Pilot Study of X-82 in Patients With Wet AMD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study of X-82 in Patients With Wet AMD (NCT01674569), a non-randomized phase 1, phase 2 study. The primary outcome is Change From Baseline Visual Acuity at 6 Months.

2. Clinical Question

This study addressed whether different oral X-82 dose schedules, given alongside intravitreous ranibizumab, could be evaluated for safety and preliminary biologic activity or efficacy in people with wet age-related macular degeneration. The primary measure was change in best-corrected visual acuity at 6 months. The registry describes the study as a dose-escalation trial and identifies visual acuity, fluorescein leakage, retinal thickness and fibrosis as areas of preliminary efficacy assessment. Only the visual-acuity measure is identified as the primary endpoint.

These details frame the question as an evaluation of dose schedules and preliminary activity, not a randomized estimate of X-82’s effect against an untreated or otherwise equivalent control group. The record does not report enough outcome information to answer how visual acuity changed.

3. Trial Design

The registry identifies this as a Phase 1 and Phase 2 study, with a dose-escalation design. It was non-randomized, open-label, and parallel. Enrollment was 35, the study is listed as completed, and its condition is exudative macular degeneration. The recorded start was 2012-10 and primary completion was 2015-02. The sponsor was Tyrogenex.

Participants were assigned to listed regimens combining oral X-82 with intravitreous ranibizumab (Lucentis). The six schedules included 50 mg or 100 mg on alternate days, and 50 mg, 100 mg, 200 mg or 300 mg once daily. Ranibizumab retreatment followed predefined criteria. The listed treatment period was 24 weeks or until unacceptable toxicity developed or occurred. The precise number of participants in each schedule is not reported in the registry record.

Non-randomized allocation means that assignment was not described as random. Open-label means masking was absent. In general, these features matter because differences among dose groups may reflect factors other than the dose schedule, and knowledge of treatment can influence some aspects of care or assessment. They do not, by themselves, establish that bias occurred; they do limit how confidently a difference between groups could be attributed to X-82 dose.

The registry record does not report the allocation procedure, the rationale for the selected schedules, or how escalation decisions were made. It also does not report a protocol-level statistical analysis plan, sample-size justification, or interim-analysis plan. The listed description of the primary endpoint says the mean and standard deviation were calculated for subjects who completed 6 months of treatment with oral X-82; it does not give group-specific results or a method for handling incomplete follow-up.

Because the schedules all included ranibizumab and allocation was non-randomized, the arms should not be read as a like-for-like control comparison. The study’s stated objective was to evaluate safety and preliminary biologic activity or efficacy. That objective and design support a descriptive reading of the posted information, but the registry record does not provide the outcome analyses needed to quantify preliminary activity.

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: 110 subjects were screened for entry into the study. 52 did not meet inclusion criteria, 19 declined to participate and 4 were excluded for other reasons

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The mean and standard deviation was calculated for all subjects who completed 6 months of treatment with oral X82

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 Change From Baseline Visual Acuity at 6 Months, measured over 6 months.

The primary endpoint was change from baseline in visual acuity at 6 months, measured in ETDRS letters. Best-corrected visual acuity was assessed at baseline and at various times during the study using the Early Treatment Diabetic Retinopathy Study method. In this method, the participant reads letters of decreasing size on a chart from a defined distance. For each subject, the change was defined as visual acuity at 6 months minus baseline visual acuity. A positive change was defined in the registry as improvement in visual acuity.

Change from baseline is used to describe how a measurement differs from its starting value. In general, this can help distinguish a follow-up measurement from the level participants had before treatment. The registry says ETDRS visual acuity was also used during the study to monitor the need for rescue therapy. The endpoint description does not report the actual mean change, its standard deviation, or results by dose schedule.

The stated analysis population was all subjects who completed 6 months of treatment with oral X-82. This is a completion-based population, not necessarily every enrolled participant. The number who completed that period and the number contributing to the endpoint are not reported in the registry record. The endpoint description also does not explain how missing six-month measurements were handled. These gaps matter because a result among completers may not describe all enrolled participants if completion or measurement availability differs across participants.

