Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy (GO): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy (GO) (NCT03922321), a na phase 2 study. The primary outcome is Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Serious AE (SAE), Treatment-related Adverse Event (AE), and Death During the 6-week Treatment Period.

2. Clinical Question

The study also included outcomes concerning proptosis, RVT-1401 concentrations, and anti-RVT-1401 antibodies. Those outcomes address clinical measurements and pharmacodynamic or pharmacokinetic features, rather than the primary safety count. The record lists 7 enrolled participants. It does not describe a placebo or active-comparator group, so the study cannot estimate a between-group treatment contrast. Its open-label, single-group design is suited to describing observations made during treatment, but it does not isolate the effect of treatment from changes that might occur over time or from other influences. The registry record does not report eligibility criteria beyond the condition and severity stated in the study title, or a detailed rationale for the selected dose schedule.

3. Trial Design

This was a Phase 2a, multicenter, open-label study of RVT-1401 for moderate to severe active Graves' Ophthalmopathy. The registry record describes a single-group design, with no allocation to competing study arms and no masking. Enrollment was 7. The study began on 2019-04-22, had a primary completion date of 2020-02-29, and is recorded as completed. These dates describe the registry record; they do not, by themselves, establish when each participant began or completed treatment.

Participants received RVT-1401 subcutaneously: 680 mg weekly for two weeks followed by 340 mg weekly for four weeks. The primary endpoint timeframe runs from baseline up to Week 6. The primary completion date is a study-level milestone, whereas an endpoint timeframe describes when participant outcomes were assessed; these are different kinds of information.

Open-label means that treatment masking was not used. A single-group study can describe safety events and other outcomes observed among participants receiving the intervention, but it does not provide a concurrent untreated or alternative-treatment group for comparison. This design therefore cannot separate treatment-associated changes from background variation, time trends, or other influences. The record lists secondary outcomes for proptosis at Week 7, overall proptosis response, RVT-1401 exposure measures, and anti-RVT-1401 antibodies at Week 7.

The registry record does not report a randomized allocation procedure, a masking procedure, or a control condition. Detailed site information, participant characteristics, eligibility criteria, treatment adherence, and reasons for any discontinuation are not reported in the registry record. A sample-size justification and the rationale for the dose schedule are also not reported in the registry record.

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: A total of 8 participants were screened for the study. Only 7 participants were randomized; 1 participant failed to meet the screening criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population: all participants who received at least one dose of study treatment

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 Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Serious AE (SAE), Treatment-related Adverse Event (AE), and Death During the 6-week Treatment Period, measured over from Baseline up to Week 6.

The primary endpoint concerns the number of participants with any treatment-emergent adverse event (TEAE), serious adverse event (SAE), treatment-related adverse event, and death during the 6-week treatment period. An adverse event is defined in the registry record as an untoward medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related to that product. A TEAE is defined by its timing relative to study dosing, with the record also specifying how events without a recorded start date are handled.

SAEs are distinguished by their seriousness, including outcomes such as death, life-threatening events, hospitalization, disability, congenital anomaly, or an important medical event that may require intervention. Seriousness is not the same as whether an event is considered related to treatment. An event can be serious or non-serious, and treatment relationship is a separate judgment.

Counting participants with events is a descriptive safety measure. It indicates how many participants in the safety population experienced events under the registry definitions; it does not measure event severity beyond the separate serious-event classification, duration, or change in symptoms. The safety population is defined as participants who received at least one dose of study treatment. The registry record does not provide a separate reported count for every element named in the primary endpoint. Such counts should not be inferred from the overall adverse-event figures.

This endpoint is used to characterize observed safety outcomes during the specified treatment period. In a single-group, open-label study, it cannot establish how the event frequency compares with what would have occurred without treatment or with another treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a count of participants who experienced specified safety events. For a count endpoint, the central descriptive information is the number of participants with an event and the number considered at risk or eligible for observation. These counts are not measurements of event intensity, and they do not indicate how long an event lasted. The registry record reports 7 participants at risk, 7 with other adverse events, 0 with serious adverse events, and 0 deaths in the RVT-1401 group.

