Study to Compare Efficacy and Safety of CT-P42 in Comparison With Eylea in Patients With Diabetic Macular Edema: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Compare Efficacy and Safety of CT-P42 in Comparison With Eylea in Patients With Diabetic Macular Edema (NCT04739306), a randomized phase 3 study. The primary outcome is Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8.

2. Clinical Question

3. Trial Design

The registry describes a randomized, active-controlled, double-masked, parallel-group Phase 3 study of CT-P42 and Eylea in patients with diabetic macular edema. The masking field is recorded as triple. The trial is marked completed, with enrollment of 348. Celltrion is named as the sponsor. The recorded start date is 2021-07-22, and primary completion is dated 2022-10-14.

Participants were assigned to one of the two biological interventions. The arm descriptions do not provide further details about treatment schedules, dose, or administration, and those details are not reported in the registry record. The primary outcome was assessed at Week 8. Secondary outcomes include BCVA change at Week 52, the proportion gaining at least 15 ETDRS letters, the proportion with at least a 2-step improvement in diabetic retinopathy severity score, and change in central subfield thickness assessed by optical coherence tomography.

The planned enrollment and the analysis denominators are not identical. The primary outcome lists 169 participants for CT-P42 and 172 for Eylea, while the outcome population is described as the full analysis set of randomized participants receiving at least 1 full dose during the Main Study Period. The reasons for the difference between those outcome counts and total enrollment are not reported in the registry record. The record also does not report the original sample-size justification, the detailed randomization procedure, treatment duration, or a full protocol description. Those missing details limit what can be inferred about the trial’s design choices beyond the features explicitly recorded.

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.

Before assignment: Subjects who were randomly assigned to either group administrated study drug by intravitreal injection (IVT) via a sigle-dose vial every 4 weeks for 5 doses, then every 8 weeks for 4 doses up to Week 48. After the Main Study period, a total of 31 subjects, regardless of the treatment group in Main Study Period, were enrolled in a 4-week open-label, single-arm Extension study. The subjects were administrated 2 mg/0.05mL of CT-P42 by pre-filled syringe IVT injection at Extension Week 0 (1 dose).

Main Study Period

Reasons for not completing this period:

CT-P42 PFS (Extension Study Period)

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) consists of all subjects who are randomly assigned and received at least 1 full dose of study drug during the Main Study Period. Missing data were not imputed unless methods for handling missing data are specified.

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 Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 8, measured over Baseline and Week 8.

The primary endpoint is mean change from baseline in best corrected visual acuity at Week 8, measured using ETDRS letters. The registry explains that visual acuity was assessed with ETDRS charts and that a higher score represents better functioning. The endpoint therefore captures change in a standardized measure of visual acuity, rather than a count of events or a time until an event occurs.

A mean change compares the average follow-up score with the baseline score within each treatment group. The between-group comparison then estimates how much the average change differs between CT-P42 and Eylea. A continuous outcome retains the scale of the letter score, so the estimated difference is expressed in letters and can be interpreted alongside its uncertainty interval. The reported primary group estimates are least-squares means, which come from the sponsor’s stated ANCOVA analysis; the registry does not describe the model covariates.

The outcome description specifies eligibility based on a study-eye BCVA ETDRS letter score of 73 to 34 at Screening and Day 1. The registry’s primary population includes randomized participants who received at least 1 full dose during the Main Study Period. The endpoint is clinically interpretable as a change in measured visual acuity, but statistical interpretation still depends on the comparison between groups, the analysis population, missing-data handling, and precision. Detailed endpoint-assessment procedures beyond those stated are not reported in the registry record.

7. Results Posted in the Registry

• Eylea: mean 8.85 versus 9.43 on control; difference -0.58 (95% CI -2.76 to 1.60), standardized effect d = -0.06; z-test p = 0.602.

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.

Mean Change From Baseline in BCVA at Week 52

• 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:
  • Eylea: mean 11.10 versus 12.10 on control; difference -1.00 (95% CI -3.09 to 1.09), standardized effect d = -0.11; z-test p = 0.348.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Eylea and the control. The interval gives the range of effects that remain compatible with the data.

Proportion of Subjects Who Gained ≥15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52

• 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:
  • Eylea: 29.7% (52/175) versus 34.7% (60/173) on control; risk difference -5.0 percentage points (95% CI -14.8 to 4.8), risk ratio 0.86 (0.63–1.16); unadjusted two-proportion z-test p = 0.321.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Eylea and the control. The interval gives the range of effects that remain compatible with the data.

