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 Study of Innovative Multimodal Imaging Biomarkers to Predict Anatomical Outcome in Naive Patients With wAMD Treated With Brolucizumab. (NCT04774926), a na phase 4 study. The primary outcome is Number of Patients Classified as q12w Fluid-free or Not q12w Fluid-free.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04774926 |
| Phase | Phase 4 |
| Condition | Neovascular Age-related Macular Degeneration |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 122 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients with neovascular age-related macular degeneration, described in the study title and summary as wet age-related macular degeneration. The primary outcome population was the Full Analysis Set: participants who received at least one dose and had a valid measurement without a protocol deviation with impact. Participants with protocol deviations were excluded from this population.
Intervention
Brolucizumab 6 mg, given as three monthly ocular injections followed by maintenance treatment. The maintenance schedule was q12w or q8w according to disease activity.
Comparator
There was no separate comparator group. The study used a single-group, open-label design, so its outcome categories do not represent a randomized comparison between treatment arms.
Primary question
By Week 48, how many participants met the registry definition of q12w fluid-free: completing treatment and the study on a stable q12w regimen assigned at Week 16, with no intraretinal or subretinal fluid on spectral-domain optical coherence tomography? The other category included participants with fluid at Week 48, those who used a q8w regimen at any time, and those who discontinued treatment or the study after baseline. The counts for these categories are not reported in the registry record.
The study aimed to identify early imaging features that could predict fluid resolution later in follow-up. Its stated purpose was to assess whether early imaging parameters might support decisions about the q12w or q8w treatment regimen. This is a prediction-oriented question: it asks whether early measurements are associated with a later outcome, rather than whether brolucizumab is better than another treatment. Because there is no comparator group, the study cannot estimate a between-treatment difference. The registry record describes imaging outcomes through Week 48, including optical coherence tomography angiography features and spectral-domain optical coherence tomography features. The primary outcome is a combined classification of retinal fluid status, treatment regimen, and study completion. Results for the primary classification are not reported in the registry record, so the frequency of either category and the strength of any early imaging prediction cannot be assessed from the posted results described in the record.
3. Trial Design
This was a Phase IV, single-group, open-label, multicenter study. The registry lists an enrollment of 122 participants and describes brolucizumab 6 mg as the intervention. There was no randomized allocation and no separate control group. Participants received three monthly ocular injections, then entered a maintenance phase with q12w or q8w treatment determined by disease activity. The registry record lists the study as completed. The study start date was 2021-10-15, and primary completion was 2023-10-04.
The design was intended to examine early multimodal imaging parameters as predictors of later anatomical response, particularly fluid resolution. The primary outcome was assessed up to Week 48 and used spectral-domain optical coherence tomography to classify participants as q12w fluid-free or not q12w fluid-free. That classification did not depend only on fluid status at the final assessment: use of q8w treatment at any time, treatment discontinuation, or study discontinuation after baseline also placed a participant in the not q12w fluid-free category. This definition combines anatomical status with treatment course and retention in the study.
The registry lists 42 outcome measures and no analyses. It identifies multiple secondary imaging outcomes, including changes in lesion area, vascular density, lesion diameter, and other OCTA or SD-OCT features from baseline up to Week 48. Numerical results for these outcomes are not reported in the registry record. The record does not report a statistical analysis plan, sample-size justification, or details of how early imaging features were evaluated as predictors. The absence of a control group and the open-label design are central to interpreting the results: the study describes outcomes within participants receiving the study regimen, not a causal treatment contrast against an alternative.
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: If both eyes were eligible as per the inclusion and exclusion criteria, only one eye was treated during the study, with the eye with the worse visual acuity (BCVA) at Baseline selected as the study eye. If both eyes had the same BCVA, the right eye was chosen as the study eye.
Overall Study
| Stage | Brolucizumab 6 mg |
|---|---|
| STARTED | 122 |
| COMPLETED | 91 |
| NOT COMPLETED | 31 |
Reasons for not completing this period:
| Reason | Brolucizumab 6 mg |
|---|---|
| Adverse Event | 15 |
| Lost to Follow-up | 3 |
| Physician Decision | 6 |
| Withdrawal by Subject | 3 |
| The original PI resigned and a new one could not be appointed | 4 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set - includes all patients who received at least one dose of the study drug and with a valid measurement without a protocol deviation with impact. (Excludes patients with protocol deviations.)
