A Clinical Effectiveness Study Examining the Efficacy and Safety of ONS-5010 in Subjects With Neovascular Age-related Macular Degeneration (AMD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Effectiveness Study Examining the Efficacy and Safety of ONS-5010 in Subjects With Neovascular Age-related Macular Degeneration (AMD) (NCT03834753), a randomized phase 3 study. The primary outcome is Proportion of Subjects Who Gain 15 or More Letters in Best Corrected Visual Acuity (BCVA).

2. Clinical Question

The study asked whether the proportion of participants gaining at least 15 letters in best corrected visual acuity differed between ONS-5010, identified in the registry record as bevacizumab, and ranibizumab. Visual acuity was assessed using letters read on Early Treatment Diabetic Retinopathy Study charts. The primary assessment timeframe was 11 months.

This question concerns a defined visual-acuity response threshold rather than every possible change in vision. A participant who gains at least 15 letters meets the endpoint definition; the endpoint does not by itself describe the size of gains beyond that threshold or changes in other aspects of eye health. The registry also lists secondary visual-acuity measures, including mean change and other letter-gain thresholds. The interpretation of those outcomes is distinct from the primary comparison and depends on their own results and analysis details.

3. Trial Design

The registry describes a completed phase 3, randomized, double-masked, parallel-group study. Its official title characterizes it as multicenter. The study compared ONS-5010, listed as bevacizumab, with ranibizumab in participants with subfoveal choroidal neovascularization secondary to age-related macular degeneration. The registry enrollment is 228. The recorded start date is 2019-06-25, and the primary completion date is 2021-06-07.

Random assignment is intended to create comparison groups that are not systematically chosen by participants or investigators. Double masking is intended to limit the influence of knowing the assigned treatment on care, outcome assessment, or reporting. Those design features describe the stated trial design; details of how randomization and masking were implemented are not reported in the registry record. The record also does not report the allocation ratio or the exact masking procedures.

The primary outcome is reported for 108 participants in the bevacizumab group and 104 in the ranibizumab group. The registry enrollment and outcome counts refer to different recorded quantities; participant flow, exclusions, and the analysis population are not reported in the registry record. The safety summaries use different at-risk group sizes, 113 for bevacizumab and 115 for ranibizumab. These counts should be read in the context of their respective outcome records rather than treated as interchangeable denominators.

The registry describes the study objective as comparing ONS-5010 with ranibizumab for safety and effectiveness in participants with AMD. It does not report the original sample-size justification, detailed protocol, interim analyses, or full statistical analysis plan. The available results therefore support description of the recorded group outcomes and their unadjusted comparisons, but do not establish how every design or analysis decision was prespecified.

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

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 Proportion of Subjects Who Gain 15 or More Letters in Best Corrected Visual Acuity (BCVA), measured over 11 months.

The primary endpoint is the proportion of participants who gained 15 or more letters in best corrected visual acuity at 11 months. Visual acuity was assessed as letters read using Early Treatment Diabetic Retinopathy Study charts. The registry notes that a positive change represents an improvement in visual acuity.

This is a binary endpoint: each participant either meets the specified letter-gain threshold or does not. The resulting group proportion describes how commonly that threshold was reached among participants included in the recorded outcome. It is not the same as the mean change in letters, which uses the magnitude of each participant's change, nor does it capture gains that fall short of the threshold as continuous changes.

A threshold-based outcome can be clinically interpretable because it focuses on the frequency of a defined degree of improvement. However, reducing a range of changes to whether a threshold was crossed loses information about the size and distribution of changes within each category. The registry also lists mean change and other visual-acuity thresholds as secondary outcomes, which can add context but do not replace the primary endpoint.

The registry record reports the primary endpoint at 11 months and gives group counts and denominators. It does not report further details about the timing of assessments within that timeframe, missing endpoint observations, or the analysis population definition. Those omissions limit how fully the endpoint result can be connected to participant follow-up and the original analysis plan.

7. Results Posted in the Registry

• Ranibizumab: 23.1% (24/104) versus 41.7% (45/108) on control; risk difference -18.6 percentage points (95% CI -30.9 to -6.3), risk ratio 0.55 (0.37–0.84); unadjusted two-proportion z-test p = 0.004.