Proportion of Subjects With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52

• 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:
  • Eylea: 21.7% (38/175) versus 23.7% (41/173) on control; risk difference -2.0 percentage points (95% CI -10.8 to 6.8), risk ratio 0.92 (0.62–1.35); unadjusted two-proportion z-test p = 0.658.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Eylea and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes provide a broader set of visual and retinal measures at Week 52. They include average BCVA change, the proportion with a gain of at least 15 ETDRS letters, the proportion with at least a 2-step improvement in DRSS, and change in central subfield thickness. The posted numerical results for the first three outcomes are available, while a result for the central subfield thickness outcome is not reported in the registry record.

Across the posted secondary comparisons, the estimates do not present a consistent, precise separation between groups. The continuous visual-acuity estimate is relatively close to zero on its letter scale, and the categorical estimates have intervals spanning zero. This broad pattern is compatible with uncertainty about the size and direction of the group differences. The secondary findings do not overturn or independently confirm the primary Week 8 result; they address different outcomes and a later assessment time.

Secondary endpoints are often examined as a family of questions. If many comparisons are tested, the chance of obtaining at least one apparently notable result by chance can increase. General statistical explanation: multiplicity procedures can control that risk, but the registry does not report an adjustment strategy for these secondary analyses. Their posted p-values are unadjusted, so they should carry less inferential weight than a prespecified primary analysis with a clearly stated testing plan. The registry record does not report whether a hierarchical testing procedure or another multiplicity plan was used.

The outcome-specific analysis populations also differ in size. That affects the precision of the secondary estimates and means they should not be assumed to represent exactly the same set of participants as the primary analysis. Because endpoint-level missing-data handling and multiplicity details are not reported in the registry record, the secondary outcomes are best read as supportive descriptive evidence rather than as a collection of independent confirmatory tests.

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

• Mean Change From Baseline in BCVA at Week 52
• Proportion of Subjects Who Gained ≥15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52
• Proportion of Subjects With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52
• Change From Baseline in Central Subfield Thickness (CST) at Week 52 as Assessed on Optical Coherence Tomography (OCT)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: each participant has a BCVA letter score, and the outcome is change from baseline. The registry reports least-squares means and standard errors for the two groups, alongside an ANCOVA analysis of the difference in least-squares means. A least-squares mean is a model-based group estimate; its exact interpretation depends on the model and any covariates. The registry does not identify the ANCOVA covariates or give the complete model specification.

What does the mean difference represent?

A mean difference expresses the contrast between two group averages on the outcome’s original scale. In the unadjusted recalculation, the comparison is Eylea relative to CT-P42, so the estimate is -0.58 letters. In the sponsor’s reported analysis, the estimated difference is 0.58, consistent with CT-P42 relative to Eylea. Reversing the order of a two-group contrast reverses its sign but does not change the underlying separation between the group estimates. The interpretation should therefore state the order of comparison rather than treating a sign by itself as a treatment advantage.

The recalculation uses posted group means, sample sizes, and standard errors. Its pooled standard deviation is marked as approximate, which is relevant because the primary group summaries report standard errors rather than standard deviations. A standard error describes uncertainty in an estimated mean, not the spread of individual participant scores. General statistical explanation: standard deviations describe variation among observations, while standard errors describe the precision of a sample estimate. Recovering a standard deviation from a standard error requires assumptions about the summary data, so the resulting pooled value is an approximation in this primary comparison.

How should the interval and p-value be read?

A confidence interval gives a range of values reasonably compatible with the data and the specified analysis, under its assumptions. Here the recalculated interval extends from -2.76 to 1.6 for the Eylea-minus-CT-P42 contrast. Since it includes zero, it is compatible with no difference as well as with differences in either direction. The unadjusted p-value of 0.602 describes the data’s compatibility with a null difference under the recalculation’s assumptions; it is not the probability that the null hypothesis is true, nor a measure of clinical importance.

The sponsor reports a 90% confidence interval for its ANCOVA contrast, from -0.52 to 1.67, and classifies the analysis as equivalence. Equivalence is assessed by comparing an interval with a prespecified range of differences considered acceptably small. The margin is not reported in the registry record, so the basis for the equivalence classification cannot be reconstructed from the posted result alone. The sponsor’s interval and the recalculated interval also reflect different analyses and are not direct substitutes for one another.

Why can over-dispersion matter?

