Safety, Tolerability and Evidence of Activity Study of UBX1325 in Patients With Diabetic Macular Edema (BEHOLD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Evidence of Activity Study of UBX1325 in Patients With Diabetic Macular Edema (BEHOLD) (NCT04857996), a randomized phase 2 study. The primary outcome is Systemic Safety and Tolerability of a Single IVT Injection of UBX1325..

2. Clinical Question

3. Trial Design

BEHOLD is described in the registry record as a phase 2a, prospective, multicenter, randomized, double-masked, sham-controlled study with a parallel-group design. It evaluated a single intravitreal injection of UBX1325 against sham in patients with diabetic macular edema. The registered enrollment is 65. The study status is completed; the recorded start date is 2021-06-25 and the primary completion date is 2023-04-06.

The sponsor is Unity Biotechnology, Inc. The stated purpose was to assess exposure, safety, biological activity, and durability of UBX1325 and its active parent molecule, UBX0601, following treatment. The primary outcome is systemic safety and tolerability through TEAEs classified by system organ class and preferred term, with a timeframe of 48 weeks. Changes in best corrected visual acuity from baseline are identified as a secondary outcome.

Randomization and double masking describe the broad design, but the registry record does not report the randomization sequence, allocation concealment, masking procedures, or whether masking was assessed. It does not report the planned allocation ratio or any stratification factors. The available safety counts use groups of 33 for sham and 32 for UBX1325 as the numbers at risk for serious adverse events. Those risk-set counts describe the posted safety data and should not be treated as a complete account of all aspects of trial allocation or follow-up.

The registry record lists three outcome measures and zero analyses. It does not provide a single primary-outcome comparison reduced to one result, and the record indicates that the primary outcome has several categories or time points. Consequently, the design can be described, but a direct estimate of the primary outcome contrast cannot be reconstructed from the listed information.

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: each participant contributed only one study eye

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set includes all patients who received a single IVT treatment of UBX1325 or sham. Summary statistics are frequency (percentage of column total).

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 Systemic Safety and Tolerability of a Single IVT Injection of UBX1325., measured over 48 weeks.

The primary endpoint is systemic safety and tolerability after a single intravitreal injection of UBX1325. It is measured as the incidence of treatment-emergent adverse events, grouped by system organ class and preferred term, over 48 weeks. The stated unit is participants, and the registry describes the summary statistics as frequencies, with percentages of the column total. The Safety Analysis Set includes patients who received a single intravitreal treatment of UBX1325 or sham.

Counting participants with events is a way to describe how often adverse events were observed in the treated groups. Classification by system organ class and preferred term can distinguish broad event categories from specific event descriptions. The endpoint is relevant to the stated safety and tolerability objective; it is not an efficacy endpoint. The registry record also lists change in best corrected visual acuity from baseline as a secondary outcome, but it does not give a numerical result for that outcome in the available information.

The primary outcome is not presented as a single treatment-versus-sham estimate. The record notes that it has several categories or time points and is not reduced to one comparison. The listed serious adverse-event counts therefore offer limited safety information, not a complete account of the primary endpoint across all event categories.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives the broad design and endpoint definition, but it does not report a detailed statistical analysis plan. The distinction matters: a design description explains how a study is organized, while an analysis plan specifies how outcomes will be summarized, compared, and interpreted. The available information supports a descriptive reading of the listed counts, not reconstruction of an unreported inferential analysis.

What does a participant count describe?

For an outcome expressed as participants with an event, a count records how many people met the event definition in the group being described. A denominator identifies how many people were considered at risk or included in that summary. Here, serious adverse-event counts are reported with numbers at risk for each group. Such counts describe observed events in the recorded groups; they do not, without further analysis, quantify the uncertainty around a treatment comparison.

The primary outcome description says that summary statistics are frequencies, with percentages of the column total. In general, a frequency summary is useful for displaying how event reports are distributed across categories. Its interpretation depends on the category definitions, the population included, and the denominator used. The primary endpoint specifies classification by system organ class and preferred term, but the registry information does not provide a complete category-by-category treatment comparison or enough detail to assess all denominators for the listed serious-event terms.

Why would a comparison need more than counts?

A difference between group counts can reflect a treatment contrast, random variation, or features of the observed data such as unequal numbers of participants at risk. Statistical inference is used to quantify how uncertain a comparison is under a specified model. A confidence interval is a general way to express the range of effect estimates compatible with the data and assumptions; a narrow interval indicates greater precision than a wide interval. No confidence interval for the primary outcome is reported in the registry record.

