A Multi-Center, Open Label, Extension Study Assessing the Efficacy and Safety of Additional Intravitreal Injections of RBM-007 in Subjects With Wet Age-related Macular Degeneration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Multi-Center, Open Label, Extension Study Assessing the Efficacy and Safety of Additional Intravitreal Injections of RBM-007 in Subjects With Wet Age-related Macular Degeneration (NCT04640272), a na phase 2 study. The primary outcome is Visual Acuity - Continuous.

2. Clinical Question

The study asks a follow-up question about visual acuity and safety during an extension in which participants received additional intravitreal RBM-007. Its primary outcome is a continuous measure: change in Best Corrected Visual Acuity, recorded in letters seen on an eye chart. The stated timeframe is Month 4.

Because this is a single-group, open-label study, the central question is descriptive: what changes and adverse events were recorded among the participants in the study? Without a concurrent control group, the design cannot distinguish changes associated with RBM-007 from changes that might occur for other reasons, including the course of the condition, prior treatment, or measurement variation. The registry record does not report numerical primary-outcome results, so the size and precision of any visual-acuity change cannot be assessed from the posted information.

3. Trial Design

This is a Phase 2, multi-center, open-label extension study of RBM-007 in subjects with wet age-related macular degeneration. The registry identifies the condition as exudative age-related macular degeneration and describes the study as an extension of NCT04200248. The listed intervention is RBM-007 injectable solution, administered by intravitreal injection. The registry lists enrollment as 40 and the study status as completed.

The design is single-group, with allocation listed as not applicable and masking listed as none. Consequently, participants are not assigned between a study treatment arm and a concurrent control arm in this record. The study can describe outcomes observed during treatment, but it is not structured to provide a like-for-like comparison against an untreated, placebo, or active-control group. Open-label conduct also means the registry does not describe masking of participants or study personnel.

The recorded start date is 2020-11-03 and the primary completion date is 2021-11-19. These dates describe the study record; they do not supply details about individual participant follow-up or the timing of each injection. The registry does not report the dose, injection frequency, eligibility criteria, prior-treatment requirements, or the detailed visit schedule.

The record identifies one primary outcome, Visual Acuity - Continuous, with change in Best Corrected Visual Acuity from baseline at Month 4 as its measure. It also lists secondary outcomes for categorical visual acuity and change from baseline in central macular subfield thickness. Numerical results for the primary endpoint are not reported in the registry record, and the record lists no analyses.

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:

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 Visual Acuity - Continuous, measured over Month 4.

The primary endpoint is the mean change from baseline in Best Corrected Visual Acuity at Month 4. Visual acuity is represented as letters seen on an eye chart, and the registry describes the endpoint as continuous. A continuous measure preserves the amount of change rather than reducing it to categories such as improved, unchanged, or worsened.

In general, measuring change from baseline gives a way to describe how an outcome at follow-up differs from its starting measurement. Reporting the mean describes the average change across the analyzed participants. The standard deviation, specified as the measure of dispersion, describes how spread out participant-level values are around that mean; it does not show the precision of the estimated mean in the same way that a confidence interval would.

Visual acuity is used in this trial as an outcome of interest for wet age-related macular degeneration. The endpoint as registered can describe the observed visual-acuity change in the study group, but the registry record does not give the mean, standard deviation, confidence interval, or participant count analyzed for this endpoint. Without those results, the direction, magnitude, and precision of the measured change cannot be evaluated from the posted results. The endpoint definition also does not by itself establish that an observed change was caused by the intervention.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary outcome and a single-group design. It does not report a detailed statistical analysis plan, numerical primary outcome results, or analyses. The explanations below describe general statistical concepts relevant to interpreting the registered endpoint; they do not assert that a particular method was used in this study.

What does a mean change describe?

In general, a mean change is the average of participant-level differences between a follow-up measurement and baseline. It can describe the direction and average amount of change in the analyzed group. The registry's endpoint is mean change in Best Corrected Visual Acuity from baseline at Month 4. However, it does not report the numerical estimate. The endpoint description alone therefore cannot tell readers whether the group mean increased, decreased, or remained close to baseline.

A mean can conceal variation among participants. Some individual measurements may change more than the average, while others may change less or in a different direction. The standard deviation, which the registry names as the dispersion measure, describes the spread of participant values. It is not a measure of uncertainty around the mean. A confidence interval is a general way to express uncertainty around an estimated quantity: it indicates a range of values reasonably compatible with the data and the assumptions of the analysis. No confidence interval is reported for the primary outcome.

Why does the study design matter?

In general, randomization and a concurrent comparator help distinguish differences related to the assigned interventions from differences that could arise because groups differ in other ways. This study is registered as single-group, with allocation not applicable and no masking. It therefore does not provide a concurrent control-group contrast. An observed before-and-after change, if reported, would be a description of change in the study group, not a randomized estimate of the difference between treatment strategies.