General statistical explanation: for count outcomes, over-dispersion means that observed variation exceeds what a simple model assumes. It can make standard errors too small and intervals too narrow if not handled appropriately. The primary endpoint is continuous, not a count, and no over-dispersion analysis is reported or needed to describe the posted mean comparison. The categorical secondary outcomes are proportions, for which the uncertainty depends on event counts and denominators; those outcomes should be interpreted using their own intervals rather than the continuous-outcome model.

What does the analysis population mean?

The stated full analysis set consists of all participants who were randomized and received at least 1 full dose during the Main Study Period. The primary endpoint counts are 169 for CT-P42 and 172 for Eylea. The registry notes that missing data were not imputed unless methods for handling missing data are specified. A detailed missing-data method is not reported in the registry record. The posted denominator and the stated population definition matter because estimates apply to the participants included in that analysis, and missing observations can affect both precision and the interpretation of group comparisons.

The registry’s methods information is therefore partial: it identifies the ANCOVA method and estimand type for the sponsor’s primary analysis, but not its covariates, missing-data details, or equivalence margin. The unadjusted recalculation offers a separate descriptive check, not a replacement for the sponsor’s formal model.

11. Confidence Intervals and Precision

Precision is reflected in the width of an uncertainty interval: narrower intervals generally indicate more precise estimates, while wider intervals allow a broader range of effects compatible with the data. The recalculated primary difference is -0.58 letters for Eylea relative to CT-P42, with an interval from -2.76 to 1.6. That range includes zero and also includes values on either side of zero, so the recalculation does not pin down the direction of a small difference precisely.

The sponsor’s ANCOVA estimate is 0.58 for the contrast in the opposite direction, with a 90% confidence interval from -0.52 to 1.67. This interval also includes zero. The interval level differs from the one conventionally associated with many unadjusted recalculations, but the registry explicitly labels the sponsor interval as 90%; a confidence level for the recalculated interval is not stated in the record. The models, contrast direction, and interval limits differ, so the intervals should be read in the context of their respective analyses rather than compared as if they were generated identically.

The Week 52 mean-change interval, from -3.089 to 1.089 for Eylea relative to CT-P42, likewise spans zero. For the categorical secondary outcomes, the risk-difference intervals also cross zero: -0.148 to 0.048 for gaining at least 15 letters, and -0.108 to 0.068 for at least a 2-step DRSS improvement. These intervals show uncertainty about the size and direction of group differences; they do not establish that the groups are identical.

Precision depends on both the variability of the measured outcomes and the amount of information in the analysis. The primary group counts are 169 and 172, and the observed standard errors are 0.798 and 0.775. The registry does not report a target precision or the original design assumptions used to select enrollment. Thus, the intervals describe precision of the posted estimates, but the record does not establish what degree of precision was intended in the original design.

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 figures are planning illustrations based on the observed effect, not the trial’s original design calculation. For these continuous and binary outcomes, the figures are participants per arm, not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The original sample-size assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm estimated to give an 80% chance of detecting the chosen effect under those planning assumptions, if that effect is the true one and the assumptions hold. The 90% power column gives the corresponding planning count for a 90% chance. These are design-planning quantities, not guarantees about any particular study. For the primary endpoint, the illustration ranges from 4,921 participants per arm when planning for 100% of the observed effect to 19,682 participants per arm when planning for 50% of the observed effect at 80% power. At 90% power, the corresponding listed figures are 6,588 and 26,349.

The same direction applies across the listed effect fractions: planning to detect a smaller effect requires more participants. For example, planning for 75% of the observed effect requires more participants per arm than planning for 100% of the observed effect. The figures are conditional illustrations using the observed estimate as a reference; they do not establish what the trial was designed to detect or what its original assumptions were. This is not observed power.

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 = -0.580; pooled standard deviation σ = 10.269.
2. n = 2 × (1.96 + 0.842)² × 10.269² / -0.580² = 4,920.5, rounded up to 4,921 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 <- -0.58                      # observed difference in means
sigma <- 10.2686224339132                     # 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(4739306)
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 = 4,921 (80% power), 6,588 (90% power)
 75% of observed effect: n per arm = 8,748 (80% power), 11,711 (90% power)
 50% of observed effect: n per arm = 19,682 (80% power), 26,349 (90% power)
power.t.test: 4921.4 
Simulated power at n = 4,921 per arm: 0.797 (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. Analyses Reported by the Sponsor

The sponsor’s primary analysis is reported as ANCOVA, with an estimated difference in least-squares means of 0.58 and a 90% confidence interval from -0.52 to 1.67. The registry classifies this as an equivalence analysis. No p-value is posted for that analysis, and the equivalence margin is not reported in the registry record. Without the margin, the registry result alone does not show how the reported interval was evaluated against the prespecified equivalence criterion.