The study summary also names fluorescein leakage, retinal thickness and fibrosis as preliminary efficacy assessments, if detectable. Those measures do not replace the stated primary endpoint in the record. No numerical results for visual acuity or these other assessments are reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous endpoint: change in visual acuity measured as a number of ETDRS letters. It says the mean and standard deviation were calculated among subjects who completed 6 months of treatment with oral X-82. No numerical mean or standard deviation is reported in the registry record. The explanations below describe the statistical concepts generally; they are not claims that a particular analysis was performed in this study.

What does a mean change summarize?

In general, a mean change is the average of participants’ individual follow-up minus baseline measurements. The study’s endpoint description specifies that subtraction order: baseline visual acuity is subtracted from visual acuity at 6 months. A positive value therefore represents an increase in letters according to the registry’s definition. A mean gives a compact summary of the group, but it does not show whether all participants changed in a similar way. Participants may have changes above and below the mean.

The registry says the endpoint was calculated for subjects who completed 6 months of treatment. That statement identifies a completion-based population for the reported measure, but not the number of people included. In general, a mean based only on participants with complete follow-up may differ from a mean for everyone enrolled if participants with missing measurements have different outcomes. The record does not report missing-data handling or explain whether any alternative analysis population was used.

What does a standard deviation describe?

In general, the standard deviation describes how spread out individual measurements are around the mean. A smaller spread indicates participants’ changes were more clustered around the average; a larger spread indicates greater variation. It is not the same as the uncertainty in the estimated mean. The registry names standard deviation as the dispersion measure, but does not report its value. Readers therefore cannot assess the observed variability or use it to judge the precision of the average from this record alone.

How would a confidence interval help?

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical method. It communicates uncertainty around the estimated mean or difference, rather than only showing a single point estimate. A narrow interval indicates greater precision than a wide interval, given the method and data. No confidence interval is reported for the primary endpoint in the registry record. A confidence interval would not, by itself, remove limitations caused by non-randomized allocation, incomplete follow-up or other design features.

What do the design labels imply for comparisons?

The study is listed as non-randomized, open-label and parallel. In general, randomization helps balance measured and unmeasured participant characteristics across groups, while masking can reduce the influence of treatment knowledge on care and assessment. Here, allocation was non-randomized and masking was absent. This does not prove that a particular result is biased, but it means that an observed difference between dose schedules would need cautious interpretation. The registry record does not report an adjusted between-group analysis.

All listed schedules combine oral X-82 with intravitreous ranibizumab, with retreatment under predefined criteria. Thus, the listed groups are not described as an X-82 group against a group receiving no X-82. The registry’s own note says the arms are not a like-for-like control comparison. Without random assignment and a suitable control, differences across arms cannot automatically be attributed to the dose or schedule.

What is over-dispersion, and is it relevant?

In general, over-dispersion means that observed variability is greater than a statistical model assumes. It can make model-based uncertainty estimates too small if not accounted for. This concept is particularly relevant to some count-data models. The primary endpoint is described as a continuous mean change with standard deviation, and the registry record does not report a model or an over-dispersion assessment. It would be inappropriate to claim that over-dispersion was present or that a correction was used.

How should planning calculations be read?

The sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. Such calculations are hypothetical planning scenarios. They are not observed power, and they do not show that the trial had a given probability of finding an effect. The registry’s assumptions do not replace a protocol sample-size justification; that justification is not reported in the registry record.

The interpretation of any planning illustration depends on the effect used as its starting point and on its assumptions. The registry record does not report the numerical primary-endpoint result or a protocol-based sample-size justification. For this reason, the illustration should not be treated as an independent confirmation of the endpoint result or as evidence about what the study observed. The actual enrollment reported was 35, while the endpoint population was defined by six-month completion; the number completing is not reported.

