This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Phase I/II Trial for Intravitreous Treatment of Severe Ocular Von Hippel-Lindau Disease Using a Combination of the PDGF Antagonist E10030 and the VEGF Antagonist Ranibizumab (NCT02859441), a na phase 1, phase 2 study. The primary outcome is Tabulation of Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02859441 |
| Phase | Phase 1, Phase 2 |
| Condition | Von Hippel-Lindau Syndrome |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Eye Institute (NEI) |
| Results posted | Yes |
2. Clinical Question
Population
The trial enrolled participants with severe ocular Von Hippel-Lindau disease. The registry describes retinal capillary hemangiomas as a common and often early manifestation of the disease, with the potential for significant vision loss. The enrollment was 3. More detailed eligibility criteria and participant characteristics are not reported in the registry record.
Intervention
The intervention combined intravitreal E10030, a PDGF-B antagonist, with intravitreal ranibizumab, a VEGF-A antagonist. The study description says participants received the combination in one eye and were followed for 104 weeks. The primary outcome was a tabulation of adverse events from baseline to Week 52. The registry’s stated objective was to investigate safety and possible efficacy.
Comparator
There was no control group. The registry identifies the design as single-group and allocation as NA. Consequently, the study does not make a like-for-like comparison with another treatment or with an untreated group. The fellow eye is not described as a comparator in the registry record.
Primary question
The primary question was how many adverse events were reported through Week 52 among participants receiving the combination. The registry defines the primary measure as the total number of adverse events over that timeframe. The total result for this primary measure is not reported in the registry record. Safety information does list the number of participants affected by serious and other adverse events, but those participant counts are not the same as the total number of events.
Secondary questions concerned retinal capillary hemangioma size, ablative treatment or ocular surgery, successful ablation, and visual acuity. The registry lists 20 outcome measures, but results for these secondary measures are not reported in the registry record. The central interpretive issue is therefore not a comparison of treatment effects: it is what can be learned from the available safety counts in a small, uncontrolled study, and what remains unreported.
3. Trial Design
This was a Phase I/II, completed, single-group clinical trial sponsored by the National Eye Institute. The registry lists an enrollment of 3 and describes treatment with intravitreal E10030 and ranibizumab in one eye, with follow-up for 104 weeks. The trial’s objective was to investigate the safety and possible efficacy of the combination in severe ocular Von Hippel-Lindau disease.
Because the design is single-group and allocation is listed as NA, there is no randomized comparator. The registry also lists masking as none. The study therefore cannot estimate a comparative treatment effect against a concurrently assigned control group. Changes observed during follow-up could reflect the intervention, the underlying condition, other care, measurement variation, or a combination of influences. The record does not provide a design feature that separates these explanations.
The primary outcome was the total number of adverse events from baseline to Week 52. The study description says participants would be followed for 104 weeks, so the primary safety window covers only part of the stated follow-up. The registry record does not report the total primary-outcome count. It does provide counts of participants affected by serious and other adverse events, along with selected serious-event terms.
Secondary outcomes include measures of retinal capillary hemangioma size in the absence of other ablative treatment, ablative treatment or ocular surgery, successful ablative treatment, and mean change in visual acuity. Some outcome descriptions appear more than once in the registry listing. Results for these measures, details of the analysis population, and a statistical analysis plan are not reported in the registry record. The record lists 0 analyses.
The registry gives a start date of 2017-01-23, a primary completion date of 2019-07-09, and a completed status. These dates describe the registered study timeline; they do not supply the missing outcome results or explain how the trial was conducted beyond the design details recorded.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | E10030 and Ranibizumab |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | E10030 and Ranibizumab |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 44.7 (35 to 53) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Tabulation of Adverse Events, measured over From Baseline to Week 52.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the total number of adverse events reported from baseline to Week 52. An adverse-event count is a safety measure: it records events during a defined observation period rather than measuring a change in vision or retinal lesion size. The registry describes the outcome as a tabulation and gives its unit as adverse events.
Counting events can capture repeated events experienced by the same participant, so an event total and the number of participants who experienced at least one event answer different questions. The registry’s safety information includes counts of participants affected by serious and other adverse events. Those counts do not, by themselves, provide the total number of events required by the primary outcome definition. The total primary-outcome count is not reported in the registry record.
Safety monitoring is appropriate to the stated Phase I/II objective of investigating a combination of investigational treatments. A defined timeframe makes the intended observation window explicit, while a tabulation can describe the kinds and frequency of events recorded. However, the endpoint alone does not establish whether an event was caused by treatment, how severe every event was, or whether the observed safety experience would be similar in a larger or different population. Those interpretations require more detail than the registry reports.
