Study to Assess Safety and Efficacy of Engensis in Painful Diabetic Peripheral Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Safety and Efficacy of Engensis in Painful Diabetic Peripheral Neuropathy (NCT04469270), a randomized phase 3 study. The primary outcome is Efficacy of Engensis Compared to Placebo Painful Diabetic Peripheral Neuropathy in Feet and Lower Legs Comparing Average Daily Pain Score From Day 0 Visit to Day 180 Visit on Brief Pain Inventory for Participants With Diabetic Peripheral Neuropathy.

2. Clinical Question

The primary endpoint is a continuous pain score, not a count of participants who crossed a response threshold. Its scale runs from 0 to 10, with higher scores indicating worse pain. The comparison therefore concerns the average change in score in each randomized group and the difference between those changes as posted.

The clinical question is framed as a comparison, not as a claim about what any participant should expect. The reported group averages describe the enrolled trial population; they do not by themselves establish how results would apply to people with different characteristics, treatment schedules, or clinical settings. The registry record does not report additional eligibility details in the registry record considered for this analysis.

3. Trial Design

The registry describes a completed, randomized, parallel-group, placebo-controlled Phase 3 study. Its official title calls it adaptive, double-blind, and multicenter, and the masking field reports quadruple masking. Those labels describe the recorded design, but the detailed procedures for allocation, masking, or adaptation are not reported in the registry record.

The total enrollment is 162. The primary endpoint results include 79 participants in the Engensis group and 81 in the placebo group. The record says 81 participants were randomized to Engensis; 2 were never dosed and were withdrawn on Day 0. The reported Engensis endpoint sample is therefore smaller than its randomized group. The record labels the primary summary as intent-to-treat, but does not explain further how the analysis population was defined or how the two withdrawals were handled for endpoint analysis.

Engensis was given by intramuscular injections into both gastrocnemius muscles on Days 0, 14, 90, and 104. The placebo arm used the same described injection locations and schedule. The primary outcome was measured at Day 180. The registry lists the study start as 2020-11-20 and primary completion as 2023-03-24, with status completed.

The record also lists secondary outcomes involving worst pain, a threshold reduction in average daily pain, adverse events and laboratory findings, and possible cellular and humoral responses. The registry record does not report the original sample-size justification, the operational details of any adaptive design, or the statistical analysis plan. Those design details should not be inferred from the title or from the posted outcome summaries.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Summary of the Actual Value of the Change from Baseline to Day 180. 81 subjects were randomized to Engensis. Two Engensis subjects were never dosed and were withdrawn from the study on Day 0, therefore do not fall into the safety population.

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: ITT Population

6. Primary Endpoint

The registry lists the primary outcome as Efficacy of Engensis Compared to Placebo Painful Diabetic Peripheral Neuropathy in Feet and Lower Legs Comparing Average Daily Pain Score From Day 0 Visit to Day 180 Visit on Brief Pain Inventory for Participants With Diabetic Peripheral Neuropathy, measured over 180 days.

The primary endpoint is the change from baseline to Day 180 in average daily pain score, measured using the Brief Pain Inventory for Participants with Diabetic Peripheral Neuropathy. The record defines the scale as ranging from 0 to 10, with higher scores representing worse pain. Change is expressed as the Day 180 value relative to Day 0, so a negative change represents a lower score at follow-up than at baseline.

A continuous score retains information about the degree of change across the scale. This differs from classifying participants only as responders or nonresponders at a chosen threshold. Comparing group means gives a summary of the average change, while the standard deviations describe how widely individual scores vary around those group averages. Neither summary describes every participant’s experience.

The registry reports a mean change of -2.03 in the Engensis group and -2.69 in the placebo group. The primary comparison is a mean difference of 0.66, with a confidence interval from 0.019 to 1.301. In the direction used for this comparison, the positive difference reflects the less negative average change in the Engensis group than in the placebo group. These are posted group summaries; they do not show the full distribution of individual changes or explain how missing Day 180 measurements were handled.

The endpoint is useful for describing average pain-score change over the stated follow-up, but its interpretation depends on the measurement scale, the population analyzed, and the analysis procedures. Further details about those procedures are not reported in the registry record.