Open-label conduct is also relevant when outcomes or decisions may be influenced by knowledge of treatment. The registry lists no masking. The registry entries do not specify how visual-acuity measurements were conducted, whether assessors were masked in any way, or how decisions about treatment and follow-up were handled. Those procedural details are not reported in the registry record.

What can a significance test establish?

In general, a p-value summarizes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions were correct. It does not give the probability that a treatment works, nor does it describe the size or clinical importance of an effect. A p-value is most useful when considered alongside an effect estimate and its uncertainty. The registry record reports no analysis for the primary outcome and no primary-outcome p-value, so there is no test result to interpret.

Statistical significance and precision are distinct. An estimate may be imprecise even if a test crosses a conventional threshold, and a result that does not cross such a threshold does not prove that there is no effect. Here, without an estimate or an interval, the precision of the Month 4 mean change cannot be assessed at all. The record also does not report a pre-specified testing procedure or a statistical plan that would show how any test was selected.

How should planning calculations be understood?

General sample-size calculations ask how much information a planned study might need under specified assumptions. The registry's planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions describe a planning calculation, not the registered single-group study design. The illustration is not the trial's own design justification, and a planning sample size is not an observed power calculation.

An effect-based planning illustration depends on an observed effect estimate. Since the primary endpoint estimate is not reported in the registry record, the underlying observed effect cannot be assessed from the posted information. Any planning values should therefore be read only as hypothetical illustrations under their stated assumptions, not as evidence that the study was designed to detect a particular treatment effect or that it had a particular probability of finding one.

In general, over-dispersion means that data vary more than a statistical model assumes. When that occurs, a model that ignores the extra variation may understate uncertainty and make results appear more precise than they are. This concept is relevant only if the analysis uses a model with a variance assumption that could be violated. The registry record does not report a model for the primary endpoint, so no claim can be made about whether over-dispersion was assessed or relevant to the actual analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("RBM-007 Injectable Solution")
n   <- c(22)
m   <- c(-5.5)
sp  <- c(1.2)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  RBM-007 Injectable Solution  22  -5.500  1.200  -6.032  -4.968

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary visual-acuity outcome and secondary outcomes for categorical visual acuity and change from baseline in central macular subfield thickness. Testing multiple outcomes can raise a general multiplicity concern: when several hypotheses are tested, the chance of at least one apparently notable result can increase if each is assessed separately. In general, a protocol may address this through a pre-specified hierarchy, adjustment, or another testing strategy. The registry record does not report a multiplicity procedure, a testing hierarchy, or a detailed analysis plan. It also reports no analyses, so there are no posted outcome tests to interpret.

Missing data can affect a change-from-baseline analysis if participants lack a baseline or follow-up measurement. In general, results may depend on how missing observations are handled and on the assumptions used about why data are missing. The record does not report missing-data counts, reasons for missingness, imputation methods, or sensitivity analyses. It also does not give the participant count analyzed at Month 4; the listed enrollment of 40 does not establish how many contributed to the primary endpoint analysis.

Analysis populations matter because different rules for including participants can produce different estimates. For example, a protocol might define a population based on enrollment, treatment received, or availability of outcome measurements. Those are general possibilities, not claims about this study. The registry record does not report an intention-to-treat population, a per-protocol population, a safety population, or other analysis-population definitions. As a result, the basis for any endpoint or safety denominator cannot be fully reconstructed from the record alone.

These omissions limit reproducibility and interpretation. They do not show that the study lacked internal procedures; they mean those procedures are not reported in the registry record.

12. 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: covid-19 (4.5%).

The registry lists safety information for the RBM-007 injectable solution group. Serious adverse events were reported for 1 of 22 at risk, other adverse events for 2 of 22 at risk, and deaths for 0. The top serious term listed is COVID-19 at 4.5%. These are descriptive entries; they should not be read as comparative risks against a control group, because the study has no separate comparator arm.

In general, an adverse event is an event recorded during a study, and its occurrence does not by itself establish that the intervention caused it. A serious adverse event is a classification based on seriousness criteria; seriousness is distinct from how severe a symptom may feel. The record's safety entries do not provide enough detail to determine the nature, timing, outcome, or investigator-assessed relationship to RBM-007 for each event. The COVID-19 term and percentage should likewise be treated as a registry listing, not as proof of causation.

The safety denominator is stated as 22 at risk for both serious and other adverse events, while enrollment is listed as 40. The record does not explain the difference between these figures or provide a detailed account of the safety analysis population. These data should therefore be interpreted as the recorded safety summary, not as a complete account of every participant's experience.

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

The registry record identifies a completed Phase 2, open-label, single-group extension study of additional intravitreal RBM-007 injections for wet age-related macular degeneration. It specifies a primary outcome of mean change from baseline in Best Corrected Visual Acuity at Month 4 and lists safety outcomes. That information describes what the study set out to assess and the design used to do so.