The registry names adverse events through Week 52 as the primary outcome and lists other outcomes concerning lesion size, procedures, and visual acuity. The endpoint definition does not replace those other measures, and the registry record does not report their results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The available results support a narrow descriptive reading. The registry lists 3 participants at risk for serious adverse events, with 2 affected, and 3 at risk for other adverse events, with 3 affected. It lists 0 deaths. The serious-event terms shown are nephrolithiasis and dehydration, each reported as 33.3%. These figures describe the recorded safety experience in this study; they are not a comparison with another group.
The primary outcome was defined as the total number of adverse events through Week 52, but that total is not reported in the registry record. Counts of participants affected cannot be substituted for a total event count: a participant can experience more than one event, and a participant-level count does not convey how many events occurred. The registry’s selected serious-event terms also do not constitute a complete account of every event or its timing.
There is no randomized control group, and masking is listed as none. As a result, the observed counts cannot establish whether an event was more or less common because of the treatment. They also cannot distinguish treatment effects from the course of the disease, other care, or chance variation. The trial’s enrollment of 3 makes the reported experience especially limited as a basis for describing safety beyond the participants studied.
The study was intended to investigate possible efficacy as well as safety, but the registry lists no results for the secondary outcomes concerning retinal capillary hemangioma size, ablative procedures, surgery, or visual acuity. Their outcome definitions should not be mistaken for observed findings. The record lists 20 outcome measures and 0 analyses; it does not report estimates, uncertainty intervals, or statistical tests for these outcomes.
Accordingly, the registry supports reporting the recorded safety counts and the study’s design, while leaving important questions unanswered. It does not provide the primary adverse-event total, detailed outcome results, or a controlled estimate of treatment effect. No conclusion about comparative efficacy or comparative safety follows from these data alone.
9. Statistical Methods Explained
The registry describes a single-group study with allocation listed as NA and masking listed as none. These design features determine what kinds of statistical conclusions are available. A single-group study can describe what was observed among people who received the intervention. Without a comparison group, it cannot directly estimate how outcomes would have differed under another treatment or no treatment. Lack of masking can also matter when outcomes involve judgment or measurement, although the registry does not report how outcome assessors were managed.
What does an event count represent?
For a count outcome, the basic observation is the number of events recorded during the specified period. That is distinct from the number of participants who experienced an event. If an individual experiences multiple events, the event total can include each event, whereas a participant count records that individual as affected. The registry defines the primary outcome as the total number of adverse events from baseline to Week 52, but that total is not reported in the registry record. The available affected-participant counts therefore answer a related, but different, question.
Statistical models for counts may need to account for how variable the counts are across participants. As a general statistical matter, a simple count model can be unsuitable when the observed variation is greater than the model expects; this is called over-dispersion. Model choice can affect estimated uncertainty and resulting intervals or tests. The registry record does not report a model, the distribution of individual event counts, or a statistical analysis plan, so it is not possible to assess whether or how over-dispersion was considered.
How should uncertainty be understood?
A confidence interval is a statistical summary of uncertainty around an estimate under the assumptions of the method used. In general, an interval gives readers more information about precision than a point estimate alone. It does not correct for an uncontrolled design, missing outcome reporting, or limitations in how participants were selected. The registry does not report confidence intervals for the outcomes. No interval can therefore be interpreted as a reported study result.
With enrollment of 3, the descriptive counts reflect a very small study. General statistical reasoning cautions that results from a small group can be sensitive to the experience of each participant. This makes precise estimates difficult, but it does not justify calculating a new estimate from the registry’s summaries. The record does not provide the full event data needed to evaluate event patterns, repeated events, or participant-level variation.
What can a one-group design estimate?
A one-group design can report the outcomes observed during follow-up and can help describe what was recorded in that group. It does not supply the counterfactual outcome: what would have happened to those same participants under a different condition. A comparison with historical expectations would require an appropriate external source and a defensible method; such a comparison is not reported in the registry record. The listed safety counts should therefore be read descriptively, not as a treatment-attributable risk estimate.
The absence of masking is another design consideration. When the people delivering care or assessing outcomes know the intervention, assessment or reporting may be influenced in some settings. This is a general methodological concern, not evidence that bias occurred in this trial. The registry does not report whether independent assessment or other safeguards were used.
How do planning calculations differ from study results?