The registry lists one outcome measure and no analyses. It does not report an analysis method for comparing schedules, adjustment for baseline values, handling of rescue therapy in the endpoint analysis, or interim analyses. These omissions mean readers cannot reconstruct a full statistical analysis from the record. General statistical concepts help explain what a result could mean, but they cannot supply analyses or estimates that are not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the change from baseline in visual acuity at 6 months, and reports no analyses. It also names visual acuity, fluorescein leakage, retinal thickness and fibrosis as areas of preliminary efficacy assessment in the study summary. The record does not specify whether these additional assessments were formal endpoints, how many comparisons were planned, or how multiplicity was handled. Multiplicity arises in general when several outcomes, time points or group comparisons are examined; without a plan, the chance of obtaining a seemingly notable result by chance can be difficult to judge. No multiplicity adjustment or hierarchy of outcomes is reported in the registry record.

The registry does not report a statistical analysis plan or an interim-analysis plan. It does not describe whether comparisons among dose schedules were prespecified, whether analyses were adjusted for baseline measurements, or how rescue therapy was incorporated into endpoint analyses. These details should not be inferred from the study’s dose-escalation label or from the endpoint description.

The stated primary-endpoint population consists of subjects who completed 6 months of treatment with oral X-82. The number of completers and the number with observed six-month visual-acuity measurements are not reported in the registry record. Reasons for missing data, withdrawals and any methods for handling missing measurements are not reported either. In general, missing-data methods matter because the analysis can depend on why measurements are unavailable and on the assumptions made about unobserved outcomes.

The record does not report an intention-to-treat population, a per-protocol population, or any other analysis population beyond the completion-based wording for the primary endpoint. It also does not report how participants who received rescue therapy were handled in the primary analysis, although visual acuity was used to monitor the need for rescue therapy. These are important limits when interpreting any result, and no numerical result is available to assess.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain (2.9%), acute renal failure (2.9%), congestive heart failure (2.9%), multiple myeloma (2.9%).

The registry reports one safety group, titled Dose Escalation of X-82 and Ranibizumab Rescue. It lists 35 participants at risk for serious adverse events and 3 affected. For other adverse events, it lists 35 at risk and 28 affected. Deaths are reported as 0. These are the recorded figures; the registry record does not provide a fuller account of event timing, severity beyond the serious-event classification, or participant-level overlap between the categories.

The record also lists Chest pain, Acute renal failure, Congestive heart failure and multiple myeloma among the top serious-event terms, each at 2.9%. These terms and percentages should be read as reported, not as evidence about cause. The registry information does not establish whether an event was judged related to X-82, ranibizumab, the underlying condition or another factor. The number of participants affected by each term is not separately stated in the registry record.

In general, adverse-event counts describe events observed and recorded during a study; they do not alone establish that a treatment caused an event. The safety figures also do not provide a randomized comparison, and the arms are explicitly not a like-for-like control comparison. They should therefore be understood as descriptive safety reporting, not as a comparative estimate of risk. The treatment period listed for the regimens was 24 weeks or until unacceptable toxicity developed or occurred.

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

The record establishes what the investigators intended to measure: change from baseline in ETDRS visual acuity at 6 months, among subjects completing 6 months of oral X-82 treatment. It also defines the direction of the measure, with positive change indicating improvement. But the record does not report the mean change, its standard deviation, an interval estimate, or a statistical test. It therefore does not show the observed visual-acuity result or how precise an estimate might be.

The design provides context but not a substitute for those missing results. This was a non-randomized, open-label, parallel dose-escalation study with 35 participants enrolled. The listed schedules combined oral X-82 and ranibizumab. Because allocation was not randomized and no like-for-like control is described, differences between schedules would not automatically identify an effect caused by dose. The registry record reports no comparative efficacy analysis.

The safety information offers descriptive counts: 3 of 35 participants at risk were affected by serious adverse events, 28 of 35 were affected by other adverse events, and deaths were 0. The record also lists four serious-event terms at 2.9% each. These figures do not establish causation, and they are not an efficacy result. The registry information does not state whether the listed events were attributed to either treatment.

In general, a study can contribute descriptive information even when it cannot provide a reliable comparative treatment effect. Here, however, the absence of the primary outcome estimate limits even a descriptive account of the visual-acuity change. The completion-based endpoint population and the unreported number of completers further limit assessment of how representative the endpoint would be of all enrolled participants.

