LYT-100 in Post-acute COVID-19 Respiratory Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for LYT-100 in Post-acute COVID-19 Respiratory Disease (NCT04652518), a randomized phase 2 study. The primary outcome is Change From Baseline in Distance Walked During the Six-Minute Walk Test (6MWT).

2. Clinical Question

3. Trial Design

NCT04652518 was a Phase 2 randomized, parallel-group study of deupirfenidone, also called LYT-100, in adults with post-acute COVID-19 respiratory disease. The registry lists PureTech as the sponsor, an enrollment of 185, a start date of 2020-12-11, a primary completion date of 2022-06-28, and a terminated status.

The study was organized in two parts. Part A was the randomized, double-blind comparison of LYT-100 with matching placebo. LYT-100 and placebo were taken orally twice a day for 91 days. Part B was an open-label extension for patients who completed Part A. The registry states that the extension was terminated after results of the double-blind portion; it does not give further details about the decision or its timing.

The design entries identify random allocation, a parallel model, and triple masking. The brief description characterizes Part A as double-blind. The registry does not specify the masking roles or provide further details that reconcile these descriptions. The posted primary outcome analysis compares the LYT-100 and placebo arms. The open-label extension is not a randomized placebo comparison and should not be read as another concurrent control arm.

The outcome entry describes an Intent to Treat analysis population and says it differs from the Safety Analysis Population. The posted arm sizes for the primary endpoint are 85.0 for placebo and 92.0 for LYT-100. Safety counts use different at-risk group sizes. These populations and denominators should not be treated as interchangeable. The original statistical plan, sample-size justification, allocation procedures, and detailed conduct of follow-up are not reported in the registry record.

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.

Double-blind (Days 1 to 91)

Reasons for not completing this period:

Open-label Extension (Days 92 to 182)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis based on the Intent to Treat (ITT) Population which is different from the Safety Analysis Population presented in the Participants Flow section. See Statistical Analysis Plan (SAP).

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: Information presented is based on the Intent to Treat (ITT) population which differs from the Safety Population presented in the participant flow. Please see Statistical Analysis Plan (SAP)

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Distance Walked During the Six-Minute Walk Test (6MWT), measured over Baseline to Day 91.

The primary endpoint was change from baseline to Day 91 in distance walked during the six-minute walk test, or 6MWT, measured in meters. In this test, a participant walks as quickly as possible on a flat, hard surface for six minutes. The recorded distance is a continuous measure, so the posted arm results are expressed as means rather than as counts of participants meeting a threshold.

The registry describes the 6MWT as a validated endpoint commonly used in clinical trial research. It is intended to reflect the global, integrated response of the systems involved during exercise. That makes walking distance a functional measure with contributions from more than one body system; it is not a direct measurement of a single physiological process.

The posted outcome is a change from baseline, not a Day 91 walking distance alone. The arm estimates are least-squares means, with standard errors reported as the dispersion measure: 48.77 meters for placebo and 44.28 meters for LYT-100. The registry does not provide a baseline walking distance in this outcome entry, and it does not report participant-level distributions. A mean describes the center of the modeled group result, but by itself does not show how individual responses varied.

7. Results Posted in the Registry

• LYT-100: mean 44.28 versus 48.77 on control; difference -4.49 (95% CI -32.13 to 23.15), standardized effect d = -0.05; z-test p = 0.750.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a change in walking distance measured in meters. The posted arm values are least-squares means, a type of modeled mean. The associated dispersion is reported as a standard error. A standard error describes the precision of an estimated mean, rather than the spread of individual participants’ measurements. The registry does not provide the individual observations or a standard deviation for each arm.

What does the mean difference represent?

The unadjusted recalculation subtracts the placebo mean from the LYT-100 mean. Using the posted values, the recalculated mean difference is -4.49 meters. A negative value indicates that the LYT-100 arm’s posted mean change is lower than the placebo arm’s posted mean change. The calculation is unadjusted: it compares the summary values without incorporating a model for baseline covariates or other adjustments. It is not a replacement for the sponsor’s mixed models analysis.

The recalculated standard deviation used for planning is approximate because the arm summaries report standard errors rather than standard deviations. The calculation is explicitly marked as using an approximate standard deviation. That approximation supports an illustrative planning calculation; it does not add information about the actual distribution of participants’ walking distances.

How should the p-values be understood?

The registry reports a p-value of 0.698 from a mixed models analysis. The model specification, covariates, handling of repeated measurements, and other analytic details are not reported in the registry record. The unadjusted recalculation gives p = 0.75 from the posted summary statistics. A p-value is a measure of data-model compatibility under a null hypothesis, conditional on the method’s assumptions. It does not measure the probability that one treatment is better, and it does not describe the magnitude or clinical importance of a difference.

