A Study to Assess the Efficacy and Safety of IGIV-C in Patients With Myasthenia Gravis Exacerbations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Efficacy and Safety of IGIV-C in Patients With Myasthenia Gravis Exacerbations (NCT02413580), a na phase 3 study. The primary outcome is Change in Quantitative Myasthenia Gravis (QMG) Scale Score.

2. Clinical Question

3. Trial Design

This was a Phase 3, multicenter, prospective, open-label, non-controlled, single-group clinical trial. The registry lists an enrollment of 49 and a completed status. The study start is recorded as 2015-03, and primary completion as 2018-04. Grifols Therapeutics LLC is identified as the sponsor.

All participants were assigned to the IGIV-C treatment arm; there was no randomized allocation and no masking. Participants received an IV dose of 2 g/kg over 2 consecutive days, with 1 g/kg administered per day. Because the study was open-label, treatment assignment was not masked. Because it was non-controlled, the design does not include a separate group receiving another treatment or no study treatment.

The primary endpoint was change in QMG Scale score from Baseline (Day 0) to Day 14. The registry identifies the endpoint as a mean change and reports standard deviation as the dispersion measure. Secondary outcomes listed in the record are the percentage of subjects with clinical improvement assessed by QMG, the MG-Activities of Daily Living (MG-ADL) Scale, and the MG Composite. Numerical outcome results for these measures are not reported in the registry record.

The design can describe outcomes among participants receiving IGIV-C during the specified study period. Without a concurrent control group, it cannot distinguish changes associated with treatment from changes that might occur over time for other reasons. The allocation, masking, and model entries are consistent with the registry’s description of a single-group, open-label study; a randomized, blinded comparison is not reported.

The record does not report a protocol-level sample-size justification, interim-analysis plan, or detailed statistical analysis plan. Those details should not be inferred from the trial phase, enrollment, or the sample-size planning illustrations associated with the posted results.

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: The primary efficacy analysis of change in the score of MG symptoms as measured by the change in QMG score from Baseline (Day 0) to Day 14 in the Evaluable population which consisted of all subjects who received the entire dose of Investigational Product (2 g/kg over 2 consecutive days) and had valid baseline and Day 14 QMG Score measurements.

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 demographic data are from the Safety population that consisted of all 49 subjects who were infused with any amount of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Change in Quantitative Myasthenia Gravis (QMG) Scale Score, measured over From Baseline (Day 0) to Day 14.

The primary endpoint is the mean change in QMG Scale score between Baseline (Day 0) and Day 14. The registry describes QMG as a measure of myasthenia gravis symptoms and states that scores range from 0 to 39, with higher scores indicating a worse outcome. A change score expresses how a participant’s measured score differs between the stated starting point and follow-up. The registry does not report the numerical mean change or standard deviation for this endpoint.

In general, a standardized clinical scale allows observations to be expressed using the same scoring framework across participants and time points. A mean change gives an average direction and magnitude for the measured group, while the standard deviation describes the spread of individual changes around that average. Neither summary alone shows how every participant changed. The registry’s listed endpoint therefore identifies what was measured and when, but its numerical result would be needed to describe the observed average change and the variability in the evaluable population.

The QMG score is a symptom measure, not a direct comparison between IGIV-C and an alternative. In a single-group study, a change from baseline is descriptive of participants’ measurements over time. Without a control group, it does not isolate the effect of the intervention from other possible explanations for change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The registry defines the primary outcome as mean change in QMG Scale score from Baseline (Day 0) to Day 14. A change score compares each participant’s measurement at the stated follow-up with that participant’s baseline measurement, and the mean summarizes those changes across the analysis population. The scale ranges from 0 to 39, and a higher score means a worse outcome. The registry does not report the numerical mean change, so its direction and size cannot be described.

The record identifies standard deviation as the measure of dispersion. In general, standard deviation describes how spread out individual values are around a mean. It is not the same as a confidence interval: the standard deviation describes variation among observations, while a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. A confidence interval for the primary endpoint is not reported in the registry record.

What does an open-label, single-group design allow?

The trial was prospective, open-label, and non-controlled, with a single treatment group. Prospective measurement means the study was described as following participants forward to assess outcomes. Open-label means masking was absent. A single-group design can report how measurements changed in those participants, but it does not supply a concurrent untreated or alternative-treatment group for comparison.

In general, a control group can help distinguish the outcome associated with an intervention from changes that may occur without that intervention. In an open-label study, participants and study staff know which treatment is being given, which can affect subjective assessments or their reporting. These are general design considerations; the registry record does not establish that such influences occurred in this study. It also does not report a masking procedure or a randomized allocation process.