The record supports a careful account of study design, endpoint definition and reported safety counts. It does not support a conclusion about the direction, size or precision of visual-acuity change, nor a causal comparison of X-82 schedules. Those conclusions require outcome results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

Statistically, this trial is a useful example of the distinction between a clearly defined endpoint and an interpretable result. The registry explains how the primary outcome was formed: the six-month ETDRS visual-acuity score minus baseline, summarized by a mean and standard deviation in subjects who completed 6 months of oral X-82 treatment. Yet the numerical estimate and dispersion are absent. A definition tells readers what the investigators planned to measure; it does not show what was observed.

The study also makes the role of design visible. It is a non-randomized, open-label dose-escalation study, and its listed regimens combine X-82 with ranibizumab. The record explicitly warns that the arms are not a like-for-like control comparison. In general, separating treatment effects from group differences is more difficult without random allocation and an appropriate control. This is a reason to describe observed comparisons cautiously, not a reason to invent a result or assume that bias occurred.

The completion-based primary-endpoint population illustrates another basic issue: the participants enrolled and the participants contributing to an endpoint may not be the same set. The record gives enrollment of 35, but not the number completing six months or the endpoint denominator. Missing-data methods are not reported, so readers cannot judge how incomplete follow-up might affect the outcome summary.

The sample-size section also illustrates a distinction between planning and observation. Its assumptions describe hypothetical calculations tied to the observed effect, not observed power. Such calculations are not a substitute for a protocol-based sample-size rationale or for reporting the endpoint estimate and its uncertainty. The registry does not report that rationale.

Finally, safety counts and efficacy outcomes answer different questions. Serious and other adverse-event counts provide descriptive safety information, while the primary endpoint concerns change in visual acuity. Keeping these evidence types separate helps prevent a reader from treating one as a proxy for the other. The record is informative about the study’s structure and intended measurement, but its missing outcome analysis constrains statistical interpretation.

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 central limitation for interpretation is that the registry defines the primary endpoint but does not report its numerical results. There is no mean change in ETDRS letters, standard deviation, confidence interval or test result in the record. The number of participants completing 6 months of treatment and contributing endpoint measurements is also not reported. Consequently, readers cannot assess the observed change, its variability or its precision.

The design imposes additional limits on any possible comparison. Allocation was non-randomized, masking was absent, and all listed dose schedules included ranibizumab. The registry itself notes that the arms are not a like-for-like control comparison. The number of participants in each dose schedule and the allocation procedure are not reported in the registry record. These features mean that a difference between schedules, if reported elsewhere, would require cautious interpretation.

The record does not report the protocol’s sample-size justification, statistical analysis plan, interim-analysis plan, multiplicity approach, missing-data method or the handling of rescue therapy in the endpoint analysis. It does not specify whether any adjustment for baseline values or other participant characteristics was made. These omissions prevent readers from reconstructing the intended statistical analysis or assessing whether reported analyses followed a prespecified plan.

The endpoint population is based on completing 6 months of oral X-82 treatment. The registry does not report reasons for non-completion, the number with missing visual-acuity measurements or whether completion differed by schedule. In general, these details matter when considering how well a completer-based summary represents everyone enrolled.

The safety figures are also limited in scope: the record reports affected counts and selected serious-event terms, but does not provide attribution or a randomized comparator. The listed adverse events therefore cannot establish causation. These limitations are specific to what is reported in this registry record; they should not be filled in by assuming unreported methods or results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pilot Study of X-82 in Patients With Wet AMD — NCT01674569.
• Registry record last updated 2018-08-07; status last verified 2018-07.
• Results first posted 2018-06-27.
• 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 Phase 1 and Phase 2, non-randomized, open-label, parallel dose-escalation study of oral X-82 with intravitreous ranibizumab in people with exudative macular degeneration. Enrollment was 35. The listed regimens varied in X-82 dose and schedule, with ranibizumab retreatment based on predefined criteria.

The primary endpoint was change from baseline in ETDRS visual acuity at 6 months, summarized as a mean and standard deviation among subjects who completed 6 months of oral X-82 treatment. The numerical endpoint result, endpoint denominator and analysis are not reported in the registry record. The record reports 3 participants affected by serious adverse events, 28 affected by other adverse events, and 0 deaths among 35 at risk. The design and missing outcome information limit conclusions about comparative effects.