7. Results Posted in the Registry

• Engensis: mean -2.03 versus -2.69 on control; difference 0.66 (95% CI 0.02 to 1.30), standardized effect d = 0.32; z-test p = 0.044.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Efficacy of Engensis on Worst Pain in Painful Diabetic Peripheral Neuropathy in Feet and Legs by Comparing Change From Baseline (Day 0) in Worst Pain Score From Brief Pain Inventory for Diabetic Peripheral Neuropathy to Day 180 Compared to Placebo

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Engensis: mean -2.10 versus -3.06 on control; difference 0.96 (95% CI 0.19 to 1.73), standardized effect d = 0.39; z-test p = 0.014.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Engensis than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Efficacy of Engensis Reducing Painful Diabetic Peripheral Neuropathy in Feet and Legs by Determining a ≥ 50% Reduction in the Average Daily Pain Score From Baseline to Day 180 Using the Brief Pain Inventory With Participants Diabetic Peripheral Neuropathy

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Engensis: 30.4% (24/79) versus 40.7% (33/81) on control; risk difference -10.4 percentage points (95% CI -25.1 to 4.4), risk ratio 0.75 (0.49–1.14); unadjusted two-proportion z-test p = 0.171.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Engensis and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results follow a pattern broadly similar to the primary continuous outcome: the mean change in worst pain was more negative in the placebo group than in the Engensis group. The threshold-based responder outcome also had fewer participants meeting the stated reduction threshold in the Engensis group than in the placebo group. These directions are consistent with the primary group-average contrast, but each measure captures a different aspect of pain change.

The secondary results do not all have the same uncertainty. The interval for the worst-pain mean difference is positive, while the interval for the risk difference in the responder outcome includes zero. This contrast illustrates why the continuous mean and threshold count should be interpreted separately. A group-average difference does not imply the same pattern for the proportion meeting a response definition, and dichotomizing an outcome can discard information about the size of each participant’s change.

These outcomes relate to the primary result by examining other summaries of pain at the same stated follow-up, not by serving as independent replications. The secondary list also includes safety, laboratory, and immune-response questions. Results for all those listed outcomes are not present in the registry record, and full secondary analyses are not reported in the registry record.

The secondary p-values are unadjusted, and the registry record does not report a multiplicity strategy or a hierarchy specifying which secondary tests should be treated as confirmatory. When several outcomes are assessed, a small unadjusted p-value can be less persuasive than the same result from a single prespecified test because repeated testing increases the opportunity for chance findings. For that reason, the secondary results carry less weight than a fully specified, multiplicity-controlled confirmatory analysis would carry. They are useful for describing the pattern of posted findings, but should not be treated as definitive evidence in isolation.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Efficacy of Engensis on Worst Pain in Painful Diabetic Peripheral Neuropathy in Feet and Legs by Comparing Change From Baseline (Day 0) in Worst Pain Score From Brief Pain Inventory for Diabetic Peripheral Neuropathy to Day 180 Compared to Placebo
• Efficacy of Engensis Reducing Painful Diabetic Peripheral Neuropathy in Feet and Legs by Determining a ≥ 50% Reduction in the Average Daily Pain Score From Baseline to Day 180 Using the Brief Pain Inventory With Participants Diabetic Peripheral Neuropathy
• Safety of Engensis in Painful Diabetic Peripheral Neuropathy in Feet and Legs Comparing Incidence of Adverse and Serious Adverse Events, Incidence of Injection Site Reactions, and Incidence of Clinically Significant Laboratory Values to Placebo
• To Evaluate the Possibility of Cellular Responses to Engensis
• To Evaluate the Possibility of Humoral Responses to Engensis - Anti-Hepatic Growth Factor

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant’s change is represented by a score, and the registry summarizes those scores with a mean and standard deviation. A mean gives the arithmetic average within a group. A standard deviation describes the spread of individual values around that average. These answer different questions: the mean describes the group’s average change, while the standard deviation describes variability among participants.

What does the mean difference represent?

The posted comparison is a mean difference of 0.66 for Engensis relative to placebo. The arm means are -2.03 and -2.69, respectively. The positive difference follows from comparing the less negative Engensis change with the more negative placebo change. Since the endpoint is a change score and higher pain scores are worse, signs need to be interpreted in that stated direction. The difference is not a percentage change and is not the difference between the groups’ Day 180 scores alone.

The registry also reports a pooled standard deviation of 2.069 and a standardized effect size of 0.319. Standardizing expresses the group contrast in units of the pooled variability, which can help compare effects measured on different scales. It does not change the clinical scale or turn the estimate into a probability of benefit. These summaries do not establish whether a difference is important to participants; a threshold for clinical importance is not reported in the registry record.

What does the unadjusted p-value say?