The two p-values are not expected to be identical when they come from analyses with different methods. However, the information needed to account for their difference is not reported in the registry record. No discrepancy is flagged in the record. The mixed models result remains the sponsor’s reported analysis, while the recalculation is a separate, unadjusted check based on summary values.

What does a confidence interval add?

The recalculated 95% confidence interval for the mean difference runs from -32.13 to 23.15 meters. A confidence interval gives a range of values that are reasonably compatible with the data and calculation method. Its width conveys uncertainty: a wider interval indicates less precision than a narrower interval. Because this interval includes zero and values on both sides of zero, it does not narrowly identify the direction or size of the contrast. It is an unadjusted interval, not a reported interval from the mixed models analysis.

Confidence intervals depend on the analysis assumptions. Here, the recalculated interval is based on posted summary statistics and an approximate standard deviation. The registry does not give a confidence interval for the sponsor’s mixed models analysis. It is therefore important to distinguish the recalculated interval from a model-based interval that the sponsor did not post in this record.

Why can variability matter?

In general, greater variability in a continuous outcome makes it harder to distinguish a group mean difference from random variation. Over-dispersion is a general term for variability greater than a model expects. When present, it can make standard errors too small if the analysis fails to account for it, which can in turn make intervals too narrow and tests too optimistic. The registry does not report an over-dispersion assessment for this outcome. The approximate pooled standard deviation used for planning is 93.87 meters, but it is not an observed arm-specific standard deviation and should not be interpreted as one.

The 6MWT is an integrated functional measure, and individual performance can vary. A group mean and its standard error do not reveal the shape of the distribution, outliers, or whether responses cluster into subgroups. Those features cannot be assessed from the posted summary statistics alone.

What analysis details remain unknown?

The registry identifies the primary population as Intent to Treat and refers to a Statistical Analysis Plan, but the plan’s detailed methods are not reported in the registry record. The record does not report the model formula, covariate adjustments, assumptions for missing observations, sensitivity analyses, interim analyses, or the sponsor’s sample-size justification. It also does not report a multiplicity strategy. These omissions limit the extent to which an outside reader can reconstruct the sponsor’s analysis or assess its robustness.

Only one primary outcome measure and one analysis are listed, and no secondary outcomes are posted. That registry listing does not by itself establish how many outcomes or analyses were considered during trial conduct. Without the protocol and analysis plan details, the implications of selection among outcomes or analyses cannot be evaluated from this record.

10. Confidence Intervals and Precision

The recalculated contrast is -4.49 meters, with a 95% confidence interval from -32.13 to 23.15 meters. This interval is wide relative to the point estimate and includes zero. It therefore leaves substantial uncertainty about the direction and size of the mean difference. The estimate is not a precise statement that the true difference equals -4.49 meters; it is the center of a range of values compatible with this unadjusted calculation.

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the method used to construct it. A narrower interval indicates greater precision, while a wider interval indicates less. The interval is based on the posted summary statistics and an approximate standard deviation, rather than on a confidence interval reported for the sponsor’s mixed models analysis. The registry does not report an interval for that model-based result.

The posted standard errors are 9.997 meters for placebo and 9.948 meters for LYT-100. These describe uncertainty in each arm’s estimated mean, not the range of individual participant outcomes. The group means alone do not show how much participants varied or whether some experienced changes far from the mean.

Precision and clinical importance are different questions. The registry does not provide a threshold for a clinically important difference in 6MWT distance, so the interval cannot be classified against such a threshold from this record. The interval’s inclusion of values on both sides of zero indicates uncertainty about the direction of the contrast, but it does not prove that the arms are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess it; those details are not reported in the registry record.

11. 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 planning figures are participants per arm, not total event counts. The event-based convention for time-to-event outcomes does not apply to this continuous walking-distance endpoint. The figures illustrate the sample sizes that would be needed under stated planning assumptions for specified fractions of the observed effect; they are not the original trial’s design justification. The original design assumptions are not reported in the registry record.

The calculation assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It uses the observed effect as its starting point, with planning scenarios for 100%, 75%, and 50% of that effect. For 100% of the observed effect, the figures are 6,862 participants per arm for 80% power and 9,186 participants per arm for 90% power. For 75% of the observed effect, they are 12,199 participants per arm for 80% power and 16,330 participants per arm for 90% power. For 50% of the observed effect, they are 27,446 participants per arm for 80% power and 36,743 participants per arm for 90% power.

In general, 80% power means a planned study would have an 80% chance of detecting the specified effect under the assumptions if that effect were present. The 90% column uses a higher target probability and therefore requires more participants under these scenarios. Smaller effects are harder to distinguish from random variation, so the planning figures increase as the assumed effect becomes smaller. This is not observed power: it is a planning illustration based on the observed effect, not a measure of the trial’s achieved power.