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 | Brolucizumab 6 mg |
|---|---|---|
| Participants analysed | 122 | |
| Age, Continuous | Years | 76.1 (SD 7.88) |
| Sex: Female, Male: Female | Participants | 72 |
| Sex: Female, Male: Male | Participants | 50 |
| 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 | 122 |
| 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 Number of Patients Classified as q12w Fluid-free or Not q12w Fluid-free, measured over Up to Week 48.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants assigned to one of two categories up to Week 48: q12w fluid-free or not q12w fluid-free. A participant met the q12w fluid-free definition if they completed treatment and the study, maintained the stable q12w regimen assigned at Week 16 through Week 48, and had neither intraretinal nor subretinal fluid at Week 48 on spectral-domain optical coherence tomography.
The second category included several distinct situations: fluid at Week 48, use of a q8w regimen at any point, discontinuation of treatment after baseline, or discontinuation from the study after baseline. The registry explicitly treats the latter events as failures for this endpoint. Therefore, the outcome is not simply a count of participants with no retinal fluid at the final visit. It reflects both anatomical findings and the ability to remain on the specified regimen and complete follow-up.
This kind of endpoint can be useful for evaluating a clinically relevant treatment pattern alongside imaging status, but its interpretation depends on the precise category definition. Participants may be classified as not q12w fluid-free for different reasons, and the combined count does not by itself distinguish those reasons. The registry gives the endpoint definition and timeframe, but the numbers in each category are not reported in the registry record. Neither an observed proportion nor uncertainty around that proportion can therefore be described from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a single-group study designed to examine early imaging parameters as predictors of fluid resolution in patients treated with brolucizumab. Its primary endpoint is a binary participant classification at Week 48, but the category counts are not reported in the registry record. As a result, the posted information does not establish how many participants were q12w fluid-free, how many were classified as not q12w fluid-free, or how precise either estimate would be. No treatment effect estimate or statistical test for the primary endpoint is reported in the registry record.
The endpoint definition matters when interpreting any reported count. The q12w fluid-free category requires absence of both intraretinal and subretinal fluid, continued stable q12w treatment from the assignment at Week 16 through Week 48, and completion of treatment and the study. The other category combines fluid at Week 48 with q8w treatment at any time and post-baseline discontinuation. These components represent different clinical and study-course events. A combined category gives a summary of the prespecified classification, but it cannot reveal the separate contribution of each reason unless those components are reported individually.
There is no concurrent comparator group. Therefore, even if a within-group fluid-free count were available, it would describe outcomes in this study population under the study regimen. It would not show how those outcomes compare with another treatment or with a different treatment schedule. The open-label design also means treatment and assessment were not masked according to the registry. The primary outcome uses imaging, but the record does not report details of image reading or assessment procedures beyond the named modality.
The study is framed around prediction from early imaging, yet the registry record does not report the predictive results, a model specification, measures of predictive accuracy, or validation procedures. It also does not report confidence intervals or p-values for the primary outcome. The record lists 42 outcome measures and no analyses, while the available description identifies several imaging outcomes. Their numerical results are not reported in the registry record. This leaves the central questions about the observed imaging patterns and their association with later fluid resolution unanswered in the registry record.
Safety information is reported separately from the primary anatomical outcome. Among 122 participants at risk in the brolucizumab group, 14 had a serious adverse event and 52 had other adverse events; deaths were reported as 0. The registry also lists serious-event terms with percentages. These counts describe events in the treated study group and do not provide a comparison with an untreated or alternative-treatment group. They should not be read as evidence about comparative safety or as proof that a particular event was caused by treatment.
9. Statistical Methods Explained
The primary outcome is a binary classification: each participant is placed in one of two categories. In general, a binary outcome is often summarized by the count in each category and the proportion in each category. A confidence interval, in general, describes the statistical uncertainty around an estimate under the assumptions of the method used. The registry record does not report the primary category counts, proportions, confidence intervals, or p-values. Without those results, the observed rate and its precision cannot be evaluated.
