An Open Label Phase 2 Study of ManNAc in Subjects With GNE Myopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open Label Phase 2 Study of ManNAc in Subjects With GNE Myopathy (NCT02346461), a non-randomized phase 2 study. The primary outcome is Mean Area Under the Curve (AUClast) of Plasma ManNAc (Baseline-adjusted).

2. Clinical Question

3. Trial Design

This was an open-label Phase 2 study of ManNAc in subjects with GNE myopathy. The registry identifies the allocation as nonrandomized, the masking as none, and the model as single group. It lists enrollment of 12 and describes two dose cohorts. Because allocation was not randomized and no control group is described, the cohorts should not be treated as comparable treatment and control arms.

Cohort A received oral ManNAc 3 g twice daily for 7 days. If safe, subjects in that cohort continued on 6 g twice daily for the remainder of the study. Cohort B received oral ManNAc 6 g twice daily for the duration of the study. The registry therefore describes both an initial dosing period and later exposure, but it does not report the individual treatment histories or explain how subjects were assigned to cohorts.

The study began on 2015-02-05, reached primary completion on 2017-12-30, and is listed as completed. Its primary endpoint was measured at Day 7 and concerned plasma ManNAc exposure. The registry lists 7 outcome measures and no analyses. Numerical results for the primary endpoint, its dispersion, and other outcome measures are not reported in the registry record.

The registry’s safety listings use exposure categories with different time descriptions: ManNAc 3 g - 7 Days, ManNAc 6 g - 7 Days, and ManNAc 6 g - Day 8 to 30 Months. The listed at-risk counts and adverse-event counts belong to those categories; they should not be combined or interpreted as independent randomized groups. The record does not explain whether or how participants appear across more than one exposure category.

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

Analysis population for the primary outcome, as defined in the registry: All subjects received ManNAc

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 Mean Area Under the Curve (AUClast) of Plasma ManNAc (Baseline-adjusted), measured over Day 7.

The primary endpoint is the mean area under the curve (AUC) of plasma ManNAc concentration from time 0, described as dosing, to the last quantifiable concentration. The measurement is baseline-adjusted and specified at Day 7, with units of hr*ng/mL. AUC summarizes concentration over a period of time rather than describing a concentration at just one sampling moment. It is commonly used in pharmacokinetics to characterize systemic exposure to a drug.

The registry names the endpoint as a mean and identifies standard deviation as its dispersion measure. The mean describes the central value of the measured AUCs, while the standard deviation describes how much individual measurements vary around that mean. Baseline adjustment indicates that the endpoint accounts for baseline measurement, but the precise adjustment procedure is not reported in the registry record.

This endpoint addresses plasma exposure, not muscle function, walking ability, or disease progression. Although the registry summary describes a biological rationale involving sialic acid and muscle proteins, that rationale does not make a pharmacokinetic measure a direct measure of clinical benefit. The numerical endpoint result, standard deviation, and any confidence interval are not reported in the registry record, so the magnitude and precision of the observed plasma exposure cannot be assessed from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a mean of a continuous measure: baseline-adjusted AUC of plasma ManNAc at Day 7, in hr*ng/mL. A continuous outcome can take values across a measurement scale rather than being limited to categories such as event or no event. A mean provides a summary of the central level of the measured values; a standard deviation describes their spread around that mean. These summaries answer different questions: the mean concerns the average level, while the standard deviation concerns variability across measurements.

The AUC is defined as the area under the concentration-versus-time curve from time 0 (dosing) to the last quantifiable concentration. In general, an area-under-the-curve measure combines concentration and time, and can summarize exposure across a measurement interval. The exact sampling schedule, calculation method, and handling of values below quantification are not reported in the registry record. The endpoint is described as baseline-adjusted, but the adjustment method is not reported in the registry record either.

In general, a confidence interval expresses uncertainty around an estimate: it gives a range of values compatible with the data under the method used. Its width depends on the amount and variability of the data and the analysis method. No confidence interval for the primary endpoint is reported in the registry record, so the precision of the mean cannot be assessed. Likewise, the record does not report a test statistic or p-value for the primary endpoint.

The trial is listed as nonrandomized, unmasked, and single group. In general, random assignment helps balance measured and unmeasured participant characteristics across groups on average; without it, groups may differ for reasons other than treatment. Here, the two dose cohorts are not identified as randomized comparison arms, and no untreated or placebo group is described. The cohort schedule also differs: Cohort A began at 3 g twice daily and could continue at 6 g twice daily if safe, while Cohort B received 6 g twice daily for the duration of the study. Thus a simple contrast between cohorts would not isolate a dose effect.

