Efficacy, Safety And Tolerability Study Of RN6G In Subjects With Geographic Atrophy Secondary to Age-related Macular Degeneration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy, Safety And Tolerability Study Of RN6G In Subjects With Geographic Atrophy Secondary to Age-related Macular Degeneration (NCT01577381), a randomized phase 2 study. The primary outcome is Mean Reduction (in Study Eye) in Rate of Growth of Geographic Atrophy (GA) at Day 309.

2. Clinical Question

In practical terms, the study was designed to assess a structural measure of retinal disease progression, alongside visual-function outcomes. The record lists secondary assessments of best corrected visual acuity, low-luminance best corrected visual acuity and contrast sensitivity at several follow-up times and at the end of the study. These planned assessments do not establish that results were obtained or analyzed. The registry lists 33 outcome measures, but reports no analyses for the primary endpoint. Consequently, the record does not answer the intended comparative efficacy question. It also does not establish a dose-response pattern: although several dose groups are listed, there is no primary endpoint estimate with which to compare them.

3. Trial Design

This was a phase 2, randomized, parallel-group, placebo-controlled study of RN6G in people with geographic atrophy secondary to age-related macular degeneration. The official title describes a multicenter, double-masked, multidose study and includes efficacy, safety, pharmacokinetics and pharmacodynamics among its aims. The registry classifies the masking as quadruple. These descriptions differ; the record does not explain the difference or specify which individuals were masked.

The recorded study start was 2012-08, and the primary completion date was 2013-09. The study status is terminated. The registry reports 10 participants enrolled. Its primary-endpoint description states that the analysis was not performed because the study ended early and there were not enough participants or data for meaningful analyses. The reason for termination is not reported in the registry record.

The active intervention is identified as RN6G and PF-04382923. The adverse-event group descriptions identify three active dose groups: 2.5 mg/kg, 7.5 mg/kg and 15.0 mg/kg. Placebo was the comparator. The registry says eight participants were assigned to active drug, with one not dosed, and notes notable variability in how many doses were received. The arm descriptions provide no additional detail on dosing schedules or treatment duration.

Randomization and masking can, in general, reduce the influence of allocation choices and expectations on comparisons. They do not guarantee that a trial will produce an interpretable efficacy estimate. In this study, the small enrollment and early termination prevented the planned primary analysis, according to the registry record. Details of the randomization method, allocation concealment, original target enrollment and sample-size justification are not reported in the registry record. Nor is there enough information to reconstruct how participants were distributed at randomization beyond the available assignment and adverse-event group counts.

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: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).

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 Mean Reduction (in Study Eye) in Rate of Growth of Geographic Atrophy (GA) at Day 309, measured over Baseline and Day 309.

The primary endpoint was the mean reduction in the rate of growth of geographic atrophy in the study eye at Day 309. The registry describes geographic atrophy as an advanced form of dry age-related macular degeneration. It says the change in geographic atrophy area was based on fundus autofluorescence at 30 days after the last dose.

This endpoint concerns the rate at which the measured atrophic area changes, rather than visual acuity itself. In general, an image-based measure of lesion area can provide a structural way to track disease progression, while visual-function measures assess a different aspect of the condition. The registry lists visual acuity, low-luminance visual acuity and contrast sensitivity among its secondary outcomes, but it reports no primary endpoint analysis to compare with those measures.

The endpoint title refers to a reduction in the rate of growth. That wording describes the intended measure, not an observed result. The record gives no estimate of the mean reduction, no uncertainty interval and no treatment comparison for the endpoint. It states that analysis was not performed because the trial ended early and the available participants and data were insufficient for meaningful analyses. The endpoint therefore cannot be used to quantify an effect of RN6G in this trial.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods matter because the intended design and the available results answer different questions. The record describes a randomized, parallel-group, placebo-controlled phase 2 study, but it also states that the primary endpoint analysis was not performed. Statistical methods can clarify what a completed analysis would ordinarily estimate; they cannot recover an effect estimate when the registry reports none.

What would a randomized comparison estimate?

In general, randomization assigns participants to study groups using a chance-based procedure. Its purpose is to reduce systematic differences between groups at the time of assignment, so that later outcome comparisons can be interpreted more fairly. A parallel-group design follows separate groups assigned to different interventions. A placebo-controlled design uses placebo as the comparison condition. The registry record does not describe the precise randomization procedure, allocation concealment or planned analysis population, so those details cannot be assessed.

For the stated primary endpoint, an analysis would need to summarize the measured change in geographic atrophy area and compare the relevant study groups according to the planned approach. The title specifies a mean reduction in the rate of growth, measured in the study eye at Day 309. The registry gives no estimate or group-level summary for this endpoint. Therefore, no recalculated comparison is possible from the recorded primary results, and no statistical significance or uncertainty can be described.

What does uncertainty mean?

In general, a confidence interval describes a range of values compatible with the data and the statistical model at a stated confidence level. A narrower interval usually indicates greater precision, while a wider interval indicates greater uncertainty. A p-value, in general, measures how unusual data at least as extreme as those observed would be under a specified null hypothesis and model. Neither quantity gives the probability that a treatment works. No confidence interval or p-value for the primary endpoint is reported in the registry record, so precision and statistical evidence for that comparison cannot be evaluated.

