Suprachoroidal Injection of CLS-TA Alone or With Aflibercept in Subjects With Diabetic Macular Edema: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Suprachoroidal Injection of CLS-TA Alone or With Aflibercept in Subjects With Diabetic Macular Edema (NCT02949024), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events.

2. Clinical Question

The central statistical question is descriptive: how many participants in each treatment arm were recorded as having adverse events during follow-up? The registry reports no serious adverse events in either arm, alongside counts in the other adverse-event category. These counts are useful for characterizing what was observed in this study, but they do not by themselves show whether one regimen is safer than the other. Non-randomized allocation and the different arm descriptions limit a direct comparison, while the open-label design can affect the reporting or assessment of events.

3. Trial Design

This was an open-label study with non-randomized allocation and a parallel-arm model. It included TX Naïve and Previous TX arms. The registry lists the study as phase 1 and phase 2, with enrollment of 20, and records its status as completed. The recorded study start date is 2016-11-10, and the primary completion date is 2017-10-17.

The treatment regimens differed by arm. The TX Naïve Arm received one unilateral injection of intravitreal aflibercept in combination with one unilateral injection of suprachoroidal CLS-TA in the same eye. The Previous TX Arm received one unilateral injection of suprachoroidal CLS-TA. The registry gives 10 participants at risk for serious adverse events and 10 at risk for other adverse events in each arm. These arm-specific denominators should be read as reported, not as evidence that treatment assignment was randomized or that the groups were otherwise comparable.

Because allocation was non-randomized, the treatment groups may differ in ways that influence outcomes. The arm labels and regimens also indicate different treatment histories and different treatment combinations. Consequently, any contrast between the observed counts is descriptive, not a controlled estimate of the effect of adding aflibercept or of CLS-TA alone. Open-label conduct means treatment assignment was not masked; the registry does not report further details on event assessment or safeguards against assessment bias.

The primary outcome concerns participants with treatment-emergent adverse events and serious adverse events over 6 months of follow-up. The registry lists secondary outcomes for mean change from baseline in intraocular pressure, mean change from baseline in central subfield thickness, best corrected visual acuity, and CLS-TA injections. The posted results summarized for this analysis concern adverse-event counts. Details of the protocol, analysis procedures, and results for the other outcomes 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety population included all subjects who received study treatment.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The Intent-to-treat population included all subjects who received study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events, measured over Over 6 months of follow-up.

The primary endpoint is the number of participants with treatment-emergent adverse events and serious adverse events reported over 6 months of follow-up. Its stated unit is participants, and the safety population includes all subjects who received study treatment. This is a count-based safety endpoint: it describes how many participants were recorded as having events, rather than the total number of event episodes or the severity of every event.

Such an endpoint is used to characterize safety and tolerability during the study. Counting affected participants can make the occurrence of adverse events understandable at the group level, while serious adverse events are considered separately because their seriousness is clinically important. The registry’s figures distinguish serious adverse events from other adverse events, and also report deaths. These categories should not be conflated: a count of participants with other adverse events is not a count of serious adverse events.

The endpoint does not by itself establish causation. The registry describes events reported during follow-up, but the available record does not specify how investigators judged whether an event was caused by treatment. Nor does a participant count convey event timing, duration, recurrence, or severity beyond the serious-event classification. Those details are not reported in the registry record. The counts therefore support a focused description of the recorded safety experience, not a complete characterization of every aspect of tolerability.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary safety outcome is a binary participant-level measure summarized as counts: a participant either was or was not recorded in an event category during the relevant follow-up. The registry states that the endpoint covers treatment-emergent adverse events and serious adverse events over 6 months. The reported arm-specific figures give the number at risk and the number affected for serious events and other adverse events. They also give deaths. No inferential analyses are reported for these outcomes.

What does a participant count represent?

A participant count answers how many people in an arm experienced an event category, not how many individual event episodes occurred. One person could experience more than one event, but the participant-level count does not reveal that history. It also does not convey when events occurred, how long they lasted, or their severity beyond the serious-event classification. The record does not report those details. The counts should therefore be interpreted as a concise summary, not a complete event-level account.

Because the endpoint is binary at the participant level, analysts might in general describe it using proportions, compare groups using a risk difference or relative measure, or fit a model suited to binary outcomes. These are general methodological possibilities, not analyses reported for this study. No such estimates or tests are reported in the registry record, and no additional values should be inferred from the posted counts.

Why does the design matter for comparison?

Random allocation, when used, can help balance measured and unmeasured participant characteristics between treatment groups on average. This study was non-randomized. Its arms also represent different treatment regimens and treatment-history categories. As a result, an unadjusted contrast would not isolate a treatment effect: differences could be related to baseline characteristics or other factors as well as treatment. The record does not report an adjustment strategy or an analysis intended to address confounding.