The event definitions determine what qualifies for inclusion. The registry record defines an adverse event broadly as an untoward medical occurrence temporally associated with use of a medicinal product, regardless of whether it is considered related to that product. A TEAE is identified by timing relative to the first and last doses, with a specified rule for events that lack a recorded start date. These rules help standardize which events are counted, but they do not establish that treatment caused an event. The treatment-related category instead reflects an assessment of relationship, and its separate participant count is not reported in the registry record.

Seriousness is a classification based on consequences or medical importance. The record's definition includes death, life-threatening events, hospitalization or its prolongation, disability or incapacity, congenital anomaly or birth defect, and certain important medical events. Seriousness and treatment relationship are different dimensions: seriousness describes the event's consequences, while relatedness concerns its assessed connection to the medicinal product. Readers should not interpret a count of serious events as a count of treatment-related events.

For binary event outcomes, a participant is generally classified as having or not having the specified event during the observation window. The displayed count is useful for describing the study group, but an event count is not equivalent to a rate per unit of follow-up time. A rate would require information about the accumulated observation time, which is not reported in the registry record. Nor does a participant count show how many separate events occurred in a participant. The registry record's primary outcome is framed as the number of participants with events.

In general, uncertainty around a proportion or event frequency can be expressed with a confidence interval. The interval reflects both the observed data and the method used to estimate uncertainty. When the observed group is small, estimates can be imprecise; a zero count does not remove that uncertainty. The registry record does not report confidence intervals for these safety counts. It also does not report a hypothesis test for the primary safety outcome. Without such inferential results, the interpretation should remain descriptive rather than framed as a statistically demonstrated difference.

The study design affects which analyses are meaningful. In a randomized comparison, outcomes can be contrasted across allocated groups, subject to the design and analysis assumptions. This study is recorded as single-group, with allocation not applicable and no masking. There is no concurrent control group, so a treatment contrast cannot be estimated from the study design. A comparison with an external or historical group would require additional information and assumptions; such a comparison is not reported in the registry record.

The registry record lists 0 analyses. It does not report a statistical analysis plan, including methods for estimation, any adjustment for covariates, or procedures for handling multiple outcomes. The absence of a listed analysis does not mean no analyses were conducted outside the registry; it means the registry record does not document them. A prespecified analysis plan would ordinarily clarify how outcomes were summarized, how missing observations were treated, and which conclusions were confirmatory. Those details are not reported in the registry record.

The record lists 12 outcome measures. When a study evaluates multiple outcomes, multiplicity can matter if many statistical tests are used to support claims: the chance of at least one apparently notable result can increase as more tests are considered. A multiplicity adjustment is not automatically necessary for every descriptive outcome, but the analysis strategy should explain how outcomes are interpreted. The registry record does not report such a strategy. The outcome list alone does not show which results, if any, were treated as confirmatory.

The registry record defines the safety population as participants who received at least one dose. This is a treatment-exposed population, appropriate for describing observed safety experience under the stated definition. The record does not report the analysis population or missing-data approach for each secondary outcome. Missingness can affect interpretation when participants do not complete assessments or when measurements are unavailable. General methods may include analyses of available observations, imputation, or sensitivity analyses, but none of these approaches should be attributed to this study without documentation.

The sample-size assumptions recorded for a planning illustration are not a report of the trial's own design justification. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Those assumptions describe a hypothetical planning exercise, not this single-group study's allocation or an observed-power calculation. Sample-size illustrations are planning quantities; they do not establish the probability that a completed study detected an effect. The registry record does not report a sample-size justification for the trial itself.

Finally, a pharmacokinetic outcome such as a concentration or area under a concentration-time curve describes drug exposure, while an antibody outcome concerns the detection of antibodies against RVT-1401. Proptosis outcomes describe changes in an eye measurement or a response classification. These are different outcome types and require their own definitions and analysis details. Their names are registered, but numerical results and analysis methods for them are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures, including the primary safety outcome and secondary outcomes concerning proptosis, RVT-1401 exposure, and anti-RVT-1401 antibodies. Evaluating several outcomes can create multiplicity concerns when multiple statistical tests are used to support confirmatory conclusions. In general, an analysis plan should clarify which outcomes are primary, how secondary outcomes are interpreted, and whether any multiplicity adjustment is intended. A multiplicity procedure is not reported in the registry record.