Why does the small enrollment matter?

With few participants, estimates can be strongly influenced by individual observations and may be imprecise. Small groups also limit the ability to describe variability, examine differences across dose levels or assess whether group characteristics were balanced. Here, the registry itself says there were not enough participants or data for meaningful primary analyses. It records 10 participants enrolled and reports that eight were assigned to active drug, including one who was not dosed. The record also notes variability in the number of doses received. These registry entries reinforce the importance of treating the safety counts as descriptive rather than as stable comparative estimates.

Sample-size planning is distinct from observed results. In general, a planning calculation uses assumptions about the target effect, variability, significance level, allocation and analysis method to estimate the enrollment needed for a future study. The registry’s stated planning framework describes 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 an observed effect. It also distinguishes total event counts for time-to-event calculations from participants per arm for other calculations. Such planning illustrations are not observed power, do not represent the trial’s original design unless documented as such, and cannot substitute for an outcome analysis. The trial’s original sample-size justification is not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion occurs when the observed variability in data is greater than a statistical model assumes. If a model understates variability, standard errors may be too small and confidence intervals too narrow. A small trial can make variability difficult to estimate reliably. The registry record does not report a model for the primary endpoint, a dispersion estimate or an over-dispersion assessment. It would therefore be inappropriate to assert that any particular model was used or that over-dispersion was present.

What can be inferred from the listed outcomes?

The registry lists 33 outcome measures, including visual-function and contrast-sensitivity measures at follow-up times and at the end of the study. In general, analyzing many outcomes or time points can raise multiplicity concerns: the more comparisons considered, the greater the chance of finding an apparently notable result by chance if no adjustment or prespecified hierarchy is used. The record does not report a multiplicity procedure or the planned hierarchy of outcomes. It also reports zero analyses. Accordingly, there are no posted outcome comparisons from which to assess multiplicity-adjusted or unadjusted evidence.

Missing-data methods are also important in a terminated study. In general, an analysis plan should explain how unavailable measurements are handled and whether the primary analysis includes all randomized participants, only participants who received treatment, or another defined group. The registry does not report the missing-data approach or analysis populations. Because the primary analysis was not performed, the record cannot show how incomplete follow-up or dosing variation would have been handled.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 33 outcome measures, including the primary geographic atrophy measure and secondary visual-function and contrast-sensitivity outcomes. Considering multiple outcomes and time points can increase the chance of a seemingly notable finding when many comparisons are tested. In general, a protocol may address this through prespecified testing order, adjustment methods or another strategy. The multiplicity approach and testing hierarchy are not reported in the registry record. The record reports zero analyses, so there are no posted comparisons for which an adjustment can be checked.

The primary endpoint analysis was not performed because of early termination and insufficient participants or data for meaningful analyses. The record does not describe how missing measurements would have been handled, whether participants with incomplete follow-up were excluded or retained under a particular method, or how the participant who was assigned to active drug but not dosed would have been treated in the primary analysis. It notes variability in the number of doses received, but does not specify an analysis to account for that variation.

The planned analysis populations are not reported in the registry record. In general, an intention-to-treat population includes participants according to randomized assignment, while other analysis populations may require treatment receipt or additional eligibility criteria. These approaches answer different questions and can yield different estimates. No specific population definition can be attributed to this trial from the registry information.

The registry’s stated sample-size assumptions describe planning illustrations, not the trial’s documented original statistical plan. The original sample-size justification, missing-data procedures, interim analyses and multiplicity strategy are not reported in the registry record. With no primary analysis, none of these aspects can be evaluated against posted efficacy results.

11. Safety Results

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

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: carotid artery stenosis (50.0%).

The registry lists serious adverse events by study group. In the PF-04382923 2.5 mg/kg group, 1 of 2 participants at risk was affected. In the 7.5 mg/kg group, 0 of 3 were affected; in the 15.0 mg/kg group, 0 of 3 were affected; and in the placebo group, 0 of 2 were affected. The listed serious adverse event term is carotid artery stenosis, reported at 50.0%.

For other adverse events, the registry lists 2 of 2 participants affected in the 2.5 mg/kg group, 0 of 3 in the 7.5 mg/kg group, 1 of 3 in the 15.0 mg/kg group and 1 of 2 in the placebo group. These are small group counts. They describe what the registry records, but do not provide a precise estimate of comparative safety or establish that an event was caused by RN6G.

Deaths are not reported in the registry record. The adverse-event counts should not be interpreted as a complete characterization of risk, particularly given the small enrollment and early termination.

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

The record shows that a randomized, placebo-controlled phase 2 study of RN6G was conducted in participants with geographic atrophy secondary to age-related macular degeneration and was terminated after 10 participants enrolled. It also shows that the intended primary endpoint concerned the rate of geographic atrophy growth in the study eye at Day 309, measured using fundus autofluorescence. These registry entries describe the trial’s purpose and status, not its efficacy result.

