Safety and Exploratory Efficacy Study of SF0166 in the Treatment of Neovascular Age-Related Macular Degeneration (AMD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Exploratory Efficacy Study of SF0166 in the Treatment of Neovascular Age-Related Macular Degeneration (AMD) (NCT02914639), a randomized phase 1, phase 2 study. The primary outcome is Number of Subjects With No Cells Observed Following Slit Lamp Examination From Baseline to Week 8.

2. Clinical Question

The study is identified as a Phase I/II randomized trial in people with neovascular AMD. Its stated purpose was to evaluate safety and exploratory efficacy of topical SF0166. The clinical question is therefore about both safety and exploratory observations, rather than a definitive comparison against placebo or usual care: the listed arms differ by SF0166 dose, and no other comparator is recorded.

The primary outcome is assessed at multiple visits: baseline, Week 2, Week 4, Week 6 and Week 8. A secondary outcome is change in best-corrected visual acuity (BCVA) from baseline (Day 0) at Week 4 and Week 8. The registry names these outcomes but does not provide their results in the information available for this analysis. Accordingly, the stated question can be described, but the magnitude, direction and precision of any observed difference between doses cannot be determined from the registry record.

3. Trial Design

This was a randomized, parallel-group Phase I/II study of SF0166 Topical Ophthalmic Solution in neovascular (wet) AMD. The registry lists an enrollment of 44 and describes two dose groups: SF0166 low dose 2.5% BID and SF0166 high dose 5.0% BID. Both regimens were instilled in the study eye twice daily for 28 days of treatment. A placebo or no-treatment arm is not reported in the registry record, so the listed treatment contrast is between the two SF0166 doses.

The masking description is not consistent within the record. The official title calls the study double-masked, while the trial-design field labels masking quadruple. The record does not explain this difference or specify which people were masked. It is therefore appropriate to report both descriptions without resolving the discrepancy. The study is also described as multicenter in its official title.

The recorded start date is 2016-10-05, and the primary completion date is 2017-06-26. The study status is completed. OcuTerra Therapeutics, Inc. is listed as the sponsor. The registry describes the study's purpose as evaluating safety and exploratory efficacy; it does not provide a protocol-based explanation of the dose selection or a sample-size justification.

The primary outcome was the number of participants with no cells observed following slit-lamp examination. Its listed timeframe spans baseline and follow-up visits through Week 8. The secondary outcome concerns change in BCVA at Week 4 and Week 8 relative to Day 0. There are 17 outcome measures listed, but no outcome analyses are listed. No statistical analysis plan or results comparing the randomized groups is 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 analysis population includes all randomized participants, 23 in the low dose 2.5% group and 21 in the high dose 5.0% group. One participant in the high dose 5.0% group discontinued prior to Week 2 and one participant in the high dose group discontinued prior to Week 6.

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 Number of Subjects With No Cells Observed Following Slit Lamp Examination From Baseline to Week 8, measured over Baseline, Week 2, Week 4, Week 6 and Week 8.

The primary endpoint is described as the number of participants with no cells observed following slit-lamp examination from baseline to Week 8. The registry further defines the measure as the number and percentage of subjects with no red blood cell counts in the anterior chamber. It is assessed at baseline, Week 2, Week 4, Week 6 and Week 8. Thus, it is a repeated categorical observation: at each listed visit, a participant is described according to whether the stated finding is present.

In general, a finding of no cells is used as a clinical examination measure, while repeated assessment can describe how that finding is observed across follow-up. The registry does not state the clinical rationale for selecting this endpoint, how observations at different visits were combined into a primary comparison, or whether a particular visit was designated as the main analysis time point. Those details are not reported in the registry record.

The outcome is a count of participants, not a continuous measurement such as a change in visual-acuity score. The record gives the randomized group sizes and notes discontinuations in the high-dose group, but it does not provide the endpoint counts or percentages at any visit. Without those values, the endpoint's observed frequency and any difference between dose groups cannot be described. The listed secondary visual-acuity outcome is distinct from this primary examination measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to treatment groups according to a chance-based process. In general, this can reduce systematic differences between groups at the time of assignment, although it does not guarantee that groups are identical, particularly in a small study. Here, the registry identifies randomized allocation and two active dose regimens. It does not describe the randomization sequence, allocation concealment, or any stratification factors. Those implementation details are not reported in the registry record.

What does a parallel-group design mean?

In a parallel design, participants are assigned to a group and receive that group's assigned regimen during the study, rather than switching between regimens in a crossover sequence. The record lists a low-dose and a high-dose SF0166 group, each treated BID for 28 days. This structure makes the dose groups the relevant randomized comparison. The record does not list a placebo group, so the design as recorded does not support a direct SF0166-versus-placebo comparison.

What does masking mean?

Masking is intended, in general, to limit the influence of treatment knowledge on care, assessment or reporting. The registry's official title describes the trial as double-masked, while its design field says quadruple masking. Since the record does not reconcile these descriptions or identify who was masked, the masking implementation cannot be specified more precisely. This is a reporting ambiguity, not evidence that masking was or was not maintained.