It does not establish what happened to the primary endpoint: no numerical mean change, standard deviation, confidence interval, or primary analysis is reported in the registry record. Consequently, the posted results do not show the size, direction, or precision of any Month 4 visual-acuity change. The record's completion status does not substitute for numerical outcome reporting.

Even if a within-group change were available, the single-group design would not provide a randomized comparison. Changes observed over time may have multiple explanations, and the design does not isolate the contribution of RBM-007 from those alternatives. The open-label design and unreported analysis details also leave questions about measurement procedures, missing data, and the population used for the outcome analysis.

The safety summary reports events among participants at risk, including one serious adverse event, two other adverse events, and zero deaths in the listed group. Such counts describe recorded events; without a comparator and further event details, they do not determine comparative safety or causation.

Thus, the record supports a description of the trial's purpose, structure, registered outcome, and limited safety summary. It does not support a conclusion about the magnitude or causal effect of RBM-007 on visual acuity. The missing endpoint estimate and analysis information are central limits on what can be inferred from the posted record.

14. Why This Trial Matters Statistically

This study is statistically notable because it illustrates the distinction between defining an outcome and reporting its result. The registry specifies a continuous primary endpoint, its unit, dispersion measure, and timeframe: mean change in Best Corrected Visual Acuity from baseline at Month 4, in letters seen on an eye chart, with standard deviation. Yet the numerical estimate and analysis are not reported. A clear endpoint definition does not, on its own, allow readers to evaluate the result.

The extension design also makes the role of a comparator important. A single-group study can describe observations during follow-up, but it cannot make the same kind of direct between-group comparison as a randomized controlled study. This distinction is especially important when interpreting changes from baseline: the within-group change is not automatically an estimate of what would have happened without the intervention.

The record also separates enrollment from the analysis population. Enrollment is listed as 40, while the safety summaries use 22 at risk and the Month 4 analysis count is not reported. These figures answer different questions and cannot be treated as interchangeable. Clear reporting of participant flow, denominators, missingness, and analysis populations would help readers understand which data support each result.

Finally, effect-based planning illustrations have a different purpose from observed trial findings. Their assumptions should be kept distinct from the study's actual single-group design and from any estimate of treatment effect. The record is a useful example of why interpretation depends not only on study labels and planned measures, but also on results, uncertainty, and transparent analysis details.

15. 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 most direct limitation for interpreting efficacy is that the registry record does not report a numerical result for the primary visual-acuity endpoint. The record specifies the Month 4 mean change and standard deviation but provides no estimate, interval, p-value, or analysis count. The listed three outcome measures and zero analyses reinforce that numerical outcome analyses are not available in the record.

The study is open-label and single-group, with no concurrent comparator. This restricts interpretation to description of the study group and prevents a randomized between-group estimate. The record does not report details about the prior study's role in selecting participants, eligibility requirements, the RBM-007 dose, the injection schedule, or the visit schedule. Those details could matter when interpreting who was studied and what exposure occurred, but they are not reported in the registry record.

The registry lists enrollment as 40 but gives safety denominators of 22 at risk and does not state how many participants contributed to the Month 4 primary outcome. Participant flow and reasons for any missing measurements are not reported. Neither the approach to missing data nor the analysis populations are specified. The record also does not report confidence intervals, a statistical analysis plan, multiplicity handling, or details of endpoint measurement procedures.

Safety interpretation is limited by the brief summary of event counts and the absence of further event-level information or a comparison group. The listed counts and COVID-19 term do not establish causality or comparative risk. These limitations concern what can be determined from the registry record; they should not be taken as evidence that unreported procedures or analyses were not conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Multi-Center, Open Label, Extension Study Assessing the Efficacy and Safety of Additional Intravitreal Injections of RBM-007 in Subjects With Wet Age-related Macular Degeneration — NCT04640272.
• Registry record last updated 2023-06-08; status last verified 2023-05.
• Results first posted 2023-06-08.
• 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.

19. Record Summary

NCT04640272 is a completed Phase 2, multi-center, open-label, single-group extension study of additional intravitreal RBM-007 injections in wet age-related macular degeneration. The registry describes it as an extension of NCT04200248, lists enrollment as 40, and records a start date of 2020-11-03 and a primary completion date of 2021-11-19.

The primary outcome is mean change from baseline in Best Corrected Visual Acuity at Month 4, measured in letters seen on an eye chart, with standard deviation as the dispersion measure. Secondary outcomes include categorical visual acuity and change from baseline in central macular subfield thickness. Numerical outcome analyses are not reported in the registry record.

The safety summary lists 1 serious adverse event and 2 other adverse events among 22 at risk, with 0 deaths; COVID-19 is listed at 4.5% among the top serious terms. The study has no concurrent comparator, and the record does not report the primary endpoint estimate, its precision, or detailed analysis methods.