Over-dispersion is a general concern for outcomes whose observed variability exceeds what a statistical model assumes. If the model understates variability, estimated uncertainty can be too small and tests can appear more decisive than warranted. The primary endpoint is continuous, and the registry identifies standard deviation as its dispersion measure; however, the record does not report an analysis model or whether over-dispersion was assessed. It would be inappropriate to infer a particular model or diagnostic procedure.

The registry lists no analyses. The statistical plan, any prespecified hypotheses, handling of repeated measurements, and adjustment method are not reported in the registry record. The primary endpoint title specifies a mean and baseline adjustment, but that information alone does not establish whether the analysis used a model, how missing measurements were handled, or how uncertainty was calculated.

The record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations: they estimate a sample size under stated assumptions, not the power observed in the completed study. They do not establish the trial’s original design rationale. The registry does not report a sample-size justification for the trial, and the numerical planning results are not reported in the registry record.

For general interpretation, a planned sample size can be sensitive to assumptions about effect size, variability, allocation, and analysis. A calculation based on the observed effect is especially dependent on that effect estimate and should not be treated as independent confirmation of it. The registry’s stated planning assumptions do not supply a numerical endpoint estimate, and no sample-size illustration should be read as evidence that the study had a particular observed power.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("ManNAc: Cohort A", "ManNAc: Cohort B")
n   <- c(6, 6)
m   <- c(7461, 9432)
sp  <- c(1776, 2710)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  ManNAc: Cohort A  6  7461.000  1776.000  5597.202  9324.798
CARM  ManNAc: Cohort B  6  9432.000  2710.000  6588.029  12275.971

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and no analyses. It does not report which outcomes were designated as secondary or exploratory, whether multiple hypotheses were tested, or whether any adjustment for multiple comparisons was planned or used. The multiplicity plan is therefore not reported in the registry record. In general, when many hypotheses are tested, the chance of at least one apparently unusual result can increase; adjustment methods can address that issue, but no particular method can be attributed to this study from the record.

Missing-data methods are also not reported in the registry record. The endpoint description does not say how missing samples, incomplete concentration profiles, or values that could not be quantified were handled. The record does not report the amount or pattern of missing primary endpoint data, or whether all subjects who received ManNAc contributed to the analysis.

The primary endpoint population is described as all subjects who received ManNAc. The registry does not provide a more detailed analysis-population definition, such as rules for including or excluding subjects, nor does it report an intention-to-treat or per-protocol analysis. No analysis details are listed. These gaps matter because population definitions and missing-data methods can affect the estimate and its uncertainty, especially in a small, nonrandomized study. The registry record does not provide enough information to assess those effects.

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 registry lists serious adverse events for three exposure categories. In ManNAc 3 g - 7 Days, 0 of 6 subjects at risk were listed as having a serious adverse event. In ManNAc 6 g - 7 Days, 0 of 6 were listed. In ManNAc 6 g - Day 8 to 30 Months, 0 of 12 were listed. The registry also lists 0 deaths in each category.

Other adverse events are listed for 5 of 6 subjects in the ManNAc 3 g - 7 Days category, 6 of 6 in the ManNAc 6 g - 7 Days category, and 12 of 12 in the ManNAc 6 g - Day 8 to 30 Months category. These counts describe what the registry reports for each exposure category; they do not by themselves establish that ManNAc caused an event. The record does not provide the event terms or additional clinical context, and its list of top serious terms is empty.

The categories have different dose and duration descriptions and are not stated to be independent groups. The registry does not explain whether subjects appear in more than one category. Therefore, the counts should be read category by category, not added together or treated as a randomized safety comparison. Zero listed serious events does not establish that serious events cannot occur.

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

The record establishes what the study set out to measure and how its dose cohorts were described. Its primary endpoint was a baseline-adjusted mean plasma ManNAc AUC at Day 7, a measure of pharmacokinetic exposure. The registry does not report the numerical endpoint result, its standard deviation, or a confidence interval. As a result, the magnitude and precision of the endpoint estimate cannot be evaluated from the record.

The study was nonrandomized, open-label, and listed as a single-group model. It does not include a stated placebo or untreated comparison. Cohort A and Cohort B had different dosing schedules, and the registry does not describe randomized assignment. The cohort descriptions therefore do not support a causal comparison of dose levels.