12. 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 = -4.490; pooled standard deviation σ = 93.872.
2. n = 2 × (1.96 + 0.842)² × 93.872² / -4.490² = 6,861.5, rounded up to 6,862 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 <- -4.49                      # observed difference in means
sigma <- 93.8718707950364                     # 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(4652518)
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 = 6,862 (80% power), 9,186 (90% power)
 75% of observed effect: n per arm = 12,199 (80% power), 16,330 (90% power)
 50% of observed effect: n per arm = 27,446 (80% power), 36,743 (90% power)
power.t.test: 6862.4 
Simulated power at n = 6,862 per arm: 0.804 (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.

13. Analyses Reported by the Sponsor

The registry’s sponsor-reported result is a mixed models analysis with p = 0.698. It does not provide an estimate or confidence interval for that analysis. The separate recalculation from posted summary statistics gives a mean difference of -4.49 meters, a 95% confidence interval from -32.13 to 23.15 meters, and an unadjusted p-value of 0.75.

The recalculation uses the two posted arm means and standard errors and is not a recreation of the mixed models analysis. The registry does not report enough detail about the sponsor’s model to reproduce it or explain the difference between the p-values. The sponsor’s result should therefore be understood as the reported model-based analysis, while the recalculation is a transparent but limited, unadjusted comparison of the posted summaries. Neither p-value alone conveys the size or precision of the effect; the recalculated estimate and interval provide that information for the unadjusted contrast.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, time points, or analyses are tested. In general, conducting many tests can increase the chance of observing a small p-value even when there is no underlying effect. Statistical plans may address this through prespecified testing hierarchies or adjustments, but the appropriate approach depends on the design and the questions being tested.

The registry lists one outcome measure and one analysis, and no secondary outcome measures are posted. It does not report a multiplicity procedure, a testing hierarchy, or whether other outcomes or analyses were considered. The absence of those details means multiplicity handling cannot be assessed from the registry record. It should not be assumed either that adjustment was made or that no multiplicity concerns existed.

The outcome description identifies the Intent to Treat population and notes that it differs from the Safety Analysis Population. It refers to the Statistical Analysis Plan, but details of population definitions and analysis implementation are not reported in the registry record. The primary endpoint group sizes are 85.0 for placebo and 92.0 for LYT-100, while the safety at-risk group sizes are 90, 95, and 107 across placebo, LYT-100, and the open-label extension. These are different analysis contexts and should not be combined or treated as if they represented the same set of observations.

The registry does not report how missing 6MWT measurements were handled, whether any imputation was used, or whether sensitivity analyses evaluated missing-data assumptions. In general, missing outcome data can affect an estimate if the probability of being observed is related to the outcome or treatment assignment. The impact depends on why measurements are missing and on the analysis assumptions. Those reasons and assumptions are not reported in the registry record, so the robustness of the primary result to missing data cannot be determined from the posted information.

The registry also does not report interim analyses or stopping rules. The study status is terminated, and the open-label extension is described as terminated after results of the double-blind portion. The record does not explain whether the primary analysis involved any interim decision or provide details about the termination decision. No inference about those processes is supported by the available registry entries.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 (1.1%), intervertebral disc protrusion (1.1%), abdominal pain (1.1%), pneumonia (1.1%), appendicitis (1.1%).

The safety record reports serious adverse events for 3 participants among 90 at risk in the placebo group, 3 among 95 at risk in the LYT-100 group, and 4 among 107 at risk in the open-label extension group. Deaths are reported as 1 in the placebo group, 0 in the LYT-100 group, and 0 in the extension group. The record lists other adverse events affecting 19 participants in placebo, 52 in LYT-100, and 41 in the extension; these are distinct from the serious-event counts in the safety summary.

The open-label extension is a separate treatment context and is not a randomized comparison with placebo. Its counts should not be interpreted as if they came from a third randomized arm. The registry does not provide exposure-adjusted event rates, detailed follow-up time for these safety groups, or enough information to compare risk while accounting for duration of exposure. Counts alone also do not establish whether an event was caused by the treatment.

The serious-event terms listed include COVID-19, intervertebral disc protrusion, abdominal pain, pneumonia, appendicitis, and mixed dementia, each reported as 1.1%. The registry record does not provide further context in this entry for interpreting these terms or their relationship to treatment.

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

The posted primary endpoint results describe modeled mean changes in six-minute walk distance from baseline to Day 91. The placebo estimate was 48.77 meters and the LYT-100 estimate was 44.28 meters. The unadjusted recalculated contrast was -4.49 meters, with a 95% confidence interval from -32.13 to 23.15 meters. Those data leave uncertainty about both the direction and size of the difference.

The registry’s mixed models analysis reports p = 0.698. This p-value does not establish that the treatments are equivalent, and it does not give the probability that any hypothesis is true. Equivalence would require a prespecified margin and a suitable analysis, neither of which is reported in the registry record. Likewise, the result should not be described as proof of benefit or lack of benefit. It is a statistical result for the posted outcome, population, and analysis.