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 in the Best Corrected Visual Acuity

• 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:
  • Ranibizumab: mean 5.80 versus 11.20 on control; difference -5.40 (95% CI -9.18 to -1.62), standardized effect d = -0.40; z-test p = 0.005.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ranibizumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Proportion of Participants Who Gain at Least 10 Letters in the Best Corrected Visual Acuity

• 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:
  • Ranibizumab: 34.6% (36/104) versus 56.5% (61/108) on control; risk difference -21.9 percentage points (95% CI -34.9 to -8.8), risk ratio 0.61 (0.45–0.84); unadjusted two-proportion z-test p = 0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Ranibizumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Proportion of Participants Who Gain at Least 5 Letters in the Best Corrected Visual Acuity

• 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:
  • Ranibizumab: 51.0% (53/104) versus 68.5% (74/108) on control; risk difference -17.6 percentage points (95% CI -30.6 to -4.6), risk ratio 0.74 (0.59–0.93); unadjusted two-proportion z-test p = 0.009.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Ranibizumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover several related views of visual acuity: average letter change, participant counts reaching 10-letter and 5-letter gains, loss of fewer than 15 letters, and acuity of 20/200 or worse. Numerical results are posted for mean change and the two gain thresholds. For the remaining listed outcomes, numerical results are not reported in the registry record.

Across the secondary outcomes with numerical results, the unadjusted comparisons point in the same direction as the primary result: the recorded outcomes are higher in the bevacizumab group than in the ranibizumab group. This coherent direction adds descriptive context, but these measures are related and may reflect overlapping participants and the same underlying visual-acuity experience. They should not be counted as separate, independent confirmations of the primary comparison.

Secondary findings generally carry less inferential weight when many outcomes are examined without a reported plan for controlling multiplicity. Each additional comparison creates another opportunity for a statistically unusual result, while unadjusted p-values and intervals do not account for that broader set of questions. The registry record does not report a multiplicity strategy or identify a hierarchy for interpreting the secondary outcomes. That absence does not erase the posted estimates, but it makes them more appropriate as supportive descriptive evidence than as stand-alone confirmatory findings.

The mean change and threshold outcomes also answer different questions. An average can reflect the size of changes across participants, while a threshold proportion describes how many reached a particular cutoff. Agreement in direction across such measures can help characterize the pattern, but it does not resolve uncertainty about missing outcomes, analysis populations, or the prespecified status of each comparison.

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

• Mean Change in the Best Corrected Visual Acuity
• Proportion of Participants Who Gain at Least 10 Letters in the Best Corrected Visual Acuity
• Proportion of Participants Who Gain at Least 5 Letters in the Best Corrected Visual Acuity
• Proportion of Participants Who Lose Fewer Than 15 Letters in the Best Corrected Visual Acuity
• Proportion of Participants With Visual-acuity Snellen Equivalent of 20/200 or Worse

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary because it records whether each participant crossed a prespecified letter-gain threshold. For such an outcome, a group proportion is the number meeting the endpoint divided by the number included in that group’s reported endpoint data. The registry posts the event counts and denominators for both groups. The comparison uses a risk difference, which expresses the difference between the two group proportions on the probability scale.

What does the sign of the risk difference mean?

The comparison is oriented as ranibizumab relative to bevacizumab. A negative risk difference means the recorded proportion in the ranibizumab group is lower than the recorded proportion in the bevacizumab group. The sign is not an intrinsic label of benefit or harm: it depends on which group is subtracted from which. For the primary endpoint, the estimate is -0.186. Its confidence interval is -0.309 to -0.063. These are unadjusted re-calculations from the posted summary statistics, rather than an adjusted model estimate.

What does a confidence interval convey?

In general, a confidence interval describes the range of effect values compatible with the data under a specified statistical method. It reflects sampling uncertainty and is not a range containing a fixed proportion of individual participant outcomes. An interval that includes zero is compatible with no group difference under the method; an interval entirely on one side of zero indicates that the corresponding unadjusted comparison is inconsistent with zero at the confidence level used. The primary interval lies below zero. Confidence intervals do not account for unreported sources of bias, missing data, or selection among multiple outcomes.

What does the p-value add?