What does the endpoint classify?
The endpoint labels are based on more than the Week 48 scan. To qualify as q12w fluid-free, participants had to complete treatment and the study, maintain the stable q12w regimen assigned at Week 16 through Week 48, and have no intraretinal or subretinal fluid at Week 48 according to spectral-domain optical coherence tomography. The not q12w fluid-free category included participants with fluid at Week 48, anyone who followed the q8w regimen at any time, and anyone who discontinued treatment or the study after baseline. This operational definition determines how each participant contributes to the count; it should not be replaced with a simpler interpretation based on fluid alone.
What does the single-group design allow?
In general, a single-group study can describe outcomes observed in the enrolled group, but it does not directly estimate a difference from a concurrent control group. The registry lists allocation as not applicable and the model as single group. There is no like-for-like randomized comparison. Consequently, a result from this design would not distinguish the effect of the intervention from other influences that may affect outcomes over the study period. A prediction question is also distinct from a treatment-comparison question: prediction concerns whether measured features anticipate a later outcome, while a treatment comparison concerns differences between assigned interventions.
How should the imaging prediction aim be assessed?
In general, assessing a prediction model requires information about how predictors were measured and selected, how the model was constructed, and how well it predicts outcomes in the data used for assessment. Measures of predictive performance and validation can help show whether an apparent relationship is useful beyond the data used to develop it. The registry record does not report a model specification, predictor-selection method, validation approach, or numerical prediction-performance results. It therefore does not support a judgment about the accuracy or generalizability of an early-imaging prediction.
What do the imaging outcomes cover?
The registry lists secondary outcomes involving OCTA features from baseline up to Week 48, including branching vessels, total choroidal neovascularization lesion area, vascular density, greatest linear diameter, peripheral anastomotic arcades, vascular loops, and dark halo. It also lists a spectral-domain OCT feature concerning pigment epithelial detachment. These are anatomical or imaging measures, but the numerical outcome results are not reported in the registry record. The record does not state how missing imaging measurements were handled or how repeated measurements over time were modeled.
What is the role of uncertainty and statistical testing?
In general, a point estimate gives a central summary of an outcome, while an interval estimate communicates uncertainty around it. A p-value, when used, addresses compatibility between data and a statistical hypothesis under specified assumptions; it does not measure clinical importance or the probability that a hypothesis is true. No primary endpoint estimate, uncertainty interval, or test result is reported in the registry record. No inferential conclusion about the primary classification can be drawn from the endpoint definition alone.
What do the planning illustrations mean?
The registry record does not report the trial's own sample-size justification. Any sample-size planning illustrations based on an observed effect are not the trial's original design rationale and are not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. The record's actual study was single group, so a two-arm illustration is not a description of the treatment allocation used in this study. Such calculations are planning examples, not evidence that the trial had a particular probability of finding a result. The effect values and resulting planning sample sizes are not reported in the registry record.
Finally, general statistical interpretation depends on the analysis population and handling of events such as discontinuation. The primary outcome population is described as the Full Analysis Set, which included participants who received at least one dose and had a valid measurement without a protocol deviation with impact, while excluding participants with protocol deviations. The endpoint also classifies treatment and study discontinuation after baseline as not q12w fluid-free. The record does not report further details of missing-data methods or analysis procedures.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 42 outcome measures and names multiple secondary imaging outcomes. When many outcomes are examined, the chance of finding apparently notable results by chance can increase if each is tested separately. In general, multiplicity procedures can control or describe this issue, but their choice depends on the intended hypotheses and analysis plan. Any multiplicity adjustment or hierarchy of outcomes is not reported in the registry record. The record lists no analyses, and does not provide numerical results or inferential tests for the imaging outcomes.
The Full Analysis Set is defined as participants who received at least one dose and had a valid measurement without a protocol deviation with impact; participants with protocol deviations were excluded. The registry does not report the number included in this set or the reasons for exclusion. The primary endpoint definition assigns post-baseline treatment or study discontinuation to the not q12w fluid-free category. This is an explicit endpoint rule, not a general description of how other missing observations or incomplete imaging data were handled.
