich's Ataxia (NCT04817111), a na phase 2 study. The primary outcome is Percentage of Individuals With Treatment-emergent Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 5.0..

2. Clinical Question

The population description sets the clinical context for interpreting the study: it concerns adults with Friedreich's Ataxia who do not have overt heart failure and meet the stated ejection-fraction criterion. The primary objective was not framed as a comparison of MIB-626 with another treatment. Instead, the study monitored participants receiving MIB-626 and recorded safety outcomes.

The registry record also lists cardiac phosphocreatine/adenosine triphosphate ratio, post-exercise creatine MRI, grip strength, and whole-blood NAD+ concentration as secondary outcomes. These measures address biological or functional questions beyond adverse events. Their inclusion does not establish that changes occurred, and numerical results for them are not reported in the registry record.

3. Trial Design

This was a Phase 2a study of MIB-626 in Friedreich's Ataxia. The registry record classifies the design as single group, with an open-label intervention and no masking. Allocation is recorded as not applicable. The record lists 7 participants enrolled and identifies MIB-626 as the sole intervention; it does not describe a control arm.

The study is listed as completed. Its recorded start date is 2021-05-17 and its primary completion date is 2022-05-19. Those dates describe the registry milestones; they do not, by themselves, establish how long each participant received treatment or remained under observation. The primary outcome timeframe is 14 Days.

The stated primary objective was to assess safety and tolerability of short-term therapy. Safety monitoring included laboratory assessments—CBC, a complete metabolic profile, lipid profile, and HbA1c—along with heart rate, blood pressure, ECG, and standardized symptom assessment. The primary outcome description focuses on the proportion of participants with at least one treatment-emergent adverse event of Grade 1 or higher.

Secondary outcomes listed in the record include cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy for the phosphocreatine/adenosine triphosphate ratio, post-exercise creatine chemical exchange saturation transfer MRI, grip strength, and whole-blood NAD+ concentration. The registry record names Metro International Biotech, LLC as sponsor. Details of treatment schedule, eligibility criteria beyond those summarized in the study description, and analysis procedures are not reported in the registry record.

Because the study has no separate comparator group, its design supports descriptive reporting of outcomes among participants who received MIB-626. It does not provide a concurrent control-based estimate of how outcomes would have differed without the intervention.

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.

Overall Study

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 Percentage of Individuals With Treatment-emergent Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 5.0., measured over 14 Days.

The primary endpoint is the proportion of participants who experienced at least one treatment-emergent adverse event of Grade 1 or higher, assessed using Common Terminology Criteria for Adverse Events Version 5.0. Its timeframe is 14 Days. The endpoint is a participant-level count: each participant is classified according to whether an event meeting the definition was recorded, rather than counting every event as a separate participant.

Safety monitoring also included laboratory results, vital signs, ECG, and standardized symptom assessment. These sources can help identify clinically relevant abnormalities and symptoms during treatment. The registry description says that findings were reviewed for clinical relevance, but details of adjudication or coding procedures are not reported in the registry record.

Adverse-event endpoints are used in early-phase studies to describe the types and frequency of harms observed during exposure. In general, a participant-level outcome gives a clear summary of how many people experienced at least one event, but it does not convey event duration, recurrence, severity beyond the specified threshold, or whether an event was caused by treatment. Those details require additional reporting. The posted adverse-event summary lists 4 participants with other adverse events and 0 with serious adverse events among 7 at risk; those categories should not be treated as a complete account of every endpoint detail.

The primary endpoint is about safety, not efficacy. The listed secondary outcomes address biological and functional measures, but their numerical results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either had at least one qualifying treatment-emergent adverse event during the stated timeframe or did not. For this kind of outcome, a count of participants with an event and the number assessed are the basic descriptive quantities. The registry adverse-event summary lists 4 participants with other adverse events among 7 at risk, and 0 with serious adverse events. It also lists 0 deaths. These counts are not event rates per unit of time and do not tell how many separate events each participant experienced.

What a proportion describes

In general, a proportion expresses the share of the assessed group meeting a defined outcome. It is a summary of the observed group, not a guarantee of the underlying frequency in a wider population. Its precision depends in part on how much information the study contains. With a small group, each participant's outcome has a substantial influence on the summary, so estimates can vary considerably across similar studies. No confidence interval for the primary endpoint is reported in the registry record.

In general, a confidence interval gives a range of values compatible with the data under a specified statistical method. It communicates uncertainty around an estimate; it does not remove the limitations of the design or establish that the interval contains the true value with certainty. Because no interval is reported for this endpoint, the precision cannot be judged using that tool. No hypothesis test or p-value for the primary endpoint is reported in the registry record.