The primary unadjusted p-value is 0.044. In general, a p-value describes how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that the null hypothesis is true, nor is it the probability that the result occurred by chance. The registry record does not report the full analysis model, the exact test procedure, or any adjustment applied to this comparison. The posted p-value should consequently be read as unadjusted.

Unadjusted means that the reported value has not been adjusted for a collection of comparisons. When multiple endpoints or analyses are considered, the chance of seeing at least one apparently unusual result can be higher than for a single prespecified comparison. General statistical practice may address this with prespecified testing sequences or multiplicity adjustments, but the registry record does not report such procedures for these results.

How should the confidence interval be read?

A confidence interval describes uncertainty in an estimated quantity under a statistical procedure. The primary mean-difference interval runs from 0.019 to 1.301. Under the assumptions of that procedure, the interval identifies values that are reasonably compatible with the observed data and method. It is not a range containing a known proportion of individual participant outcomes, and it does not mean that there is a particular probability that the true value lies inside this specific interval.

The interval’s lower endpoint is near zero, while the upper endpoint is farther from zero. Thus, the posted estimate is more precise about the direction than about the size of the difference: values across a range of positive magnitudes remain compatible with the result. This does not resolve whether any value in that range is clinically important.

Why do spread and assumptions matter?

Participant outcomes vary. Greater spread generally makes it harder to estimate a group difference precisely when sample sizes are otherwise comparable. General statistical methods for continuous outcomes often rely on assumptions about the sampling distribution or use procedures designed to be robust to departures from assumptions. The record gives group standard deviations and a pooled standard deviation, but the precise model and diagnostic checks are not reported in the registry record. The pooled value should not be taken as proof that group variances or outcome distributions were identical.

The outcome description identifies the primary summary as intent-to-treat and reports 79 Engensis participants. It also says 81 were randomized to Engensis, with 2 never dosed and withdrawn on Day 0. The endpoint sample count in placebo is 81. The registry record does not give a full participant flow for endpoint availability, explain treatment of missing scores, or specify imputation or sensitivity analyses. Such details matter because an analysis of observed scores can differ from an analysis that makes assumptions about participants without a recorded Day 180 value.

The registry says the study was randomized and parallel-group, and its official title describes double-blind conduct; the masking field says quadruple. Random allocation can help make groups comparable on average, while masking can limit some forms of bias. These are general design considerations. The registry record does not provide details sufficient to assess allocation concealment, which parties were masked, or whether masking remained intact.

Secondary measures include another continuous pain score and a binary responder outcome. A binary outcome records whether a participant met a threshold, rather than the amount of change for each participant. It can communicate a threshold-based result, but results depend on the chosen cutoff and may discard information about changes that fall short of it. The mean-difference and risk-difference estimates therefore address distinct summaries and should not be treated as interchangeable.

11. Confidence Intervals and Precision

The primary mean-difference estimate is 0.66, with a confidence interval from 0.019 to 1.301. The interval expresses uncertainty around the group contrast, rather than variation among individual participants. Its endpoints are both positive, but the lower endpoint is close to zero. The interval therefore allows for a small positive difference as well as appreciably larger positive differences, under the method used to calculate it.

Precision is also shaped by the observed variability and the number of participants contributing to the comparison. The primary arm summaries report standard deviations of 2.02 and 2.115, with 79 and 81 participants. Those figures give context for the uncertainty, but they do not reveal whether observations were complete for all randomized participants or how missing values were treated. The record states that 2 Engensis participants were never dosed and withdrawn on Day 0, while the primary summary is labeled intent-to-treat. Further analysis-population details are not reported in the registry record.

A confidence interval is not a prediction interval for individual responses, and it is not a statement that every value within its limits is equally plausible. It also does not determine clinical importance. The registry record does not report a threshold for a meaningful difference on this scale, so the interval cannot be classified by such a threshold using the posted information alone.

Precision should be considered alongside the unadjusted p-value of 0.044 and the presence of other outcomes. The interval and p-value summarize the same primary contrast in related ways; they are not independent evidence. No multiplicity adjustment is reported in the registry record, so the interval should not be interpreted as if it had been adjusted to account for all outcomes or analyses.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size table gives planning illustrations in participants per arm for the continuous and binary outcomes. These are not total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row uses a stated fraction of the observed effect as the effect to detect. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm under those assumptions for a design with an 80% chance of detecting the specified effect if that effect is the true one and the model assumptions apply. The 90% power column makes the same planning calculation for a 90% chance. These are design probabilities under a hypothetical planning model, not probabilities that the trial result is correct.