A p-value is a general measure of how compatible data are with a specified null model, given the analysis assumptions. It does not measure the probability that a treatment effect is true, and it does not describe the size or clinical importance of an effect. The registry record lists zero analyses, so it does not provide a p-value for the primary comparison. Without the analysis method and an estimate with its uncertainty, the serious-event counts should remain descriptive rather than being treated as a statistically established difference.

What does the endpoint structure imply?

The endpoint is described across system organ classes and preferred terms, and the record notes that the primary outcome has several categories or time points rather than a single comparison. In general, testing multiple outcomes or categories raises a multiplicity question: repeated testing can increase the chance of a chance-positive finding if each result is interpreted separately. Researchers may prespecify a hierarchy, adjustment, or other strategy to address this. Such a strategy is not reported in the registry record, so it is not possible to determine how multiple categories or time points were intended to be interpreted.

Adverse events may also occur more than once in a participant. A participant-level count and an event-level count answer different questions: the first concerns how many people experienced an event, while the second concerns how many event occurrences were recorded. The primary endpoint is stated in participants, but the registry does not provide the full analysis details needed to determine how recurrent events, event timing, or category overlap were handled. Those choices should not be inferred from the brief endpoint definition.

How should the planning assumptions be read?

The registry describes planning illustrations based on the observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the groups, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a report of the trial's original design rationale. The numerical sample-size illustrations are not stated in the registry information used for this interpretation. They should not be read as observed power or as evidence that the trial was designed around a particular effect size.

For a binary outcome, a planning calculation generally depends on the event rates being targeted and on assumptions about the comparison. The registry record does not report a sample-size justification, the assumed event rates, or the procedure used to select the original enrollment. The planning assumptions therefore cannot fill in the missing design rationale. In particular, the observed counts should not be used to imply that the study had adequate or inadequate power for a treatment difference.

What remains unreported?

The record does not state how missing outcome data were handled, how the analysis population for each outcome was defined beyond the Safety Analysis Set description, or whether any covariate adjustment was planned. It also does not report an interim-analysis plan or a detailed method for estimating and comparing event frequencies. These omissions limit reproducibility and prevent a fuller assessment of precision and bias. General statistical principles can explain why these details matter, but they do not justify supplying a method the record does not state.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and identifies changes in best corrected visual acuity from baseline as a secondary outcome. The primary outcome is described through TEAEs grouped by system organ class and preferred term, and the record notes that it has several categories or time points rather than one reduced comparison. The registry lists zero analyses. It does not report a multiplicity strategy, such as a testing hierarchy or adjustment across outcomes, categories, or time points. Without that information, the intended interpretation of any category-specific finding is not clear.

The Safety Analysis Set is defined as patients who received a single intravitreal treatment of UBX1325 or sham. The registry does not give comparable analysis-population definitions for the secondary outcome or other outcome measures. It also does not report how missing data, incomplete follow-up, treatment discontinuation, or outcomes not observed at a scheduled assessment were handled. These are relevant details because the included participants and the handling of missing observations can affect both group summaries and comparisons.

No statistical analysis plan, interim-analysis details, or sample-size justification are reported in the registry record. The planning assumptions that are described are illustrations based on the observed effect, not evidence of the original design rationale. In the absence of the missing analysis details, the posted serious-event counts can be interpreted descriptively, but they cannot support a complete assessment of multiplicity control, missing-data bias, or the primary analysis population.

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: anaemia (3.1%), atrial fibrillation (3.1%), coronary artery occlusion (3.1%), cellulitis (3.1%), pneumonia (3.1%).

For serious adverse events, the sham control group has 4 participants affected among 33 at risk; the UBX1325 group has 5 participants affected among 32 at risk. The registry records zero deaths in both groups. These figures are participant counts, not a complete description of all adverse events or a statistical comparison. The available information does not give a confidence interval or an adjusted estimate for the difference between groups.

The registry also lists anaemia, atrial fibrillation, coronary artery occlusion, cellulitis, pneumonia, and ankle fracture as serious adverse-event terms, each reported at 3.1%. The listed terms are not assigned to a specific treatment group in the available information, and their percentage denominator is not explained in those entries. They therefore should not be interpreted as group-specific percentages or combined into a total.

Serious adverse events are only part of the primary safety endpoint, which concerns TEAEs by system organ class and preferred term over 48 weeks. The serious-event figures should be read as descriptive safety information within the recorded groups, not as evidence that a treatment caused or prevented an event.

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

The registry record establishes that BEHOLD was a randomized, double-masked, sham-controlled study of UBX1325 in patients with diabetic macular edema, with systemic safety and tolerability as the primary outcome. The reported serious adverse-event counts and zero deaths provide descriptive information about the safety groups. The listed serious-event terms offer additional detail, although they are not linked to a treatment arm in the available entries.