In general, a p-value measures how unusual data at least as discrepant as those observed would be under a specified null hypothesis and test assumptions. It does not provide the probability that the null hypothesis is true, nor does it measure the size or practical importance of an effect. The primary unadjusted p-value is 0.004. The registry does not report whether an adjustment for multiple comparisons was prespecified or applied, so the value should not be treated as multiplicity-adjusted.

How should secondary outcomes be read?

The mean-change endpoint summarizes average letter change, whereas the threshold outcomes classify participants according to whether they achieved a specified gain. The mean-change comparison is reported as a mean difference of -5.4 letters for ranibizumab relative to bevacizumab, with a 95% confidence interval from -9.175 to -1.625 and an unadjusted p-value of 0.005. The mean and threshold measures describe related but non-identical features of the outcome distribution. They should not be treated as independent replications, because they concern visual acuity in the same trial and may use overlapping participants.

For binary outcomes, the risk difference is one way to express a contrast. General alternatives include a risk ratio or odds ratio, which express relative rather than absolute comparisons. The registry also posts relative measures for the primary and some secondary binary outcomes. Each measure has a different interpretation, and choosing among them does not change the underlying event counts. The risk difference is useful for describing the absolute scale of the group contrast, while relative measures compare proportions in ratio form.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when observed variation is greater than a statistical model assumes. If a model underestimates variation, its standard errors can be too small and its intervals too narrow. The registry's listed primary endpoint is a participant-level binary outcome, and the posted comparison is not described as a model incorporating over-dispersion. The registry record does not report additional model diagnostics or an adjusted analysis that would allow such features to be assessed.

The registry includes no separately reported analysis entries for the outcomes described in the record. Therefore, the comparisons available for interpretation are the posted group summaries and their unadjusted contrasts. Details such as covariate adjustment, stratification, missing-data methods, and analysis-population rules are not reported in the registry record. These methods can affect estimates and uncertainty, so absence of those details limits assessment of whether the posted calculations match the original prespecified analysis.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data estimate a group contrast. For the primary risk difference, the estimate for ranibizumab relative to bevacizumab is -0.186, and its 95% confidence interval extends from -0.309 to -0.063. The interval does not include zero, but it spans a range of possible contrasts rather than identifying a single exact value. The result therefore supports a directional unadjusted difference in these recorded data while leaving uncertainty about its precise magnitude.

Confidence intervals are general statistical summaries of sampling uncertainty under the method used. They do not capture every uncertainty relevant to a trial: unreported missingness, departures from the analysis plan, measurement issues, and multiplicity can affect how a result should be interpreted. The registry record does not provide enough information to assess those sources in detail.

The secondary mean-change comparison has a reported 95% confidence interval from -9.175 to -1.625 letters for ranibizumab relative to bevacizumab. The binary secondary comparisons also have intervals that exclude zero in their posted unadjusted calculations. These intervals describe each outcome separately; they do not correct for examining multiple outcomes.

Precision also depends on the number of participants contributing to an outcome and on variation in the measurements. The registry reports different group denominators for the primary, mean-change, and safety outcomes. It does not report participant flow or the reasons those denominators differ. Consequently, the posted sample counts help contextualize the estimates but cannot alone explain the source of missingness or establish whether it could influence precision or bias.

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 planning figures are participants per arm, not total events. The posted planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each illustration targets a stated fraction of the observed effect. The registry record does not report the trial’s original sample-size justification or design assumptions; these figures are planning illustrations based on the observed results, not the trial’s own design calculations.

For the primary endpoint, planning for 100% of the observed effect gives 99 participants per arm for 80% power and 132 participants per arm for 90% power. Planning for 75% of the observed effect gives 182 participants per arm for 80% power and 243 participants per arm for 90% power. Planning for 50% of the observed effect gives 423 participants per arm for 80% power and 566 participants per arm for 90% power.

In general, power is the chance that a study will detect an effect of a specified size under the assumptions used for planning, if that effect is present. The 80% and 90% columns describe different target probabilities for detecting the assumed effect, not probabilities that the observed result is true. The 90% target generally requires more participants than the 80% target for the same assumed effect. Smaller effects need more participants to detect, which is why planning for a smaller fraction of the observed effect yields larger per-arm figures.