The primary endpoint analysis was not performed, according to the registry, because early termination left insufficient participants or data for meaningful analyses. No primary treatment-effect estimate, uncertainty interval or p-value is reported. The posted record therefore does not quantify whether, or by how much, the groups differed on the intended endpoint. It also does not establish that there was no difference. An absent analysis is not evidence of a zero effect.

The listed secondary outcomes include measures of visual acuity, low-luminance visual acuity and contrast sensitivity. Their inclusion identifies other intended assessments, but the registry reports no analyses for them. Likewise, the adverse-event counts describe a small number of participants and cannot support a dependable comparison of safety between dose groups and placebo.

In general, evidence from a randomized trial depends not only on design features but also on usable outcome data and an analysis that matches a prespecified question. Randomization and masking are relevant design safeguards, but they do not create an interpretable estimate when the outcome analysis was not performed. The registry record does not report enough detail to assess the original analysis plan, missing-data strategy or multiplicity handling.

The defensible conclusion is therefore limited: the registry records an early-terminated trial with no meaningful primary endpoint analysis. It does not support a conclusion that RN6G did or did not affect geographic atrophy growth, nor does it establish comparative safety. Further conclusions would require evidence not reported in the registry record.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a carefully framed clinical question and an answer supported by analyzable data. The study was randomized, parallel-group and placebo-controlled, with masking recorded by the registry. Its intended primary endpoint was a structural measure of geographic atrophy progression. Yet the registry states that the primary analysis was not performed because there were too few participants or data for meaningful analysis.

That distinction is important when reading trial records. A protocol’s planned outcomes identify what investigators intended to measure; they do not show that those outcomes were successfully measured or analyzed. Likewise, an intervention’s assigned dose groups do not establish that participants received consistent exposure. The registry notes that one participant assigned to active drug was not dosed and that the number of doses received varied.

The record also shows why counts from very small groups need cautious interpretation. A single participant can constitute a large share of a small group, while the estimate remains highly uncertain. The adverse-event figures are therefore useful as a description of recorded events, not as strong evidence for differences between treatment groups. The primary efficacy outcome offers no estimate at all.

More broadly, this record highlights the role of transparency about analysis plans. Details such as the intended analysis population, missing-data handling, multiplicity strategy and sample-size justification help readers judge whether a reported comparison is appropriate and precise. Those details are not reported in the registry record, and the absence of a primary analysis means that many of these questions cannot be resolved by examining results.

The statistical lesson is not that an early-terminated trial has no informational value. The record documents the study’s intended question, enrollment, status and reported safety counts. But it also demonstrates that design intent and trial results are not interchangeable. Without an analyzable primary outcome, the central efficacy question remains unanswered by this record.

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 primary limitation is that the registry says the primary endpoint analysis was not performed. It attributes this to early termination and an insufficient number of participants or amount of data for meaningful analyses. There is consequently no reported primary endpoint estimate, treatment comparison or measure of uncertainty.

Enrollment was 10. The registry notes that eight participants were assigned to active drug, including one who was not dosed, and that the number of doses received varied. The arm descriptions do not provide details that would allow the extent or consequences of this variation to be assessed. The reason for termination is not reported in the registry record.

The registry lists 33 outcome measures but reports zero analyses. It does not report results for the listed visual-function and contrast-sensitivity outcomes. Nor does it report the original sample-size justification, planned analysis populations, missing-data methods, multiplicity strategy or interim analyses. These omissions prevent readers from assessing how the study intended to manage incomplete measurements and multiple outcomes.

The descriptions of masking are not identical: the official title calls the study double-masked, while the registry classifies it as quadruple. The record does not explain this difference or identify which roles were masked. The method of randomization and allocation concealment are also not reported.

Safety information is limited by the small group counts and the absence of reported deaths. The adverse-event figures are descriptive and cannot establish causation or provide a precise comparison between treatment groups. Overall, the registry supports a description of the trial and its limitations, but not a meaningful efficacy assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy, Safety And Tolerability Study Of RN6G In Subjects With Geographic Atrophy Secondary to Age-related Macular Degeneration — NCT01577381.
• Registry record last updated 2016-03-16; status last verified 2016-02.
• Results first posted 2016-03-16.
• 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

NCT01577381 is a phase 2 randomized, parallel-group, placebo-controlled study of RN6G in participants with geographic atrophy secondary to age-related macular degeneration. The official title describes a multicenter, double-masked, multidose study; the registry classifies masking as quadruple. The record lists PF-04382923 dose groups of 2.5 mg/kg, 7.5 mg/kg and 15.0 mg/kg, alongside placebo.

The recorded start was 2012-08, and primary completion was 2013-09. The study status is terminated, with 10 participants enrolled. The intended primary endpoint was the mean reduction in the rate of geographic atrophy growth in the study eye at Day 309, based on fundus autofluorescence. The registry says the analysis was not performed because early termination left insufficient participants or data for meaningful analyses.

The record lists 33 outcome measures and reports zero analyses. It includes descriptive adverse-event counts, but no primary efficacy estimate. The reason for termination and several details of the statistical plan are not reported in the registry record.