Why the design matters

This study is single group and open label. In general, a control group can provide a basis for comparing outcomes under different study conditions, while masking can reduce some influences on how outcomes are assessed or reported. Neither a control group nor masking is part of the listed design. The findings therefore summarize observations among participants receiving MIB-626, without a within-trial estimate of a difference between treatment groups.

Safety outcomes can be affected by how events are elicited, coded, graded, and attributed. The study description says symptoms were assessed in a standardized way and that laboratory assessments, vital signs, and ECG were reviewed for clinically relevant abnormalities. Specific coding rules, event adjudication, and the handling of events with uncertain attribution are not reported in the registry record. The event counts should be interpreted in light of that reporting limit.

What the analysis plan can establish

The registry record lists 5 outcome measures and 3 analyses, but the specific statistical methods, analysis populations, and mapping of analyses to outcomes are not reported in the registry record. It is therefore not possible to identify whether the posted adverse-event summary is based on all enrolled participants, a defined safety population, or another analysis set beyond the at-risk count shown. No model-based adjustment or inferential procedure is described.

In general, methods for binary outcomes may report counts, proportions, or interval estimates. Choice of method matters particularly when a group is small, because some approximations can be unreliable when counts are sparse. The method used for any interval or test is not reported in the registry record, and no such result should be inferred from the counts alone.

How to read planning illustrations

The registry's sample-size assumptions describe a planning illustration based on an observed effect, not the design used for this study. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event calculations, the convention is a total number of events; for other calculations, the convention is participants per arm.

These assumptions do not turn this single-group study into a randomized two-arm comparison. The record does not report that these assumptions were used to plan the study, nor does it report a sample-size justification for the actual design. Any sample-size values based on such assumptions would be planning illustrations, not observed power and not evidence that the study was adequately sized to answer its safety question.

In general, power is a design-stage probability of detecting a specified effect under stated assumptions. It is not a measure of the probability that a finding is true, and calculating power after observing results does not make an imprecise estimate more informative. The trial's own power calculation, if any, is not reported in the registry record.

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("Open Label - MIB-626")
n      <- c(7)
events <- c(4)
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  Open Label - MIB-626  7  4  57.1  18.4  90.1  25.0  84.2  24.5  84.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 5 outcome measures: the primary safety outcome and secondary measures covering cardiac phosphocreatine/adenosine triphosphate ratio, post-exercise creatine MRI, grip strength, and whole-blood NAD+ concentration. It also lists 3 analyses. The specific analysis assigned to each measure, the order of testing, and any plan to control for multiple comparisons are not reported in the registry record.

In general, when several outcomes are examined, the chance of at least one apparently notable result can increase if each is tested separately without adjustment. A prespecified hierarchy or multiplicity procedure can help clarify how to interpret several statistical tests. No such procedure is reported, and numerical results for the secondary measures are not reported in the registry record. Accordingly, no claim about secondary-outcome differences or statistical significance can be made from the listed measures alone.

Missing-data handling is also not reported in the registry record. The record does not describe whether any outcome observations were missing, how missing observations were handled, or whether analyses used all enrolled participants. The adverse-event summary identifies 7 participants at risk, but that alone does not specify analysis populations for the other outcomes.

In general, missing-data methods and analysis-population definitions matter because they determine which observations contribute to an estimate and what assumptions are needed when outcomes are unavailable. With no reported details, it is not possible to evaluate those aspects for the secondary outcomes or to determine whether any sensitivity analyses were performed. The registry record does not report a protocol-level statistical analysis plan or interim-analysis procedures.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event summary lists 0 affected participants among 7 at risk, and the death count is 0. The same summary lists 4 participants with other adverse events. These are participant counts, not counts of event episodes, and the categories should be read separately. The record does not list any top serious adverse-event terms.

Zero serious events in this group means that none were recorded in the registry's serious-event count for these participants. It does not establish that serious events could not occur, or that the risk is absent in a broader population. The small group size limits how much can be inferred about uncommon events.

Seriousness is not the same as severity. The primary endpoint uses a Grade 1-or-higher severity threshold, whereas the adverse-event summary separates serious events from other events. Thus, the serious-event count alone does not describe the grades of the other events. The registry record does not report their specific terms, grades, timing, duration, or clinical consequences in the registry record for this analysis. These figures are a concise safety summary, not a substitute for detailed event-level reporting.