Rows for a smaller fraction of the observed effect require more participants per arm. This reflects a general feature of study planning: smaller group differences are harder to distinguish from sampling variation, so a larger sample is usually needed to attain a given planned power under otherwise fixed assumptions. The table’s values change with both the effect used and the selected power target.

The curve should be read as a visual depiction of the planning relationship between the effect size used and the sample size indicated by the stated assumptions. The figures are planning illustrations based on the observed effect, not observed power. They do not show the trial’s actual enrollment target rationale or prove that the completed study had a particular probability of detecting an effect.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.660; pooled standard deviation σ = 2.069.
2. n = 2 × (1.96 + 0.842)² × 2.069² / 0.660² = 154.2, rounded up to 155 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.66                      # observed difference in means
sigma <- 2.0686465947999                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4469270)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 155 (80% power), 207 (90% power)
 75% of observed effect: n per arm = 275 (80% power), 368 (90% power)
 50% of observed effect: n per arm = 617 (80% power), 826 (90% power)
power.t.test: 155.2 
Simulated power at n = 155 per arm: 0.791 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, including continuous pain measures, a threshold-based response, safety outcomes, and immune-response questions. The presence of multiple outcomes raises a multiplicity question: if many hypotheses are tested, the chance of at least one low p-value under null conditions can increase. This is a general statistical concern, not a claim that the study used a particular testing strategy.

The posted p-values for the primary and the reported secondary comparisons are unadjusted. A multiplicity adjustment, a prespecified testing hierarchy, or another method for controlling the interpretation of multiple tests is not reported in the registry record. The secondary outcome entries contain no reported analyses. Consequently, the posted results cannot establish how the study team planned to prioritize secondary outcomes or whether other analyses were conducted.

Missing-data handling is also not reported in the registry record. The primary description labels its summary intent-to-treat and says that 81 participants were randomized to Engensis, of whom 2 were never dosed and withdrawn on Day 0. It reports an Engensis primary endpoint sample of 79 and a placebo sample of 81. That information does not explain whether other Day 180 measurements were missing, how the analysis population was operationalized, or whether any imputation or sensitivity analyses were used. Those details are important because conclusions from available measurements may depend on who contributed outcome data and on assumptions about absent measurements.

The record does not report the analysis model, covariate adjustment, prespecified contrasts, interim analyses, or a statistical analysis plan. The study title uses the term adaptive, but the specific adaptive procedures are not reported in the registry record. These omissions limit assessment of prespecification, protection against selective analysis, and the relationship between the posted summaries and the trial’s intended confirmatory analysis.

15. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (1.3%), cardiac failure acute (1.3%), pericardial effusion (1.3%), tachycardia (1.3%), enteritis (1.3%).

The registry reports serious adverse event counts for 79 Engensis participants and 81 placebo participants. Serious adverse events are listed for 7 in the Engensis group and 4 in the placebo group. The record also reports 38 participants with other adverse events in the Engensis group and 41 in the placebo group. Deaths are listed as 1 and 0, respectively. These are descriptive counts; they do not establish that treatment caused an event or that an event was unrelated to treatment.

The record lists serious-event terms including acute myocardial infarction, cardiac failure acute, pericardial effusion, tachycardia, enteritis, and constipation, each reported as 1.3%. These terms and figures should be read as registry entries, not as a complete account of clinical circumstances, timing, severity, or causal assessment. The registry record does not provide those details in the registry record.

Comparing adverse-event counts requires attention to the number at risk and to the way events or affected participants were counted. The posted group sizes differ, and the posted counts do not give event-level timing or exposure duration. The counts therefore describe what was recorded in each group, but are not by themselves a full comparative safety analysis.

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

The posted primary results describe average changes in pain scores over the trial’s stated follow-up. Both groups had negative mean changes, with a more negative group mean in placebo than in Engensis. The estimated mean difference is 0.66, and its confidence interval ranges from 0.019 to 1.301. This is the statistical comparison reported for the primary outcome; it does not establish a treatment effect for every participant or answer how results would generalize beyond the trial population.

The result does not show that every participant’s pain changed in the same way. The standard deviations indicate variability around group means, and group summaries cannot identify individual trajectories. The registry record also does not provide the full distribution of scores, participant-level data, or enough information about missing outcome measurements to assess how those issues may affect the estimate.

The unadjusted p-value of 0.044 should be considered with the confidence interval, the multiple outcomes, and the absence of reported multiplicity procedures. It is not a measure of the probability that the result is true or of the size or importance of a difference. The registry record does not report a threshold for clinical importance, so statistical evidence and clinical importance cannot be equated using these registry entries.