Specific methods for missing data, incomplete follow-up, unavailable scans, or missing secondary outcome measurements are not reported in the registry record. The registry also does not report sensitivity analyses, a detailed statistical analysis plan, or whether analyses used any other populations. These gaps limit assessment of how the reported population and endpoint definition would affect estimates, even apart from the absence of primary outcome counts.
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 |
|---|---|---|---|
| Brolucizumab 6 mg | 14 | 122 | 11.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Brolucizumab 6 mg | 0 of 122 |
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 |
|---|---|
| Brolucizumab 6 mg | 52 of 122 |
Most frequent serious adverse event terms
| Event term | Organ system | Brolucizumab 6 mg |
|---|---|---|
| Cerebrovascular accident | Nervous system disorders | 2 of 122 |
| Acute myocardial infarction | Cardiac disorders | 1 of 122 |
| Retinal occlusive vasculitis- Study eye | Eye disorders | 1 of 122 |
| Uveitis- Study eye | Eye disorders | 1 of 122 |
| Intestinal obstruction | Gastrointestinal disorders | 1 of 122 |
| Asthenia | General disorders | 1 of 122 |
| Condition aggravated | General disorders | 1 of 122 |
| Fall | Injury, poisoning and procedural complications | 1 of 122 |
| Joint dislocation | Injury, poisoning and procedural complications | 1 of 122 |
| Acute undifferentiated leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 122 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Brolucizumab 6 mg |
|---|---|---|
| COVID-19 | Infections and infestations | 13 of 122 |
| Vitritis- Study eye | Eye disorders | 5 of 122 |
| Influenza | Infections and infestations | 4 of 122 |
| Macular hole- Study eye | Eye disorders | 3 of 122 |
| Neovascular age-related macular degeneration- Fellow eye | Eye disorders | 3 of 122 |
| Retinal pigment epithelial tear- Study eye | Eye disorders | 3 of 122 |
| Cataract- Study eye | Eye disorders | 2 of 122 |
| Eye inflammation- Study eye | Eye disorders | 2 of 122 |
| Macular fibrosis- Study eye | Eye disorders | 2 of 122 |
| Retinal tear- Study eye | Eye disorders | 2 of 122 |
Serious events with the highest arm-level rate: cerebrovascular accident (1.6%), acute myocardial infarction (0.8%), retinal occlusive vasculitis- study eye (0.8%), uveitis- study eye (0.8%), intestinal obstruction (0.8%).
For the Brolucizumab 6 mg group, 122 participants were listed as at risk for serious adverse events and 14 participants were listed as affected. The number listed as at risk for other adverse events was also 122, with 52 affected. Deaths were reported as 0. These are counts within the treated study group; the registry record does not include a separate comparator group for interpreting differences in safety outcomes.
The registry lists the following serious adverse event terms and percentages: cerebrovascular accident, 1.6%; acute myocardial infarction, 0.8%; retinal occlusive vasculitis in the study eye, 0.8%; uveitis in the study eye, 0.8%; intestinal obstruction, 0.8%; and asthenia, 0.8%. These term-level percentages describe the registry entries and should not be added together to infer a total, since the record does not state whether participants could contribute to more than one term. The percentages also do not establish causation. The record does not report a comparative safety estimate or additional detail on timing, severity beyond the serious-event classification, or attribution for these terms.
12. What the Result Does, and Does Not, Mean
The registry record describes a study intended to evaluate whether early imaging features could predict a later fluid-free outcome among patients receiving brolucizumab. It also defines a specific Week 48 classification that combines retinal fluid status with treatment regimen and study completion. These details clarify the question the study set out to address, but the record does not report the primary category counts or numerical results for the imaging outcomes. The observed frequency of q12w fluid-free status and the precision of any estimate cannot be stated.
Even with numerical results, a single-group, open-label study would describe outcomes in the enrolled group rather than establish a comparative effect against another treatment. The registry lists no comparator. The endpoint's combined definition also means that a not q12w fluid-free count would not, by itself, distinguish participants with fluid from participants who changed to q8w treatment or discontinued. Separate component results would be needed to understand those different pathways.