The record lists 0 analyses and does not report a statistical analysis plan. Consequently, details such as the tests or estimation methods used, any covariate adjustment, and the treatment of repeated measurements are not reported in the registry record. The registered outcome list alone does not establish which findings were confirmatory or how results were selected for interpretation.

The primary outcome defines the safety population as participants who received at least one dose of study treatment. The adverse-event figures give 7 participants at risk in the RVT-1401 group. For the secondary outcomes, the registry record does not describe analysis populations or the handling of unavailable measurements. Missingness, reasons for missing data, and any imputation or sensitivity analyses are not reported in the registry record.

Missing-data methods matter because an analysis based only on observed measurements may not represent participants with unavailable outcomes if their missingness is related to their health status or response. Imputation and sensitivity analyses can address some uncertainties, but their appropriateness depends on the outcome and the reasons data are missing. No particular approach can be attributed to this study from the registry record.

The record also does not report a sample-size justification. The planning assumptions associated with a sample-size illustration do not establish the trial's design rationale, and planning calculations are not observed power. With no analysis plan or missing-data details reported, interpretation should remain tied to the descriptive information available for the safety 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports 7 participants at risk in the RVT-1401 group, 0 participants with serious adverse events, and 0 deaths. It also reports 7 participants with other adverse events. These are participant counts, not counts of every event occurrence, and they do not provide event duration or severity grading for the other events.

A zero serious-event count means that no serious adverse events are recorded in this group during the stated observation period. It does not show that serious events are impossible, nor does it establish a zero underlying risk. The study enrolled 7 participants, so the observed safety experience is limited to the small group and the specified treatment period. No comparison group is available to show whether the observed counts differ from another treatment or from background event rates.

Seriousness and treatment relationship should be read separately. The record defines serious events by their consequences or medical importance. It does not report a separate count for treatment-related adverse events. The count of other adverse events should not be interpreted as the treatment-related count, and the registry record does not provide enough detail to determine the relatedness of each event.

The primary endpoint timeframe is from baseline up to Week 6. The registry record does not report the specific serious-event terms or additional participant-level details. These figures therefore summarize recorded safety counts, not a complete characterization of each event or a comparative assessment of risk.

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

The result describes the safety experience recorded among participants receiving RVT-1401 in this single-group study. The registry record reports 7 participants with other adverse events, 0 with serious adverse events, and 0 deaths in the RVT-1401 group. These counts are relevant to the study's safety objective, but they are not a controlled estimate of treatment effect. The record does not report a separate count for treatment-related adverse events.

The findings do not establish that RVT-1401 caused the recorded events. The adverse-event definition includes events whether or not they are considered related to the medicinal product, and the registry record does not provide event-by-event relatedness information. Likewise, the absence of serious adverse events or deaths in the recorded group does not establish that such outcomes cannot occur. A study with a small group can describe observed experience, but uncommon outcomes may not be observed.

The single-group, open-label design also limits comparisons. Without a concurrent control condition, changes during the study cannot be distinguished from changes that might have occurred over time or for other reasons. The study does not provide a randomized comparison of safety or efficacy. The record's secondary outcome titles identify proptosis, drug exposure, and antibody outcomes, but their numerical results are not reported in the registry record. No treatment benefit should be inferred from the outcome list or from the safety counts.

The study's purpose included evaluating safety, tolerability, and pharmacodynamic parameters. The posted safety counts speak only to the adverse-event information recorded for the primary endpoint. They do not by themselves summarize tolerability in all its aspects or establish pharmacodynamic effects. Detailed participant characteristics, missing-data handling, statistical analyses, and a sample-size justification are not reported in the registry record.