How should the primary outcome be understood statistically?

The primary outcome counts participants with no cells observed following slit-lamp examination, and the registry describes the finding as no red blood cell counts in the anterior chamber. It is recorded at several visits from baseline through Week 8. A count of participants is a discrete outcome, and the corresponding percentage expresses that count relative to an analysis denominator. In general, a group comparison for a categorical outcome may be expressed using a difference, ratio or model-based contrast, but the registry does not report which measure or statistical model was used. It also does not report the endpoint values needed to calculate or interpret any such contrast.

Repeated visits create an additional analysis choice. In general, an analysis might compare groups at a particular visit, describe each visit separately, or model the pattern across visits while accounting for repeated observations from the same participant. These approaches answer different questions and can use different assumptions. The registry provides the visit schedule but does not say how the visits were combined, which visit was designated for a primary test, or whether within-participant correlation was modeled.

What do uncertainty intervals and p-values convey?

In general, a confidence interval communicates uncertainty around an estimate under the assumptions of the method used. A narrow interval indicates greater precision than a wide interval, while an interval that includes a null value may be compatible with a range of effects. A p-value describes how unusual data at least as incompatible with a specified null hypothesis would be under the test's assumptions; it does not measure the probability that a treatment works or that the null hypothesis is true. No confidence interval, p-value, or test result for the primary outcome is reported in the registry record, so these concepts cannot be applied to a numerical dose-group estimate.

Exploratory outcomes can be useful for describing patterns and informing later questions, but exploratory status does not itself determine whether an observed difference is reliable. Interpretation still depends on the analysis plan, outcome definitions, missingness and precision. The registry states that efficacy was exploratory and identifies a secondary BCVA outcome, but does not report the analysis methods or results for it.

Why do multiple outcomes and visits matter?

When many outcomes, time points or comparisons are examined, the chance of finding at least one apparently notable result can increase if each is assessed separately without accounting for the set of tests. In general, multiplicity procedures can control or otherwise address that concern, but they may affect the interpretation and precision of individual comparisons. The record lists 17 outcome measures and several visits for the primary outcome. It does not report whether multiplicity was addressed, which outcomes were considered confirmatory, or how comparisons were prioritized. No adjustment method should be inferred.

What can a planning illustration tell a reader?

In general, sample-size planning asks how many participants would be needed for a chosen design to detect an effect of a specified size under stated assumptions. The planning assumptions described for illustrations use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of an observed effect. Such illustrations are not the trial's original sample-size justification and are not observed power. The registry does not report the protocol's sample-size rationale. Because no primary endpoint effect is reported and the endpoint is not reduced to a single comparison, a planning illustration cannot be treated as a direct test of the trial's primary question.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is assessed at baseline, Week 2, Week 4, Week 6 and Week 8, and the record lists 17 outcome measures overall. Multiple outcomes and visits can create multiple opportunities for comparisons. In general, prespecifying a primary comparison and an approach to multiplicity helps readers distinguish confirmatory tests from exploratory analyses. The registry record does not report whether any multiplicity adjustment was planned or performed, how the primary visit or contrast was selected, or how outcomes were prioritized.

The registry describes the primary analysis population as all randomized participants, with 23 in the low-dose group and 21 in the high-dose group. It notes that one participant in the high-dose group discontinued before Week 2 and one participant in that group discontinued before Week 6. These discontinuations do not by themselves establish which outcome observations were missing or how they were treated analytically. Visit-specific denominators, reasons for discontinuation, and missing-data methods are not reported in the registry record.

In general, an analysis of all randomized participants aims to retain participants in their assigned groups, while other analysis populations may require specified levels of treatment exposure or outcome availability. The record identifies an all-randomized primary population, but does not describe additional analysis populations, the handling of protocol deviations, or whether participants were analyzed according to assigned dose. The registry lists no outcome analyses, so it is not possible to determine how the stated population was applied to the results.

Interim analyses, stopping rules, and sensitivity analyses are also not reported in the registry record. Their presence or absence should not be inferred from the completed status of the study.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: peripheral artery thrombosis (4.8%).

The registry lists serious adverse events for each dose group using the numbers at risk and the numbers affected. In the low-dose 2.5% BID group, 23 participants were at risk, 0 had a serious adverse event, 23 were at risk for other adverse events, and 2 had other adverse events. In the high-dose 5.0% BID group, 21 participants were at risk, 1 had a serious adverse event, 21 were at risk for other adverse events, and 10 had other adverse events. Deaths are listed as 0 in each group.

The registry also lists peripheral artery thrombosis as a top serious adverse event term, with 4.8%. The record does not state in the information available for this analysis which group that term belongs to or provide further context for the percentage. It should not be assigned to a dose group without that information.

These are descriptive counts from a study with the listed group sizes. In general, an adverse-event count does not by itself establish causation, and a difference between groups can be uncertain when the number of events is limited. The registry does not report a statistical comparison of adverse events, event-level details, or an assessment of relatedness. The counts should therefore be read as reported safety observations, not as a definitive estimate of comparative risk.