The study was open-label, so participants and study personnel were not masked to treatment assignment according to the registry. In general, knowledge of assignment can influence reporting, observation, or assessment of outcomes, particularly for outcomes that rely on judgment. The registry does not describe event-adjudication procedures or masking of safety assessors. It is therefore not possible to determine from this record whether or how the study addressed potential assessment bias.

What does uncertainty add?

General explanation: an estimate based on a limited study population is subject to sampling variability. A confidence interval describes uncertainty around an estimate under the assumptions of its statistical method. A p-value, when used, describes how compatible the observed data are with a specified null model; it does not measure the size or importance of an effect. Neither type of statistic is reported for the adverse-event counts in the registry record. The counts alone cannot establish a precise population-level rate or show that the arms differ.

For rare outcomes, a zero observed count can coexist with nonzero underlying risk. That is a general statistical point, not an estimate for this study. The registry’s zero serious adverse-event counts should be interpreted as no such events recorded in the stated groups during the reported follow-up, rather than as evidence that the possibility of serious events has been ruled out.

What is known about the analysis plan?

The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or methods for handling missing data. The study’s phase designation and enrollment do not by themselves reveal the intended power or precision of the safety estimates. Sample-size planning illustrations, when presented, are distinct from observed power: they describe hypothetical design requirements under specified assumptions, not the probability that a completed study has detected an effect. The record does not report the trial’s own design justification or enough information to assess the assumptions behind any planning illustration.

The safety population is defined as all subjects who received study treatment. That definition identifies who is included for the safety outcome, but the record does not explain how missing follow-up, incomplete event reporting, or withdrawal was handled. It also does not report whether all participants completed the stated follow-up. Those omissions matter because participant counts depend on event ascertainment and the opportunity to observe events.

The registry lists other outcomes, including changes in intraocular pressure and central subfield thickness, best corrected visual acuity, and CLS-TA injections. The statistical methods and numerical results for those outcomes are not reported in the registry record. Accordingly, no conclusion about their estimates, uncertainty, or analysis can be drawn from the adverse-event counts.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary safety outcome and secondary outcomes concerning intraocular pressure, central subfield thickness, best corrected visual acuity, and CLS-TA injections. When a study evaluates multiple outcomes or multiple time points, the chance of at least one apparently notable result can increase if each is tested separately without an appropriate strategy. This is a general statistical concern. The registry record does not report a multiplicity plan, a hierarchy for testing outcomes, or which outcomes were intended to support formal claims.

The record reports no analyses for the listed outcomes. It does not provide p-values or confidence intervals for the adverse-event counts, nor does it describe inferential testing for secondary outcomes. In the absence of a reported analysis plan, it is not possible to determine whether multiplicity was considered or whether any adjustment was applied.

The safety population included all subjects who received study treatment. This is the population specified for the endpoint, but the record does not describe missing-data procedures, withdrawals, incomplete follow-up, or the completeness of adverse-event ascertainment. It also does not state how participants with partial follow-up were handled. These details are important when interpreting event counts because absence of a recorded event is not necessarily equivalent to complete observation without an event.

The record does not report protocol deviations, analysis exclusions, or sensitivity analyses for missing data. These aspects of the analysis are therefore not reported in the registry record. The posted counts can be described as recorded for the stated safety population, but the available information is insufficient to assess the impact of incomplete data or the handling of multiple outcomes.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event figures are 0 of 10 participants at risk in the TX Naïve Arm and 0 of 10 in the Previous TX Arm. The reported death count is 0 in each arm. These figures mean that no serious adverse events or deaths were recorded in the respective groups during the reported follow-up. They do not establish that the underlying risk is zero.

The registry also reports other adverse-event counts: 8 of 10 participants at risk in the TX Naïve Arm and 9 of 10 in the Previous TX Arm. These figures are separate from the serious adverse-event counts. The record does not provide the specific event terms in the serious category; the list of top serious terms is empty. No further event descriptions or severity details are reported in the registry record.

These counts are descriptive. The study was non-randomized, open-label, and the arms received different regimens and had different treatment-history labels. The counts therefore should not be read as a controlled safety comparison or as evidence that one regimen caused more events. The endpoint covers 6 months of follow-up, and broader or longer-term safety cannot be inferred from these figures.