The safety listings report no serious adverse events or deaths in the displayed exposure categories and report other adverse events in each category. These are descriptive counts, not proof of absence of risk and not estimates of treatment-caused harm. The registry does not report event-level details or explain whether the exposure categories overlap.

The clinical rationale in the registry summary concerns ManNAc as a precursor in cellular sialic acid production, in the context of GNE myopathy. That rationale provides context for why ManNAc was studied, but it does not convert a plasma exposure endpoint into evidence about muscle function or patient experience. The record’s described primary endpoint does not directly measure those outcomes.

Accordingly, the registry information can describe the study design, dosing schedules, endpoint definition, and listed safety counts. It cannot establish a treatment effect, comparative effectiveness, or the clinical importance of a pharmacokinetic change. Numerical results for the primary endpoint and statistical analyses are not reported in the registry record, so conclusions beyond those descriptive details are not supported by the posted information.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a trial’s design, its endpoint, and its results. The registry describes a nonrandomized Phase 2 study with two dose cohorts, but that design does not create a randomized dose comparison. Cohort differences may reflect more than the assigned dose, and no control group is described.

The primary endpoint is a pharmacokinetic measure: baseline-adjusted plasma ManNAc AUC at Day 7. It can characterize exposure, but it is not itself a measure of muscle strength, mobility, or disease progression. Keeping the endpoint’s measurement target clear prevents a pharmacokinetic result from being interpreted as a clinical outcome.

The record also illustrates why an endpoint definition is not enough to evaluate evidence. The registry identifies the summary measure and its dispersion measure, yet does not report the numerical mean, standard deviation, confidence interval, or analysis. Without those details, readers cannot assess the estimate’s magnitude or precision. A completed-study status does not fill in those missing statistical results.

Finally, the safety listings show why denominators, exposure periods, and group definitions matter. The registry gives counts for categories with different dose and duration descriptions, but does not explain whether the categories overlap. Treating these listings as independent comparisons or combining them would go beyond what the record supports. Careful interpretation separates descriptive counts from causal evidence.

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 registry record leaves important details of the study and its analysis unreported. It does not explain how subjects entered the two dose cohorts, whether cohort assignment depended on clinical characteristics, or whether participants’ treatment histories differed in other ways. Since allocation was nonrandomized, the dose cohorts cannot be assumed to be balanced or directly comparable.

The primary endpoint is defined, but its numerical result is not reported. The registry also does not report the standard deviation, confidence interval, or statistical test for that endpoint. Details of the sampling schedule, AUC calculation, baseline adjustment, and handling of measurements that were not quantifiable are not reported in the registry record.

The record lists 7 outcome measures but no analyses. It does not describe the statistical plan, missing-data approach, analysis populations beyond the primary endpoint’s stated population, or any multiplicity procedure. These omissions prevent assessment of how the reported outcomes were analyzed and how uncertainty was handled.

The safety categories differ in dose and exposure period, and the registry does not clarify whether the categories represent separate participants or repeated exposure periods for some subjects. Event details are not reported in the safety listing, and an empty list of top serious terms does not provide additional clinical context. These limitations mean the counts are descriptive and should not be treated as a comparative or causal safety analysis.

Finally, the registry describes a planning illustration based on the observed effect but does not report its numerical results or the trial’s own sample-size justification. The illustration cannot establish the study’s original design assumptions or observed power. These limitations are specific to what this registry record reports; additional details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open Label Phase 2 Study of ManNAc in Subjects With GNE Myopathy — NCT02346461.
• Registry record last updated 2019-04-16; status last verified 2019-03.
• Results first posted 2019-04-16.
• 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

NCT02346461 is listed as a completed, open-label Phase 2 study of ManNAc in subjects with GNE myopathy. The registry describes a nonrandomized, single-group model, enrollment of 12, and two dose cohorts. Cohort A began at 3 g twice daily and could continue at 6 g twice daily if safe; Cohort B received 6 g twice daily for the duration of the study.

The primary endpoint was baseline-adjusted mean plasma ManNAc AUC at Day 7, measured from dosing to the last quantifiable concentration. Its numerical result and dispersion are not reported in the registry record. The safety listings report no serious adverse events or deaths in the stated exposure categories, alongside other adverse events. The record lists 7 outcome measures and no analyses, so the endpoint’s magnitude, precision, and analysis cannot be assessed from the registry information.