Nor do the posted secondary results replace the primary comparison. They address worst pain and a response threshold, among other listed outcomes, and their uncertainty differs. The record does not report all analyses for the broader secondary outcome list or the statistical plan governing their interpretation.

The safety figures are descriptive counts and do not establish causation. Overall, the record supports a careful account of the observed group summaries and their uncertainty, while leaving important questions about analysis procedures, missing data, multiplicity, and clinical interpretation unresolved. No medical decision for an individual can be made from these registry summaries alone.

17. Why This Trial Matters Statistically

This trial is statistically informative because it presents a randomized placebo comparison for a continuous pain measure and reports both group summaries and an estimated between-group difference. The distinction between the change within each group and the difference between groups is essential: the mean change was negative in both groups, while the comparative estimate describes how far apart those group changes were.

The confidence interval adds information beyond a single point estimate. The estimate of 0.66 is accompanied by limits from 0.019 to 1.301, making clear that the plausible magnitude is not pinned down to one value. The interval’s proximity to zero at its lower end underscores why a point estimate or p-value alone is an incomplete account of uncertainty.

The registry also makes visible the difference between a continuous outcome and a threshold-based responder outcome. A mean summarizes the whole score scale, whereas a responder count depends on crossing a specified cutoff. Those approaches can yield different views of the same underlying outcome and should be interpreted on their own terms.

At the same time, the record highlights the importance of prespecification and transparent reporting. Multiple outcomes are listed, but multiplicity methods, detailed analysis populations, missing-data handling, and the statistical plan are not reported in the registry record. Without those details, unadjusted comparisons are best treated as descriptive statistical evidence rather than as a complete account of confirmatory inference. This distinction is particularly relevant when interpreting results near conventional significance thresholds.

The planning illustrations also demonstrate how assumed effect size and desired power affect sample-size requirements. They are distinct from the trial’s original design justification, which is not reported. Taken together, the estimates, uncertainty, and reporting gaps show why statistical interpretation depends not only on numerical results, but also on the design and analysis details available for evaluation.

18. 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.

Several limitations specific to this record affect interpretation. The primary outcome description labels the summary intent-to-treat, yet reports 79 Engensis participants while stating that 81 were randomized to that arm and that 2 were withdrawn before dosing. The record does not explain in detail how the analysis population was defined, or how any absent Day 180 measurements were handled. Placebo has 81 participants in the primary summary, but participant flow for endpoint availability is not reported.

The registry identifies the study as adaptive in its official title, but does not describe the adaptation rules, decision points, or their effect on the analysis. The original sample-size rationale is also not reported. The planning illustrations based on the observed effect cannot substitute for that information.

The primary and secondary p-values are unadjusted, while the record does not report multiplicity procedures or a hierarchy of hypotheses. The secondary analyses are not reported in the registry entries. The statistical model, any covariate adjustment, assumptions checks, and sensitivity analyses are not reported in the registry record either.

The group summaries do not reveal individual participant trajectories, and the record does not report a threshold for a clinically important difference on the pain scale. The listed safety counts lack detailed timing, event-level context, and causal assessments in the registry record. As a result, the estimates can be described statistically, but their clinical importance, robustness to analytic choices, and broader generalizability remain uncertain from this record alone.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study to Assess Safety and Efficacy of Engensis in Painful Diabetic Peripheral Neuropathy — NCT04469270.
• Registry record last updated 2025-10-09; status last verified 2025-08.
• Results first posted 2025-01-20.
• 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.

22. Record Summary

NCT04469270 is a completed randomized, parallel-group, placebo-controlled Phase 3 study of intramuscular Engensis in participants with painful diabetic peripheral neuropathy. The official title describes a double-blind, multicenter, adaptive study, and the registry reports quadruple masking. Enrollment was 162.

The primary outcome was change in average daily pain score from Day 0 to Day 180 on a 0 to 10 scale, where higher scores indicate worse pain. Mean changes were -2.03 for Engensis and -2.69 for placebo; the mean difference was 0.66, with a confidence interval from 0.019 to 1.301 and an unadjusted p-value of 0.044.

The record also includes secondary pain outcomes and descriptive safety counts. Multiplicity procedures, detailed missing-data methods, the original sample-size justification, and the statistical analysis plan are not reported in the registry record. Interpretation should therefore distinguish the posted estimates from unreported analysis details.