These values are not observed power. They are forward-looking illustrations, and their relevance depends on whether the planning assumptions are reasonable for a future study. The original trial’s own sample-size rationale is not reported in the registry record.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.417; treatment proportion p₁ = 0.231; average p̄ = 0.324.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6617 = 1.2969.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6485 = 0.5458.
4. n = (1.2969 + 0.5458)² / (-0.1859)² = 98.3, rounded up to 99 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
p0 <- 0.416666666666667                          # control proportion
p1 <- 0.230769230769231                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(3834753)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 99 (80% power), 132 (90% power)
 75% of observed effect: n per arm = 182 (80% power), 243 (90% power)
 50% of observed effect: n per arm = 423 (80% power), 566 (90% power)
power.prop.test: 98.3 
Simulated power at n = 99 per arm: 0.808 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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

Multiplicity arises when several outcomes or comparisons are tested. In general, examining more statistical hypotheses increases the chance that at least one result will appear unusual by chance if all null hypotheses are true. Methods such as prespecified outcome hierarchies or adjustment procedures can address this issue, but the registry record does not report whether any such method was planned or used. The listed secondary outcomes should therefore be read as separate unadjusted results rather than as a family of multiplicity-controlled tests.

The record identifies a primary endpoint and lists secondary visual-acuity outcomes, but it does not report a complete statistical analysis plan, the order in which secondary outcomes were tested, or a family-wise error strategy. The primary result is more central to the stated question than the secondary comparisons, but the lack of analysis-plan detail limits assessment of how confirmatory the reported p-values are.

Missing-data handling is also not reported. The registry gives endpoint denominators for the primary and secondary outcomes and different at-risk counts for safety, but it does not provide a participant-flow account explaining these counts. It does not state how absent measurements were handled, whether participants were excluded from an analysis, or whether sensitivity analyses were conducted. The impact of missingness depends on why data are missing and how they were treated; those details cannot be inferred from the posted group summaries.

The analysis populations are not described in sufficient detail to determine whether the results use an intention-to-treat population, a per-protocol population, or another defined set. Randomization is a design feature, but the way participants are included in analysis matters for preserving the comparability created by random assignment. The registry record also does not report covariate adjustment, stratification, or interim-analysis details. These are limitations in reporting, not evidence that a particular method was or was not used.

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 5% 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 (0.9%), aortic valve stenosis (0.9%), bundle branch block (0.9%), myocardial infarction (0.9%), death (0.9%).

The registry records serious adverse events for 14 of 113 participants in the bevacizumab group and 16 of 115 in the ranibizumab group. Other adverse events are recorded for 31 of 113 and 34 of 115, respectively. Deaths are recorded for 3 participants in the bevacizumab group and 2 in the ranibizumab group. These are counts within the safety group sizes posted for each arm; they should not be confused with the denominators used for the primary visual-acuity endpoint.

The registry lists acute myocardial infarction, aortic valve stenosis, bundle branch block, myocardial infarction, death, and COVID-19 among the top serious-event terms, each reported as 0.9%. The record does not provide enough detail to establish the timing, duration, severity beyond the serious-event classification, or relationship of each event to study treatment. Nor do the counts alone establish whether group differences are attributable to treatment or chance.

Safety summaries are descriptive. Differences in counts should be interpreted with attention to the number at risk, event definitions, follow-up, and completeness of reporting. Detailed event-level analyses and causal attribution are not reported in the registry record.

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

The posted results describe a randomized comparison of two study groups on visual-acuity outcomes and adverse events. For the primary endpoint, the recorded proportion meeting the 15-letter gain threshold was higher in the bevacizumab group than in the ranibizumab group, and the unadjusted risk-difference interval lies below zero when expressed as ranibizumab relative to bevacizumab. This is a statement about the observed trial data and the specified endpoint at 11 months.

The result does not by itself establish why the groups differed, how the result would generalize to people outside the trial, or whether the same contrast would be observed under different follow-up or analysis procedures. The registry record does not report the complete protocol, analysis populations, missing-data handling, or multiplicity strategy. Those omissions matter when judging how securely the estimates reflect the intended randomized comparison.