The unadjusted recalculation uses the posted group summaries and gives an Eylea-minus-CT-P42 difference of -0.58, with an interval from -2.76 to 1.6 and p = 0.602. Its contrast direction is reversed relative to the sponsor estimate, so the sign differs while the numerical point estimates represent the same separation in opposite directions. The recalculation is not the sponsor’s ANCOVA model and does not include any model adjustment.

The sponsor’s analysis is the registry’s formal reported analysis and should be treated as primary when interpreting the trial’s own statistical conclusion. The recalculation is a supplementary unadjusted check, useful for understanding the posted group-level data but not a substitute for the sponsor’s model. Their intervals should not be directly equated because the analysis methods and stated confidence level differ.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome and four secondary outcomes. The primary outcome is mean change in BCVA at Week 8. Secondary outcomes include BCVA change at Week 52, a gain of at least 15 letters, at least a 2-step improvement in DRSS, and central subfield thickness change. The number of posted outcome measures is five, and one analysis is listed for the primary outcome. The statistical plan for controlling multiplicity across the primary and secondary outcomes is not reported in the registry record.

Multiplicity matters because interpreting several tests as if each were the only test can make chance findings more likely across the full set of questions. General statistical explanation: a prespecified hierarchy, family-wise error procedure, or other planned approach can define how evidence is assessed across multiple endpoints. The record does not report whether such a procedure was planned or used. Consequently, the secondary p-values should be treated as unadjusted, and their evidential strength is limited when considered alongside several outcomes.

The primary endpoint description defines the full analysis set as all randomized participants who received at least 1 full dose of study drug during the Main Study Period. The primary outcome counts are 169 for CT-P42 and 172 for Eylea. The registry states that missing data were not imputed unless methods for handling missing data are specified. It does not report detailed rules for handling missing Week 8 measurements, the extent or reasons for missingness, or a sensitivity analysis for missing outcomes.

Different secondary endpoints have their own posted denominators, and the registry does not explain all differences between those counts and enrollment. It also does not report whether missing-data handling was consistent across outcomes. These gaps matter because complete-case estimates can be affected if missingness is related to outcome or treatment assignment. No particular missing-data mechanism or bias can be inferred from the registry record alone.

The record also does not report the original sample-size justification, interim-analysis plan, or complete statistical analysis plan. Those items should not be inferred from the planning illustrations or from the posted analysis summaries.

16. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure (1.1%), death (1.1%), cholecystitis (1.1%), diabetic foot (1.1%), diabetic ulcer (1.1%).

For the Main Study Period, serious adverse events are reported for 19 of 174 participants in the CT-P42 group and 17 of 174 in the Eylea group. Other adverse events are reported for 64 of 174 and 71 of 174, respectively. The registry also lists 3 deaths for CT-P42 and 2 for Eylea during the Main Study Period. These are descriptive counts; the record does not provide a comparative statistical analysis of these safety results.

During the Extension Study Period, the CT-P42 group lists 31 participants at risk, 0 with a serious adverse event, 3 with other adverse events, and 0 deaths. No Eylea extension-period group is listed in the posted safety information. The extension group count and its duration are not described further in the registry record, so the extension figures should not be treated as directly comparable with the Main Study Period figures.

The listed serious adverse-event terms include cardiac failure, death, cholecystitis, diabetic foot, and diabetic ulcer, each reported as 1.1%, and deficiency anaemia, reported as 0.6%. The registry’s safety summaries do not establish causation, relative risk, or whether differences between groups are statistically meaningful. Counts should be read in relation to the at-risk group sizes and the period represented, while recognizing that additional event definitions and adjudication details are not reported in the registry record.

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

The posted primary results describe average change in BCVA at Week 8 in the analyzed groups. CT-P42 has a least-squares mean change of 9.43 letters and Eylea 8.85 letters. The sponsor’s ANCOVA contrast is 0.58, with a 90% confidence interval from -0.52 to 1.67; the unadjusted recalculation expresses the contrast in the opposite direction and gives -0.58, with an interval from -2.76 to 1.6. Both intervals include zero, so neither estimate precisely establishes a difference in one direction.

The sponsor labels its analysis as equivalence, but the equivalence margin is not reported in the registry record. An equivalence conclusion depends on a predefined acceptable range and whether the appropriate interval lies within that range. The posted interval and label do not reveal that margin. It is therefore not possible to independently assess the equivalence criterion from the registry record alone.