Sample-size calculations are planning illustrations, not observed power. A planning calculation depends on assumptions about the effect to detect, the significance level, allocation, and statistical method. The registry record does not report the trial’s own sample-size justification or a statistical plan. Any planning illustration associated with a posted effect would not change the enrollment or establish what the study was capable of detecting after completion. No numerical planning result is reported in the registry entries for interpretation.
More generally, observed power calculated after a study is not a substitute for an estimate and its uncertainty. Interpretation should focus on the observed outcome and its precision, along with the design’s limitations. Here, the primary event total and the secondary outcome results are not reported in the registry record, so those quantities cannot be assessed from the available information.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures, including safety, retinal capillary hemangioma size, ablative treatment or ocular surgery, successful ablation, and visual acuity. Some secondary outcome descriptions appear more than once. A list of outcome measures is not the same as a report of results, and the registry record does not report results for these secondary measures.
When a study examines many outcomes or performs repeated statistical tests, the chance of obtaining at least one apparently notable result by chance can increase. Statistical approaches can address this issue, for example by specifying a primary outcome, a testing hierarchy, or an adjustment for multiple comparisons. This is general statistical context. The registry record does not report whether any multiplicity strategy was planned or applied. It lists 0 analyses, so no reported tests or adjusted results are available to evaluate.
The record identifies the primary safety outcome and its timeframe, but the total event count is not reported. It does not describe an analysis population, exclusions from analysis, or how participants with incomplete follow-up were handled. The missing-data policy is not reported in the registry record. It is therefore not possible to tell whether any outcome data were missing, how missing observations were treated, or whether the analysis included everyone enrolled.
These gaps matter because analysis choices can influence estimates and their uncertainty, particularly when the study is small or several outcomes are considered. They do not prove that data were missing or that multiplicity changed any result; those details are simply not reported in the registry record. The registered outcome definitions should not be read as confirmation that all outcomes were measured, analyzed, or fully reported.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| E10030 and Ranibizumab | 2 | 3 | 66.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| E10030 and Ranibizumab | 0 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| E10030 and Ranibizumab | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | E10030 and Ranibizumab |
|---|---|---|
| Nephrolithiasis | Renal and urinary disorders | 1 of 3 |
| Dehydration | Metabolism and nutrition disorders | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | E10030 and Ranibizumab |
|---|---|---|
| Visual Acuity Reduced | Eye disorders | 2 of 3 |
| Ocular Hypertension | Eye disorders | 1 of 3 |
| Back Pain | Musculoskeletal and connective tissue disorders | 1 of 3 |
| Hypoaesthesia | Nervous system disorders | 1 of 3 |
| Infection | Infections and infestations | 1 of 3 |
| Posterior Capsule Opacification | Eye disorders | 1 of 3 |
| Vomiting | Gastrointestinal disorders | 1 of 3 |
| Weight Decreased | Investigations | 1 of 3 |
| Eye Pain | Eye disorders | 1 of 3 |
| Limb Injury | Injury, poisoning and procedural complications | 1 of 3 |
Serious events with the highest arm-level rate: nephrolithiasis (33.3%), dehydration (33.3%).
The registry lists 3 participants at risk for serious adverse events and 2 participants affected. For other adverse events, it lists 3 at risk and 3 affected. It reports 0 deaths. The top serious-event terms are nephrolithiasis at 33.3% and dehydration at 33.3%.
These are descriptive safety figures from a single-group study, not comparisons with a control group. Affected-participant counts indicate how many participants were recorded as having an event in the relevant category; they do not state the total number of events. A participant could have more than one event, and the registry does not provide enough detail to determine whether the listed serious-event terms occurred in the same or different participants. The percentages attached to the terms should be read as reported, not used to infer additional counts or patterns.
The primary outcome was the total number of adverse events through Week 52, but that total is not reported in the registry record. The available safety summary therefore does not fully answer the primary endpoint question. Nor does it establish that the intervention caused the events or that the observed experience would apply to other participants. The small enrollment and absence of a control group limit broader interpretation.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed Phase I/II single-group trial evaluated intravitreal E10030 plus ranibizumab in severe ocular Von Hippel-Lindau disease. The study description specifies treatment in one eye and follow-up for 104 weeks. The primary safety outcome was defined as the total number of adverse events from baseline to Week 52. The safety summary reports affected-participant counts for serious and other adverse events, selected serious-event terms, and 0 deaths.
Those details describe what the registry records, but they do not provide the total primary adverse-event count. They also do not provide results for the listed measures of retinal capillary hemangioma size, procedures, surgery, or visual acuity. The registry’s stated interest in possible efficacy is an objective, not an efficacy finding. Outcome definitions and a completed status do not show that a treatment benefit was observed.