A statistically unusual result is not automatically a measure of clinical importance. The primary endpoint records whether participants crossed a threshold, while mean letter change and other visual-acuity outcomes provide different perspectives. The confidence interval communicates uncertainty in the primary contrast, but does not capture all limitations of the record. The listed secondary comparisons are unadjusted, and numerical results for two listed visual-acuity outcomes are not reported.

The safety counts are descriptive records of events in the groups. They do not alone establish causal relationships or settle comparative safety. Likewise, the registry entry does not provide a basis for advice to an individual participant. The most defensible reading is limited to the outcomes, denominators, uncertainty estimates, and reporting details documented in the record.

17. Why This Trial Matters Statistically

This trial illustrates how a binary clinical endpoint can make a study question accessible while also compressing information. The primary measure asks whether participants reached a defined letter-gain threshold. That supports a clear comparison of proportions, but it does not show the full distribution of visual-acuity changes. The accompanying mean-change and other threshold outcomes address related aspects of the same clinical measure.

It also illustrates why the contrast’s direction and scale should be stated explicitly. The risk difference is oriented as ranibizumab relative to bevacizumab, so its negative sign corresponds to a lower recorded endpoint proportion in the ranibizumab group. A risk difference is an absolute comparison, while relative measures answer a different question. Clear labeling prevents a sign from being mistaken for an outcome direction independent of group ordering.

Precision is central to interpretation. The primary confidence interval excludes zero in the posted unadjusted calculation, yet still spans a range of possible differences. Statistical significance alone does not describe the estimate’s precision or resolve limitations that confidence intervals do not cover. The registry’s lack of detail on missing data, analysis populations, and multiplicity leaves important questions about the full inferential context unanswered.

Finally, the entry separates planning illustrations from trial design evidence. Sample-size figures based on observed effects can help readers understand how assumptions about effect size and power influence participant requirements, but they do not reveal the original design rationale. Keeping those distinct prevents retrospective planning calculations from being mistaken for prespecified design features or observed power.

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 record does not report the original sample-size justification, the full protocol, or a detailed statistical analysis plan. It therefore does not establish the assumptions used to design the trial, the planned handling of interim analyses, or the intended hierarchy among secondary outcomes. The planning illustrations based on observed effects should not be mistaken for those original decisions.

Participant flow and analysis populations are not described in enough detail to explain why the primary outcome denominators are 108 and 104 while the registry enrollment is 228, or why the safety groups use at-risk counts of 113 and 115. The reasons for differing outcome denominators, exclusions, and missing observations are not reported in the registry record. Without this information, the potential influence of missingness or analysis-set selection cannot be assessed.

The available comparisons are unadjusted, and no multiplicity procedure is reported. The secondary outcomes are related measures of visual acuity and should not be treated as independent evidence. Numerical results for the listed outcomes concerning loss of fewer than 15 letters and visual acuity of 20/200 or worse are not reported in the registry record.

Safety reporting is also limited to group counts and listed serious-event terms. Details of event timing, attribution, and event-level follow-up are not reported. These limitations concern what can be assessed from the registry entry; they do not establish that unreported procedures or analyses were absent from the conduct of the study.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Clinical Effectiveness Study Examining the Efficacy and Safety of ONS-5010 in Subjects With Neovascular Age-related Macular Degeneration (AMD) — NCT03834753.
• Registry record last updated 2026-08-03; status last verified 2026-07.
• Results first posted 2026-08-03.
• 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

NCT03834753 is a completed phase 3 randomized, double-masked, parallel-group study comparing ONS-5010, listed as bevacizumab, with ranibizumab in participants with neovascular age-related macular degeneration. The registry lists enrollment of 228 and identifies the primary endpoint as the proportion gaining at least 15 letters in best corrected visual acuity at 11 months.

The posted primary group counts are 45 of 108 for bevacizumab and 24 of 104 for ranibizumab. The unadjusted risk difference for ranibizumab relative to bevacizumab is -0.186, with a 95% confidence interval from -0.309 to -0.063 and an unadjusted p-value of 0.004. Secondary visual-acuity results with numerical data generally follow the same direction. Safety counts are descriptive, and important details about participant flow, missing-data methods, analysis populations, and multiplicity are not reported in the registry record.