These results do not establish that the interventions are identical. Failure to identify a precise difference is not the same as proof of no difference; the interval remains compatible with a range of possible effects. Nor do the results, by themselves, establish clinical importance. Statistical estimates describe group averages and uncertainty under specified analyses, while clinical interpretation also depends on relevant thresholds and context not reported in the registry record.

The posted safety counts describe events observed during specified periods, but they do not establish whether an event was caused by an intervention or whether apparent count differences are meaningful. The secondary results concern additional outcomes and are subject to uncertainty and unreported multiplicity handling. The most defensible reading is limited to the estimates, intervals, denominators, and analysis labels recorded, without extending them to claims about individual outcomes or treatment decisions.

18. Why This Trial Matters Statistically

This trial is statistically notable because it combines an active-controlled randomized comparison with a continuous primary endpoint and a sponsor-reported equivalence analysis. These features make the definition and direction of the contrast important. A signed mean difference is meaningful only when its ordering is clear; the sponsor and the unadjusted recalculation express the contrast in opposite directions.

It also illustrates why a point estimate should not be read alone. The primary estimates are close in scale, but uncertainty intervals extend across zero. The sponsor’s equivalence label raises a distinct question from testing whether a difference is nonzero: equivalence requires a specified margin and an interval evaluated against that margin. That margin is not reported in the registry record, so the label cannot be independently checked using the posted information.

The record offers useful but incomplete information about analysis populations and methods. It defines the full analysis set and identifies ANCOVA for the sponsor’s primary result, but does not provide covariates, detailed missing-data handling, or multiplicity procedures. These omissions show why registry outcomes should be read together with analysis methods, not as isolated estimates.

Finally, the sample-size illustrations show how planning counts depend on the effect one aims to detect and the desired power, under stated assumptions. They are not the original trial design calculation. Keeping this distinction clear prevents a retrospective planning illustration from being mistaken for the study’s planned enrollment rationale or a measure of observed power.

19. 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 gives a limited description of the treatment regimens: the interventions are named, but arm descriptions are blank and details such as dosing and administration are not reported. The trial’s randomization and masking labels are present, but the sequence-generation and concealment procedures are not reported in the registry record. The masking field is recorded as triple, while the official title describes the study as double-masked; the record does not explain this difference.

The sponsor’s primary analysis is identified as ANCOVA, but the model covariates and full specification are not reported. The equivalence margin is also not reported, preventing independent assessment of the sponsor’s equivalence classification. The recalculated result is an unadjusted calculation from summary statistics and does not reproduce the sponsor’s model.

The registry provides no detailed account of missing observations, reasons for missingness, endpoint-specific imputation, or sensitivity analyses. It states that missing data were not imputed unless handling methods are specified, but does not provide a detailed method. The original sample-size justification, interim analyses, and multiplicity strategy are not reported in the registry record. The planning illustrations are based on observed effects and should not be taken as evidence of the original design rationale.

Some outcome denominators vary, and the record does not explain all reasons for those differences. The Week 52 central subfield thickness result is not reported in the registry record. Safety summaries are counts without a comparative statistical analysis, and the extension-period safety information lists only a CT-P42 group. These limits constrain interpretation of cross-outcome and cross-period comparisons.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study to Compare Efficacy and Safety of CT-P42 in Comparison With Eylea in Patients With Diabetic Macular Edema — NCT04739306.
• Registry record last updated 2023-12-05; status last verified 2023-09.
• Results first posted 2023-12-05.
• 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.

23. Record Summary

NCT04739306 is a completed, randomized, active-controlled, parallel-group Phase 3 study of CT-P42 versus Eylea in patients with diabetic macular edema. Enrollment is 348, and Celltrion is named as the sponsor. The primary outcome is mean change from baseline in BCVA at Week 8, measured in ETDRS letters.

The sponsor reports an ANCOVA estimated difference in least-squares means of 0.58, with a 90% confidence interval from -0.52 to 1.67, and classifies the analysis as equivalence. The equivalence margin is not reported in the registry record. An unadjusted recalculation gives an Eylea-minus-CT-P42 difference of -0.58, with an interval from -2.76 to 1.6 and p = 0.602. The secondary results cover additional visual and retinal outcomes; multiplicity and detailed missing-data procedures are not reported. Safety counts are presented for the Main Study Period and a CT-P42 Extension Study Period.