Those data do not amount to a full primary-endpoint result. The endpoint covers TEAEs across system organ classes and preferred terms over 48 weeks, while the registry does not report a single primary comparison, a full category-level summary, or inferential analyses. The record also does not give a numerical result for the secondary outcome of change in best corrected visual acuity from baseline. Therefore, the available information does not establish the magnitude or precision of a treatment contrast for either endpoint.

Counts should not be interpreted as proof of a difference or proof of equivalence. A small difference in observed counts may be compatible with considerable uncertainty, while the absence of an inferential result cannot be taken to mean there was no difference. The registry record does not report the uncertainty estimates needed to judge the range of plausible comparative effects.

The study's stated aims included exposure, biological activity, and durability, in addition to safety. The registry information does not provide numerical results for those aims. The appropriate interpretation is limited to the design and the safety counts that are explicitly recorded, with the remaining outcome questions unresolved by the available registry information.

13. Why This Trial Matters Statistically

BEHOLD is statistically notable because its primary outcome is a safety endpoint with multiple event categories and time points, while the registry does not reduce those categories to a single comparison. This makes clear why endpoint definitions and analysis plans matter: counts can be easy to state, but interpreting them requires knowing which events are included, the population used, the denominator, and how comparisons across categories are handled.

The record's randomized, double-masked, sham-controlled design is relevant to how a treatment comparison could be evaluated. Randomization is generally intended to support comparability between groups, and masking can reduce some forms of bias. However, those design features do not remove uncertainty from the observed data or replace reporting of estimates and their precision. Details of allocation and masking procedures are not reported in the registry record.

The posted serious-event counts make the distinction between descriptive and inferential statistics concrete. They indicate how many participants were recorded with serious adverse events in each safety group, but do not quantify the uncertainty of a treatment contrast. The absence of listed analyses and a single primary comparison limits what can be concluded from the record.

The registry also gives planning assumptions for sample-size illustrations, including a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations concern future planning under stated assumptions; they are not observed power and do not explain the original enrollment rationale. Overall, the trial is a useful example of why transparent reporting of endpoint-level results, denominators, missing-data handling, and multiplicity methods is needed to move from event counts to a statistically interpretable treatment comparison.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation is that the registry record does not present the primary safety outcome as a single treatment comparison. The endpoint is described across system organ classes and preferred terms, and the record notes multiple categories or time points. Although serious adverse-event counts are available, they do not provide the complete TEAE profile described by the primary endpoint.

The serious-event terms are listed with percentages but are not linked to a treatment group in the available entries, and the percentage denominator is not specified there. The record does provide group-level numbers at risk, affected counts, and deaths, but it does not provide a comparative estimate or uncertainty interval. These differences in reporting detail limit interpretation of the term-level entries.

The registry lists zero analyses and does not report a detailed statistical plan, multiplicity handling, or missing-data methods. It also does not provide results for the secondary change in best corrected visual acuity from baseline, or numerical findings for exposure, biological activity, or durability. The Safety Analysis Set is defined for patients who received treatment, but the registry does not explain analysis populations for other outcomes.

Details of eligibility criteria, allocation procedures, masking implementation, follow-up completeness, and the original sample-size rationale are not reported in the registry record. These omissions make it difficult to evaluate generalizability, potential sources of bias, and the precision of the treatment comparison. The available information supports a limited descriptive account rather than a complete statistical assessment of the trial's outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability and Evidence of Activity Study of UBX1325 in Patients With Diabetic Macular Edema (BEHOLD) — NCT04857996.
• Registry record last updated 2024-05-16; status last verified 2024-04.
• Results first posted 2024-05-16.
• 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

BEHOLD (NCT04857996) is a completed phase 2a, prospective, multicenter, randomized, double-masked, sham-controlled, parallel-group study sponsored by Unity Biotechnology, Inc. It enrolled 65 patients with diabetic macular edema and evaluated a single intravitreal injection of UBX1325 against sham. The recorded study start date is 2021-06-25, and the primary completion date is 2023-04-06.

The primary outcome is systemic safety and tolerability through TEAEs by system organ class and preferred term over 48 weeks. The registry lists changes in best corrected visual acuity from baseline as a secondary outcome. Serious adverse-event counts were 4 of 33 at risk for sham and 5 of 32 at risk for UBX1325, with zero deaths in each group. The record lists zero analyses and does not report a single primary-outcome comparison or a numerical result for the secondary visual-acuity outcome.