The recalculated confidence interval is an unadjusted interval based on posted summary statistics, not the interval from the sponsor’s mixed models analysis. It includes zero and extends to values on both sides of zero. The registry does not provide a threshold for a clinically important 6MWT change, so the clinical importance of values within that interval cannot be judged from this record alone.

The findings also do not resolve questions about other outcomes, longer-term results, or other populations. No secondary outcome measures are posted. The record’s termination status and its note that the open-label extension ended after results of the double-blind portion do not, without further information, explain why the study ended or what that decision means for the primary estimate. The posted result should be interpreted as evidence with limited precision and incomplete analytic detail, not as a definitive statement about treatment effects beyond this trial’s recorded comparison.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate and its uncertainty should be read together. The unadjusted mean difference is -4.49 meters, but the 95% confidence interval extends from -32.13 to 23.15 meters. The estimate gives a concise direction and magnitude for the contrast, while the interval shows that the posted summary data do not determine that contrast precisely. Reporting only the p-value would leave out that central information.

It also demonstrates the importance of distinguishing a sponsor’s model-based analysis from a recalculation using summary statistics. The registry reports a mixed models p-value of 0.698, whereas the unadjusted recalculation gives p = 0.75. The results should not be substituted for each other: the model details are not reported, and the recalculation cannot reproduce them. This distinction helps readers avoid treating a summary-based check as a full reanalysis.

The sample-size illustrations show how planning depends on the effect chosen for detection. In general, planning for a smaller effect requires more participants to achieve a chosen power target under the same assumptions. Because the calculations use the observed effect and stated simplifying assumptions, they are not a substitute for the trial’s original design rationale, which is not reported in the registry record.

Finally, this record makes clear that outcome, safety, and analysis populations may use different denominators and that an open-label extension is not equivalent to a randomized comparator. Careful interpretation depends on keeping those distinctions, the endpoint’s time frame, and the limits of the reported methods in view.

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.

The registry reports the primary endpoint as a least-squares mean with a standard error for each arm, but does not provide participant-level measurements or arm-specific standard deviations. The recalculated standard deviation is approximate, limiting how fully the unadjusted analysis can represent the underlying outcome distribution. The registry also does not provide a confidence interval for the sponsor’s mixed models analysis.

Key details of the sponsor’s statistical model are not reported in the registry record. The model specification, covariate adjustments, handling of repeated measures, missing-data methods, and sensitivity analyses are unavailable in the posted entry. The reference to a Statistical Analysis Plan does not supply those methods. The difference between the mixed models p-value and the unadjusted recalculated p-value therefore cannot be resolved from the record.

The record does not report the original sample-size justification, interim analyses, stopping rules, or multiplicity approach. It lists no secondary outcomes, which limits assessment of outcome breadth from this entry. It also does not give a clinically important threshold for the 6MWT outcome, so the clinical meaning of the estimated difference and its interval cannot be classified using a trial-specific benchmark.

The primary outcome and safety analyses use different populations and denominators. The registry says the Intent to Treat population differs from the Safety Analysis Population, but detailed population rules are not reported. Safety counts for the open-label extension come from a non-randomized treatment context and cannot be read as a third randomized comparison. Event counts alone do not account for exposure duration or establish causation.

The study is listed as terminated, and the open-label extension was terminated after results of the double-blind portion. The registry does not report the reason for termination or further details about its consequences. These limitations mean the posted record supports a bounded interpretation of the primary comparison, not a complete reconstruction of trial conduct.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: LYT-100 in Post-acute COVID-19 Respiratory Disease — NCT04652518.
• Registry record last updated 2026-06-23; status last verified 2026-05.
• Results first posted 2026-06-23.
• 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

NCT04652518 was a Phase 2 randomized, parallel-group trial of LYT-100 versus matching placebo in adults with post-acute COVID-19 respiratory complications. Part A used twice-daily treatment for 91 days; Part B was an open-label extension that was terminated after results of the double-blind portion. The registry lists an enrollment of 185 and a terminated status.

The primary endpoint was change from baseline to Day 91 in six-minute walk distance. Posted least-squares mean changes were 48.77 meters for placebo and 44.28 meters for LYT-100. The registry reports a mixed models p-value of 0.698. An unadjusted recalculation gives a mean difference of -4.49 meters and a 95% confidence interval from -32.13 to 23.15 meters. The interval indicates substantial uncertainty, and the registry does not report the sponsor model’s estimate or confidence interval.

Important details about the statistical plan, missing data, multiplicity, and termination are not reported in the registry record. The posted result should be understood in light of those limitations and the distinction between the randomized comparison, the open-label extension, and the separate safety analysis population.