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

The result describes safety observations in a completed, open-label study of MIB-626 involving 7 participants. The registry adverse-event summary records 4 participants with other adverse events, 0 with serious adverse events, and 0 deaths. Those counts are relevant to the study's stated short-term safety objective, but they are limited to the participants and observation described in the record.

The findings do not establish that MIB-626 caused or prevented any particular event. Without a comparator group, there is no concurrent reference for how often similar events would have occurred in the absence of the intervention. Open-label assessment may also affect how symptoms are reported or evaluated; the record does not describe masking or a blinded assessment process.

These safety counts do not answer whether MIB-626 changes cardiac or skeletal-muscle bioenergetics, grip strength, or whole-blood NAD+ concentration. Those measures are listed as secondary outcomes, but their numerical results are not reported in the registry record. Nor do the safety counts establish effects on disease progression or other outcomes not listed in the study description.

In general, an absence of observed serious events in a small group is not proof that a treatment has no serious risks. Likewise, an observed event does not by itself establish that treatment caused it. The record's counts should be understood as descriptive observations with limited precision, not as a definitive estimate of risk or as a comparative treatment effect.

The study therefore contributes a small, short-term safety description for the population described in the registry. Broader conclusions would require evidence beyond these single-group counts, including fuller outcome reporting and an appropriate design for the question being asked. No medical conclusion about an individual's care follows from this record alone.

14. Why This Trial Matters Statistically

This study illustrates why design and precision matter when interpreting early-phase clinical results. A single-group study can document what happened among participants receiving an intervention, but it cannot provide a randomized comparison with a separate control group. That distinction is central when moving from a descriptive count to a claim about whether outcomes differ because of treatment.

The small enrollment of 7 also makes the limits of event counts visible. Each participant represents a substantial part of the observed group, and the counts provide limited information about less common outcomes. A zero count for serious events is useful to report, but it should not be interpreted as evidence that such events are impossible or absent in a wider population.

The record also makes clear that safety is not captured by a single label. Its primary endpoint concerns treatment-emergent events at Grade 1 or higher, while the adverse-event summary separates serious events from other events. These classifications address different aspects of safety. Complete interpretation would benefit from event descriptions, grading, timing, and analysis details, none of which are reported in the registry record.

Finally, the listed secondary outcomes show the breadth of the biological and functional questions alongside the safety objective. However, listing outcomes is not the same as reporting their findings. Clear reporting of results, analysis populations, missing-data handling, and multiplicity methods is important for assessing how strongly any conclusion is supported. The available record allows a bounded reading of the safety counts, while leaving those other questions unresolved.

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 is its single-group design. With no separate comparator, the observed safety counts cannot estimate a treatment-versus-control difference or separate intervention-related events from background events. The open-label design also means that participants and assessors were not masked, according to the registry record.

Enrollment was 7 participants. This is a limited basis for characterizing safety, particularly for uncommon events, and the registry record does not report a confidence interval for the primary endpoint. The primary outcome timeframe is 14 Days; the record does not establish from that timeframe how long participants were treated or how long other outcomes were followed.

The adverse-event summary provides counts but not detailed event terms, grades, onset, duration, or attribution for the other adverse events. The record lists 0 serious events and 0 deaths, but those counts do not describe the severity distribution among other events. Numerical results for the listed secondary outcomes are not reported in the registry record.

Several analysis details are also not reported in the registry record, including the statistical methods for the primary endpoint, the analysis populations, missing-data handling, multiplicity procedures, and whether any interim analyses occurred. The record does not report the trial's sample-size justification. Without those details, the precision and completeness of the analyses cannot be fully evaluated. These limitations are specific to the information and design described in the registry record and should constrain interpretation of the findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: NAD+ Precursor Supplementation in Friedreich's Ataxia — NCT04817111.
• Registry record last updated 2023-07-17; status last verified 2023-07.
• Results first posted 2023-07-17.
• 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 record describes NCT04817111, “NAD+ Precursor Supplementation in Friedreich's Ataxia,” an open-label Phase 2a, single-group study sponsored by Metro International Biotech, LLC. The study is listed as completed, with 7 participants enrolled. Its recorded start date is 2021-05-17 and its primary completion date is 2022-05-19.

The intervention was MIB-626. The stated primary objective was short-term safety and tolerability in adults with Friedreich's Ataxia without overt heart failure and with a left ventricular ejection fraction at least 40%. The primary outcome was the proportion with at least one treatment-emergent adverse event of Grade 1 or higher during 14 Days. The adverse-event summary lists 4 participants with other adverse events, 0 with serious adverse events, and 0 deaths among 7 at risk. Secondary outcomes included cardiac and skeletal-muscle measures; their numerical results are not reported in the registry record.