The single-group design has no concurrent control, so the findings cannot establish what would have happened under another treatment or without the intervention. The lack of masking is another design feature to consider, but the registry does not describe its effect on outcome assessment. With enrollment of 3, the observed safety experience is limited to a very small group and does not by itself characterize experience in a broader population.
The record also does not report a statistical analysis plan, confidence intervals, analyses, or a missing-data approach. These omissions limit assessment of the precision and completeness of the results. The study can be understood as a small descriptive investigation with recorded safety information, but the registry results do not support a comparative estimate of efficacy or safety.
In short, the posted information documents the study’s design and selected safety counts. It does not report the primary event total or the secondary outcome findings needed to answer the broader questions posed by the trial.
13. Why This Trial Matters Statistically
This trial is statistically informative in part because it illustrates the distinction between an outcome’s definition and its reported result. The primary outcome is clearly described as a total adverse-event count over a specified period, yet that total is not reported in the registry record. The registry does provide affected-participant counts, which are useful safety descriptions but do not substitute for the event total.
The single-group design also shapes interpretation. Without a control group, the study can describe what was recorded among treated participants but cannot make a like-for-like estimate of how outcomes compare with another treatment or no treatment. This remains true even when a study has a stated objective to investigate possible efficacy. The objective does not itself establish a comparative result.
Enrollment of 3 emphasizes why precision and completeness matter. In a small study, participant-level counts can be strongly influenced by the experience of each person. Reporting event totals, outcome estimates, and uncertainty would help readers understand the observed data, but the registry does not report the primary event total or secondary results. The registry lists 20 outcome measures and 0 analyses, so the available record does not show how those outcomes were analyzed or how multiple outcomes were handled.
The trial’s safety summaries still have descriptive value: they record the number of participants affected by serious and other adverse events, selected serious-event terms, and deaths. Their statistical meaning is limited to this study’s recorded experience. They should not be treated as comparative risks or evidence of cause. This distinction between description, precision, and causal comparison is central to reading small early-phase studies responsibly.
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.
Several limitations are specific to this trial record. Enrollment was 3, and the study was single-group, with allocation listed as NA and masking listed as none. There is no concurrent control for interpreting the safety counts or the intended efficacy outcomes. The record does not report a statistical analysis plan or an analysis population.
The primary outcome was the total number of adverse events through Week 52, but the total is not reported in the registry record. The safety information instead gives participant counts for serious and other adverse events and selected serious-event terms. These summaries do not provide event timing, duration, recurrence, or a complete event-level account in the registry record recorded. The registry does not report the secondary outcome results concerning lesion size, ablative treatment, ocular surgery, or visual acuity.
The stated follow-up was 104 weeks, while the primary safety outcome timeframe ends at Week 52. The registry does not report how outcomes after the primary safety window were summarized, or whether follow-up was complete for every participant. Missing-data handling and reasons for any incomplete observations are not reported in the registry record.
The registry lists 20 outcome measures, with some secondary descriptions repeated, and 0 analyses. It does not report a multiplicity approach, confidence intervals, or statistical tests. These omissions prevent assessment of precision, analytic choices, and the completeness of outcome reporting. They should be treated as reporting limitations, not as proof that particular methods were or were not used.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase I/II Trial for Intravitreous Treatment of Severe Ocular Von Hippel-Lindau Disease Using a Combination of the PDGF Antagonist E10030 and the VEGF Antagonist Ranibizumab — NCT02859441.
- Registry record last updated 2021-11-01; status last verified 2019-07.
- Results first posted 2020-07-14.
- 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.
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18. Record Summary
NCT02859441 is a completed Phase I/II, single-group trial sponsored by the National Eye Institute. It enrolled 3 participants with severe ocular Von Hippel-Lindau disease to receive intravitreal E10030 and ranibizumab, with the study description specifying treatment in one eye and follow-up for 104 weeks.
The primary outcome was the total number of adverse events from baseline to Week 52. That total is not reported in the registry record. Safety information lists 2 of 3 participants affected by serious adverse events, 3 of 3 affected by other adverse events, and 0 deaths; nephrolithiasis and dehydration are each listed at 33.3% among the top serious-event terms.
The registry lists 20 outcome measures and 0 analyses. Results for secondary outcomes, the statistical analysis plan, and missing-data methods are not reported in the registry record. The uncontrolled design supports descriptive interpretation only.