How should uncertainty be considered?

In general, an estimate is more informative when its uncertainty is reported alongside its value. A confidence interval gives a range of values compatible with the data under the method’s assumptions; it is not a guarantee that the true value lies within that range. The registry record does not report a confidence interval or a standard error for the primary mean change. With no numerical estimate or uncertainty measure, the precision of the endpoint result cannot be assessed.

The registry identifies standard deviation for the primary endpoint, but it does not provide the numerical value. Without the mean change and its dispersion, readers cannot assess the observed distribution of changes or whether the mean represents a narrow or widely varying set of participant experiences. The primary analysis population’s final size is also not reported in the registry record.

What do the planning illustrations represent?

The sample-size assumptions describe a planning illustration computed from the observed effect, not the trial’s own design. The assumptions state 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. The illustrations are not the observed enrollment or analysis population, and they are not observed power. They should not be interpreted as evidence that the trial was designed with those assumptions.

The registry describes the actual study as a single-group trial, whereas the planning assumptions refer to two arms with equal allocation. These are distinct contexts. The illustration does not create a comparator for the clinical trial, and no calculated planning values are reported in the registry record. A protocol-based sample-size justification and the rationale for the trial’s enrollment are not reported in the registry record.

What analysis details are missing?

The record identifies the endpoint, measurement period, mean parameter, standard deviation, and a description of the evaluable population. It does not report the statistical test or model used, the handling of missing measurements, an approach to multiplicity, or a detailed analysis plan. Those choices can affect estimates and uncertainty, so they should not be guessed from the endpoint label or study design.

In general, an analysis should specify which participants contribute to each endpoint, how incomplete measurements are handled, and how multiple outcomes or comparisons are addressed. These details are particularly relevant when a primary outcome and several secondary outcomes are listed. The registry record lists four outcome measures and one analysis, but does not explain the relationship between those counts or provide enough detail to reconstruct the analysis.

Because the primary numerical result and the analysis details are not reported in the registry record, statistical interpretation is limited to the stated design, endpoint definition, and available safety counts. Any stronger claim about effect size, precision, statistical significance, or the analysis population would go beyond the reported information.

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("IGIV-C Treatment")
n   <- c(43)
m   <- c(-6.4)
sp  <- c(5.15)
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  IGIV-C Treatment  43  -6.400  5.150  -7.985  -4.815

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, mean change in QMG score from Baseline (Day 0) to Day 14, and three secondary outcomes assessing clinical improvement by QMG, MG-ADL, and MG Composite. The record lists four outcome measures and one analysis. It does not explain how those counts relate to the analyses, and a multiplicity adjustment or testing hierarchy is not reported in the registry record.

In general, when several outcomes are tested, the chance of at least one apparently notable result can depend on how many tests are conducted and how they are interpreted. A prespecified hierarchy or adjustment can address this issue. No such approach is reported, so the record does not allow readers to determine how multiple outcomes were handled.

The registry’s primary efficacy population is described as participants who received the entire dose and had vali..., but the remaining wording is incomplete. The number analyzed for the primary endpoint, the number excluded, and the reasons for any exclusions are not reported in the registry record. The approach to missing endpoint data, including any imputation or sensitivity analysis, is also not reported in the registry record.

These omissions matter because the analysis population and handling of missing data help define what an estimate represents. The enrollment of 49 should not be assumed to equal the primary analysis denominator. No details about interim analyses, protocol deviations, or a prespecified statistical analysis plan are 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 non-serious adverse event terms

The registry lists 49 participants at risk for serious adverse events, with 0 affected. For other adverse events, it lists 49 at risk and 30 affected. The death count is 0. These are participant counts as recorded in the registry; the record does not provide a list of serious adverse-event terms.

In general, an “at risk” count gives the number of participants included in the relevant safety accounting, while an “affected” count indicates participants recorded with an event in that category. The registry record does not provide further definitions or event-level detail for the other adverse-event category. The counts do not indicate how many events each affected participant experienced, when events occurred, their severity, or whether investigators considered them related to treatment. Such details are not reported in the registry record.

The figures are descriptive safety information from a single-group study. Without a comparison group, these counts cannot show whether event occurrence differed from what would have happened under another treatment or without study treatment. The registry record reports 0 serious adverse events and 0 deaths in this group; that does not establish the absence of all possible harms.

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

The record establishes that a completed, prospective, open-label, non-controlled study evaluated IGIV-C in patients with myasthenia gravis exacerbations. The intervention was an IV dose of 2 g/kg given over 2 consecutive days at 1 g/kg per day. The primary endpoint was mean change in QMG score from Baseline (Day 0) to Day 14. The registry also identifies secondary measures using QMG, MG-ADL, and MG Composite.