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

The registry reports a small, descriptive safety experience for a completed phase 1 and phase 2 study of suprachoroidal CLS-TA alone or with intravitreal aflibercept in subjects with diabetic macular edema. The primary safety endpoint counted participants with treatment-emergent adverse events and serious adverse events during 6 months of follow-up. The reported serious-event counts were 0 of 10 in each arm, and deaths were 0 in each arm. Other adverse-event counts were 8 of 10 and 9 of 10, respectively.

These observations describe what was recorded in the study; they do not demonstrate that either treatment is safe or unsafe in a broader population. A zero count does not eliminate the possibility of an event outside the observed participants or follow-up. Likewise, the other adverse-event counts do not establish that the events were caused by treatment, and the registry does not give event-level details needed to characterize their nature or severity.

The two arms do not provide a randomized head-to-head comparison. Allocation was non-randomized, the regimens differed, and the arm labels indicate different treatment-history categories. Thus, differences in observed counts cannot be attributed solely to the treatment components. No adjusted comparison, confidence interval, or significance test is reported in the registry record.

The record lists additional outcomes involving intraocular pressure, central subfield thickness, best corrected visual acuity, and CLS-TA injections, but the results for those outcomes are not reported in the registry record. The posted adverse-event counts do not answer whether either regimen changed those outcomes. Overall, the results support a limited description of the reported safety observations, not a definitive comparative conclusion about efficacy or safety.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of why design determines what can be concluded from observed outcomes. The registry reports adverse-event counts for two treatment arms, but allocation was non-randomized and the regimens were not identical. A numerical difference between arm counts, by itself, would not separate treatment effects from differences in participant characteristics, treatment history, or other factors.

The study also illustrates the distinction between event counts and inferential evidence. Counts can clearly describe what was observed in the safety population, including the reported absence of serious adverse events. They do not provide uncertainty estimates or establish that the underlying risk is absent. Without reported confidence intervals, tests, or a statistical model, precision and comparative uncertainty cannot be assessed from the registry record.

Finally, the study’s focus on safety and tolerability should be kept distinct from its listed efficacy-related outcomes. The record names measures involving intraocular pressure, central subfield thickness, and visual acuity, but does not report their results in the information analyzed. Recognizing that distinction prevents descriptive safety figures from being used to make claims they cannot support. The record is most useful when read as a bounded report of observed events, with explicit attention to non-randomized allocation, open-label conduct, and unreported analysis details.

14. 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 design limits causal interpretation. Allocation was non-randomized, and the TX Naïve Arm and Previous TX Arm differed both in treatment regimen and in treatment-history label. The arms are not a like-for-like control comparison. No adjusted analysis is reported in the registry record, so observed differences cannot be separated from potential differences in participant characteristics or other factors.

The study was open-label. The registry does not report whether adverse events were assessed by masked reviewers, how events were adjudicated, or whether event attribution to treatment was assessed using prespecified criteria. These details would help readers judge the potential for differences in reporting or assessment.

The primary endpoint covers 6 months of follow-up, and the posted safety summary gives participant counts rather than detailed event histories. The record does not report individual event terms for the serious-event category, timing, duration, recurrence, or severity details beyond the classification as serious. Longer-term observations are not reported in the registry record.

The registry does not report confidence intervals, p-values, adjusted comparisons, a statistical analysis plan, sample-size justification, interim analyses, or multiplicity procedures. It also does not describe missing-data handling, withdrawals, completion of follow-up, or sensitivity analyses. These omissions prevent a fuller assessment of precision, analysis choices, and the effect of incomplete observation.

Although several secondary outcomes are listed, their results and methods are not reported in the registry record. The available safety counts therefore cannot support conclusions about those outcomes or about comparative efficacy.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Suprachoroidal Injection of CLS-TA Alone or With Aflibercept in Subjects With Diabetic Macular Edema — NCT02949024.
• Registry record last updated 2021-05-13; status last verified 2021-04.
• Results first posted 2021-04-19.
• 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.

18. Record Summary

The registry record describes a completed, open-label, non-randomized parallel study of suprachoroidal CLS-TA alone or with intravitreal aflibercept for diabetic macular edema. It lists phase 1 and phase 2, enrollment of 20, a start date of 2016-11-10, and a primary completion date of 2017-10-17.

The TX Naïve Arm received one unilateral injection of intravitreal aflibercept with one unilateral injection of suprachoroidal CLS-TA in the same eye. The Previous TX Arm received one unilateral injection of suprachoroidal CLS-TA. The primary endpoint counted participants with treatment-emergent adverse events and serious adverse events over 6 months of follow-up.

The registry reports no serious adverse events or deaths in either arm; other adverse-event counts were 8 of 10 and 9 of 10. These are descriptive findings, not a randomized treatment comparison. Analysis details and results for the listed secondary outcomes are not reported in the registry record.