In general, a clinical trial result is interpreted in light of the endpoint definitions, observation period, study design, precision, and completeness of reporting. Here, the record supports a descriptive statement about recorded events during treatment, but not a causal conclusion, a comparative claim, or a precise estimate of risk beyond the study group. Further results and methodological details are not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why design and endpoint interpretation matter even when the main outcome is a straightforward count. The registry record presents safety outcomes for RVT-1401 in a single-group, open-label study. Counts can communicate what was observed among treated participants, but a count alone does not provide a comparison with another treatment or with an untreated course of disease. The absence of randomization and a concurrent control group limits causal interpretation.

The endpoint also combines categories that should not be conflated. Treatment-emergent status depends on event timing, seriousness depends on the event's consequences or medical importance, and treatment-relatedness is a separate judgment. Reporting each component separately helps readers distinguish these concepts. The registry record does not provide a separate treatment-related event count, so the other-event figure cannot stand in for that result.

Precision is another central statistical issue. The record reports enrollment of 7 and a safety risk count of 7. Such a group can contribute descriptive observations, but a zero count does not quantify how likely an event would be in a broader population. Confidence intervals and a clear analysis plan would help characterize uncertainty; neither is reported in the registry record for these safety figures.

The study also registered clinical and pharmacologic outcomes beyond adverse events. Their presence underscores that a trial can address several kinds of questions, each requiring clear definitions, populations, and analysis methods. The registry record lists 12 outcome measures and 0 analyses, so it does not document how multiplicity or missing outcome data were handled.

Statistically, the record is useful for distinguishing observed safety counts from comparative evidence. It shows what was recorded in this study group, while leaving important questions about precision, relatedness, missingness, and other outcomes unreported. This distinction is essential when describing early-phase, single-group trial evidence without overstating what the design can answer.

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 design limitation is the absence of a concurrent comparison group. Because the study is single-group and open-label, the observed outcomes cannot be contrasted with outcomes under another treatment or without treatment within the trial. This restricts causal interpretation and makes it difficult to separate treatment-associated observations from background variation or time-related changes.

The enrolled group was 7 participants. The safety figures therefore describe a limited study experience, and uncommon events may not be observed. The registry record does not report confidence intervals for the safety counts, so their precision as estimates for a broader population is not quantified. The record also does not provide the specific terms for serious events; the reported serious-event and death counts are 0.

The primary endpoint names several safety components, but the record does not separately report every component count. In particular, a distinct count of treatment-related adverse events is not reported in the registry record. Details about the other adverse events, such as event terms, severity grading, duration, and participant-level timing, are not reported in the registry record.

Important participant and conduct details are also not reported in the registry record. These include further eligibility criteria, baseline characteristics, adherence, treatment discontinuations, and reasons for missing assessments. Missing-data methods, the statistical analysis plan, multiplicity handling, and a trial-specific sample-size justification are not reported in the registry record. The secondary outcome titles are listed, but their numerical results and analyses are not reported in the registry record.

These reporting gaps mean that interpretation must remain focused on the available descriptive safety counts and the stated design. They do not support claims about comparative effects, causal relationships, or outcomes beyond those explicitly reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy (GO) — NCT03922321.
• Registry record last updated 2022-01-24; status last verified 2021-12.
• Results first posted 2022-01-24.
• 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.

18. Record Summary

The registry record describes a completed Phase 2a, multicenter, open-label, single-group study of subcutaneous RVT-1401 in participants with moderate to severe active Graves' Ophthalmopathy. Enrollment was 7. The listed regimen was 680 mg weekly for two weeks followed by 340 mg weekly for four weeks. The study began on 2019-04-22 and had a primary completion date of 2020-02-29.

The primary endpoint counted participants with treatment-emergent adverse events, serious adverse events, treatment-related adverse events, and deaths during the 6-week treatment period. The record reports 7 participants with other adverse events, 0 with serious adverse events, and 0 deaths. A separate treatment-related event count is not reported in the registry record.

Secondary outcomes included proptosis, RVT-1401 exposure, and anti-RVT-1401 antibodies. Their numerical results, the analysis plan, missing-data handling, multiplicity procedures, and a trial-specific sample-size justification are not reported in the registry record. The single-group design supports descriptive reporting, not a randomized treatment comparison.