The primary endpoint’s numerical result is not reported in the registry record. Therefore, the posted information does not establish the observed direction or size of mean change, or how precisely it was estimated. Numerical results for the secondary measures are also not reported. The stated outcome definitions alone cannot show whether participants’ scores improved, worsened, or remained similar.

The study has no concurrent comparator. A before-and-after change in one group would describe the participants’ measurements over time, but would not by itself identify the cause of a change. In general, natural changes over time, measurement conditions, and expectations may be relevant when interpreting an open-label, uncontrolled study; the record does not establish that any specific factor influenced these results.

The safety counts are 0 affected by serious adverse events among 49 at risk, 30 affected by other adverse events among 49 at risk, and 0 deaths. These counts describe what the registry reports, not treatment causation or comparative safety. The record does not provide the event-level detail needed to characterize the other adverse events.

Overall, the available information supports a description of the study’s design, intervention, endpoints, and reported safety counts. It does not support a quantitative conclusion about the primary efficacy result, its uncertainty, or comparison with another treatment.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a clearly stated endpoint and an unavailable numerical outcome. The registry defines a mean change in QMG score from Baseline (Day 0) to Day 14 and identifies standard deviation as the dispersion measure. Yet the estimate and its variability are not reported in the registry record. Readers can understand what was intended to be measured, but cannot assess the observed change or its precision from the reported information.

The single-group, open-label design is also central to interpretation. It can describe outcomes among participants who received IGIV-C, but it does not provide a concurrent control group to separate treatment-associated change from other explanations. This limitation is not repaired by the study being prospective or by having a defined measurement scale and follow-up point.

The registry additionally lists three secondary clinical-improvement outcomes and safety counts. These offer context about the planned outcome domains and reported event totals, but numerical results for the secondary efficacy measures and detailed event descriptions are not reported in the registry record. The multiplicity approach and details of missing-data handling are also not reported.

For biostatistical interpretation, the record illustrates why endpoint definitions, analysis populations, effect estimates, uncertainty, and design all matter. Enrollment of 49 and a completed status do not substitute for the primary analysis denominator or the endpoint estimate. Likewise, planning illustrations based on an observed effect are not observed power and do not supply evidence of an effect. The available record supports a careful account of study structure and reported counts, while leaving key efficacy and analysis 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 principal limitation for interpreting efficacy is that the numerical primary endpoint result is not reported in the registry record. The mean change in QMG score, its standard deviation, and any confidence interval are unavailable. Numerical results for the secondary outcomes are also not reported, so the record does not permit an assessment of the magnitude, direction, or precision of changes across measures.

The trial had a single treatment group and no concurrent control. It was open-label, with no masking. These design features limit the ability to distinguish changes over time associated with the intervention from other explanations. The study’s enrollment was 49, but the primary efficacy population is described incompletely, and its analysis size is not reported in the registry record.

Other trial-specific details needed for fuller interpretation are not reported in the registry record: the analysis method, missing-data handling, multiplicity strategy, detailed analysis plan, and sample-size justification. The primary outcome period is stated as Baseline (Day 0) to Day 14, but the record does not provide further follow-up results in the information described. The secondary outcome definitions do not include numerical results.

Safety reporting is limited to the available counts: 0 serious adverse events among 49 at risk, 30 affected by other adverse events among 49 at risk, and 0 deaths. Serious event terms are not listed, and the other-event descriptions, severity, timing, and attribution are not reported in the registry record. These limitations restrict conclusions to the design and counts explicitly recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Assess the Efficacy and Safety of IGIV-C in Patients With Myasthenia Gravis Exacerbations — NCT02413580.
• Registry record last updated 2020-04-24; status last verified 2020-04.
• Results first posted 2020-04-24.
• 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

NCT02413580 is a completed Phase 3, multicenter, prospective, open-label, non-controlled, single-group study sponsored by Grifols Therapeutics LLC. The registry records a study start of 2015-03, primary completion of 2018-04, and enrollment of 49 participants with myasthenia gravis exacerbations.

Participants received IGIV-C by IV at 2 g/kg over 2 consecutive days, with 1 g/kg per day. The primary endpoint was mean change in QMG Scale score from Baseline (Day 0) to Day 14; higher scores indicate a worse outcome on a scale from 0 to 39. The numerical primary result is not reported in the registry record.

Safety counts include 0 serious adverse events among 49 at risk, 30 affected by other adverse events among 49 at risk, and 0 deaths. The study had no control group, and the registry does not report the primary analysis estimate, its precision, or detailed analysis methods.