The study's predictive aim cannot be evaluated from the endpoint definition alone. Evidence about prediction would require reported results connecting early imaging measurements to the later outcome, along with details of model performance and validation. Those results and methods are not reported in the registry record. Likewise, the safety counts describe events among participants in the treated group and do not establish a comparative safety profile or treatment causality.
Accordingly, the registry record conveys the study design, endpoint definition, analysis population description, and selected safety counts, but not the primary efficacy results or numerical imaging findings. It supports an account of what was measured and how the primary outcome was classified, not a conclusion about the observed predictive performance or comparative clinical effects.
13. Why This Trial Matters Statistically
This study is statistically notable for joining early imaging measurements to a later anatomical classification. That structure raises a prediction question rather than only a question about average change over time: the aim was to assess whether early parameters could anticipate fluid resolution by Week 48. In general, prediction requires a clear outcome definition and careful reporting of how imaging features relate to that outcome. The registry defines the outcome but does not report the predictive analyses or their results.
The endpoint also illustrates why operational definitions matter. Its q12w fluid-free category requires both the specified imaging status and maintenance of the q12w regimen through follow-up. Conversely, the other category includes fluid, q8w treatment at any time, and discontinuation after baseline. The resulting count would summarize a clinically and analytically specific pathway, rather than fluid status in isolation. Reporting the reasons for classification separately would help distinguish anatomical findings from regimen changes and follow-up events, but such component results are not reported in the registry record.
The single-group design places an important boundary on interpretation. It can be used to describe outcomes and explore associations within the enrolled group, but it does not provide a randomized treatment comparison. The open-label approach and absence of a control group should therefore be considered alongside the study's prediction aim. Further, the record lists 42 outcome measures and no analyses, while the numerical results and multiplicity approach are not reported. This prevents readers from judging the evidence across the several imaging outcomes or the strength and reproducibility of any prediction. The design and endpoint are informative; the missing outcome and analysis results limit what can be concluded from the registry 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 principal limitation for interpretation is that the registry record does not report the primary endpoint counts or the numerical results for the imaging outcomes. This prevents assessment of the observed Week 48 classification, its precision, and the stated early-prediction aim. The record lists 42 outcome measures but no analyses, and does not report a statistical analysis plan, model details, validation procedures, or multiplicity methods.
The design has no separate comparator group and is open label. Outcomes therefore cannot be interpreted as a randomized comparison with another treatment or schedule. The endpoint also combines multiple reasons for being classified as not q12w fluid-free: fluid at Week 48, q8w treatment at any time, or discontinuation of treatment or the study after baseline. Without separate component counts, the contribution of each reason is not reported.
The analysis population excludes participants with protocol deviations and requires a valid measurement after at least one dose. The registry does not report how many participants were included in that population, how many were excluded, or details of missing imaging data and other missing-data handling. The record does not report the trial's sample-size justification, interim analyses, or further analysis procedures. These limitations are specific to the information in the registry record and make it difficult to assess the precision, robustness, and reproducibility of the intended analyses.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Innovative Multimodal Imaging Biomarkers to Predict Anatomical Outcome in Naive Patients With wAMD Treated With Brolucizumab. — NCT04774926.
- Registry record last updated 2025-05-16; status last verified 2025-05.
- Results first posted 2025-02-24.
- 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
NCT04774926, the IMAGINE Study, was a completed multicenter, open-label, single-group Phase IV study of brolucizumab 6 mg in neovascular age-related macular degeneration. The registry lists enrollment of 122 participants, with three monthly ocular injections followed by q12w or q8w maintenance according to disease activity. The study start date was 2021-10-15, and primary completion was 2023-10-04.
The primary outcome classified participants through Week 48 as q12w fluid-free or not q12w fluid-free, using retinal fluid status, treatment regimen, and study completion. The registry lists 42 outcome measures and no analyses. Primary outcome counts and numerical imaging results are not reported in the registry record. In the safety entries, 14 of 122 participants were affected by serious adverse events, 52 of 122 by other adverse events, and deaths were reported as 0.