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

The registry record establishes that a randomized Phase I/II study evaluated low- and high-dose SF0166 Topical Ophthalmic Solution in participants with neovascular AMD. It specifies a 28-day BID treatment regimen, the primary slit-lamp outcome and its follow-up visits, and a secondary BCVA outcome. It also reports enrollment of 44 and describes the randomized analysis population as 23 participants in the low-dose group and 21 in the high-dose group.

Those details define the study question, but they do not show the primary outcome findings. The registry does not report the counts or percentages of participants with no cells at the scheduled visits, an estimated difference between doses, or an uncertainty interval. It also does not report results for the secondary BCVA outcome. Consequently, the available record cannot establish the direction, size or precision of an efficacy difference, or whether any observed comparison was statistically persuasive.

The safety counts are descriptive. The registry records 0 serious adverse events in the low-dose group and 1 in the high-dose group, with 0 deaths in each group. It also records other adverse events in both groups. These observations do not, without further information and analysis, establish whether events were caused by treatment or whether safety differs between doses.

More generally, a randomized design can strengthen comparisons between assigned groups, but interpretation still depends on complete outcome reporting, the analysis plan, missing-data handling and uncertainty estimates. The record does not report the trial's sample-size justification, analysis methods, or results for the listed efficacy outcomes. It therefore supports a description of the design and reported safety counts, not a conclusion that one regimen is superior, equivalent, or ineffective. A planning illustration, if considered, would address hypothetical design assumptions rather than observed power or the trial's own original design rationale.

13. Why This Trial Matters Statistically

This study illustrates an important distinction between a registry record's description of a trial and a report of its statistical findings. The design and outcome definitions identify what investigators intended to evaluate, but the record does not provide the primary outcome values or an analysis comparing doses. Without those results, readers cannot assess the observed effect or its precision. This is a reporting limitation, not evidence for a particular treatment effect.

The primary endpoint is collected repeatedly, from baseline through Week 8. Repeated categorical outcomes require a clear statement of the comparison being made: an individual visit, a pattern over visits, or another prespecified summary. In general, different choices can answer different questions. The registry does not explain which approach was used, making the endpoint definition alone insufficient to reconstruct the intended statistical contrast.

The record also demonstrates why analysis populations and follow-up completeness matter. It identifies all randomized participants as the primary population and notes high-dose discontinuations before scheduled visits, but does not give visit-specific denominators or missing-data methods. Those details affect how repeated results should be interpreted.

Finally, the masking description differs between the official title and the design field. That discrepancy, alongside the absence of listed outcome analyses, limits the detail available for evaluating the study's statistical conduct. The record remains useful for identifying the design, doses, outcome schedule and descriptive safety counts, while leaving key questions about analysis and efficacy results unanswered.

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 main limitation for statistical interpretation is that the registry record does not report the primary endpoint results or any outcome analyses. No visit-specific counts or percentages, dose-group contrast, uncertainty interval, or p-value is available for the primary question. The secondary BCVA outcome is named, but its results are also not reported in the information available for this analysis.

The primary outcome has multiple assessment times, yet the record does not specify which visit or summary was intended as the principal comparison. It does not describe the statistical model, the handling of repeated observations, or any multiplicity approach despite listing 17 outcome measures. These omissions prevent reconstruction of the analysis and make it impossible to distinguish planned confirmatory work from exploratory comparisons.

The primary population is described as all randomized participants, and the record notes two high-dose discontinuations at different points in follow-up. It does not report visit-level denominators, reasons for discontinuation, missing-data methods, or sensitivity analyses. Thus, the extent and treatment of missing outcome data cannot be assessed.

The record also gives inconsistent masking descriptions: the official title says double-masked, while the design field says quadruple. It does not explain the difference. The comparator information lists two active doses and does not report a placebo group. Finally, the registry does not report a sample-size justification or detailed statistical plan. These limitations restrict interpretation to the recorded design and descriptive safety information; they do not establish what the unreported results would show.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Exploratory Efficacy Study of SF0166 in the Treatment of Neovascular Age-Related Macular Degeneration (AMD) — NCT02914639.
• Registry record last updated 2023-06-07; status last verified 2023-05.
• Results first posted 2023-06-07.
• 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

NCT02914639 is a completed randomized Phase I/II parallel-group study sponsored by OcuTerra Therapeutics, Inc. It evaluated SF0166 Topical Ophthalmic Solution in neovascular AMD. The registry lists 44 participants enrolled and two active regimens: low dose 2.5% BID and high dose 5.0% BID, each instilled in the study eye for 28 days.

The primary outcome counts participants with no cells observed following slit-lamp examination from baseline through Week 8. The secondary outcome is change in BCVA from Day 0 at Week 4 and Week 8. The registry describes the primary population as 23 low-dose and 21 high-dose participants, and notes two high-dose discontinuations during follow-up.

Serious adverse events are listed for both groups, with 0 in the low-dose group and 1 in the high-dose group; deaths are listed as 0 in each group. The primary outcome values, secondary outcome results, analysis methods and statistical comparisons are not reported in the registry record.