An Open-Label Study of Intra-articular AMB-05X Injections in Subjects With Tenosynovial Giant Cell Tumor of the Knee: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Study of Intra-articular AMB-05X Injections in Subjects With Tenosynovial Giant Cell Tumor of the Knee (NCT04731675), a na phase 2 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events.

2. Clinical Question

This is principally a safety and tolerability question in the record’s stated primary outcome. The endpoint counts participants with treatment-emergent adverse events; it does not, by itself, establish whether an event was caused by treatment. Without a concurrent control group, the study cannot make a like-for-like comparison against a group that did not receive AMB-05X. The high-dose and low-dose safety listings are descriptive groups, not evidence of a randomized comparison.

The study also lists tumor response and measures of function, stiffness, pain and health assessment among its secondary outcomes. Those listed outcomes indicate areas the study intended to assess, but the registry record contains no analyses for them. Therefore, the central question that can be addressed from the posted results is limited to the displayed safety counts. Efficacy, changes from baseline and comparative effects are not established by those counts.

3. Trial Design

This is a Phase 2, multicenter, adaptive, open-label study of intra-articular AMB-05X in participants with tenosynovial giant cell tumor of the knee. The registry record lists a single-group model, allocation as not applicable and no masking. It records enrollment of 11 participants and a completed study status. The recorded study start was 2021-05-25, and the primary completion date was 2022-05-05.

The treatment description states that participants received an intra-articular injection once every 2 weeks for 12 weeks, for 6 treatments total. The intervention is identified as AMB-05X. Safety outcomes are presented for an AMB-05X high-dose group and an AMB-05X low-dose group. However, the registry record does not describe how the dose groups were assigned, whether dose groups were enrolled in a particular sequence, or what adaptive features were used. It also does not provide further details about the doses.

Open-label means masking was absent: participants and study personnel were not kept unaware of the assigned treatment. With no concurrent control group listed, the design does not offer a randomized, like-for-like control comparison. The two dose-group listings should therefore be read as descriptive safety summaries; the registry record does not establish them as randomized arms.

The primary outcome is the number of participants with treatment-emergent adverse events, with a 24-week timeframe and a stated population of all enrolled participants. The registry record also lists secondary outcomes concerning tumor response, range of motion, patient-reported physical function, stiffness, pain interference and health assessment. Although the study is described as adaptive, the specific adaptation rules, stopping criteria and decision process are not reported in the registry record. The statistical analysis plan and sample-size justification 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All enrolled pts

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.

Population: Subjects with TGCT of the knee

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events, measured over 24 weeks.

The primary endpoint counts participants with treatment-emergent adverse events. Its stated timeframe is 24 weeks, and its population is all enrolled participants. The endpoint description says that it concerns the frequency and severity of reported treatment-emergent adverse events. The posted safety results distinguish serious adverse events from other adverse events, but do not give a full event-by-event account or a severity breakdown.

In general, adverse-event endpoints are used to describe the types and extent of harms observed during a study. Counting participants rather than events gives a participant-level summary: a participant is counted as having an event, while the count alone does not indicate how many events that participant experienced. Such a summary is useful for safety monitoring, but it does not establish that treatment caused an event. Events can occur during a study for reasons unrelated to treatment, and a control group would be needed for a more direct comparative assessment of event frequency.

The registry record reports group-level counts for serious and other adverse events. It does not provide a complete primary-endpoint result with detailed event frequency and severity for all enrolled participants. Nor does it report an inferential analysis, such as an estimate with a confidence interval. The endpoint therefore provides descriptive safety information, with limited precision and no comparative causal interpretation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several design and statistical ideas help frame the registry results. The main distinction is between describing observed counts and estimating a treatment effect. The posted safety figures are descriptive: they report how many participants in each listed dose group were affected. A treatment effect would require a comparison that can distinguish treatment-related changes from other explanations. Because this study is listed as single-group, open-label and without masking, and no concurrent control group is described, the safety counts do not provide that kind of controlled estimate.

What does a participant count represent?

A participant-level adverse-event count records whether each participant experienced at least one event in the category being summarized. It does not count every event. A participant with more than one event may still contribute only once to a count of participants affected. Event counts, participant counts and event rates answer different questions; the registry’s safety groups identify participants at risk and participants affected. The record does not report the number of individual events, their timing, or a detailed account by event term.

The distinction between serious adverse events and other adverse events is also important. The serious-event listing reports participants at risk, participants affected and deaths. The other-event listing reports participants at risk and participants affected. These categories should not be conflated: a count of other adverse events is not a count of serious adverse events, and neither category alone provides a complete description of severity. The registry record does not list top serious-event terms and does not give a full severity distribution.

Why does the design affect interpretation?

A randomized controlled trial assigns participants to groups by a specified random process, supporting a balanced comparison on average. This record does not describe a randomized comparison; allocation is listed as not applicable, and the study model is single-group. Although safety counts appear under high-dose and low-dose group labels, the registry record does not explain the assignment process. It would therefore be inappropriate to treat those groups as if randomization had made them comparable.

Open-label means masking is absent. In general, knowledge of treatment can influence reporting, assessment and decisions about whether an event has occurred or how it is classified. This is a general methodological concern, not evidence that any particular posted count was biased. The registry record does not report procedures intended to assess or address such effects.

The study is described as adaptive, but that label alone does not identify how the design changed during conduct. Adaptive designs can use prespecified rules to modify aspects of a study as information accumulates. The rules, timing, decision criteria and any changes made in this study are not reported in the registry record. It is therefore not possible to assess from the record whether adaptation affected enrollment, dose groups, follow-up or analysis.

How should uncertainty be understood?

A confidence interval is a range of values compatible with the data under a stated statistical method. In general, it helps show the precision of an estimate: a narrow interval indicates greater precision than a wide interval. The registry record does not report confidence intervals for the safety counts. The counts can still be described directly, but without an interval or a stated model, their precision cannot be evaluated from the record in the same way as a modeled estimate.

Small groups generally yield imprecise estimates because each participant has substantial influence on the result. This is a general statistical point, not a new calculation for this study. A zero count is particularly easy to overinterpret: it means no event was recorded in the observed group, not that the underlying event risk is zero. The record does not report an inferential analysis to quantify uncertainty around the zero counts.

Adverse events can also be clustered within participants. If some participants experience multiple events, treating every event as independent can understate uncertainty. In general, over-dispersion occurs when the variation in event counts is greater than a simple statistical model expects; methods that account for that extra variation may be appropriate for event-count analyses. The posted results are participant counts, not a detailed event-count dataset, and the registry record does not report a model or an adjustment for over-dispersion.

What do planning illustrations mean?

Sample-size planning calculations are prospective illustrations of how many participants might be needed under chosen assumptions. They are not observed study outcomes and do not describe the actual precision of the posted results. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. They define the effect to detect as a stated fraction of the observed effect. These assumptions are not identified as the trial’s own design plan, and the registry record does not report its sample-size justification.

In general, a planning illustration depends on its assumptions about the effect, variability, significance level, power and allocation. If the assumptions differ from the actual study or from a future study, the illustration may not predict that study’s performance. It should not be interpreted as observed power or as evidence that the study did or did not detect a treatment effect. The registry record does not report an inferential efficacy analysis or the details needed to assess one.

Finally, the existence of multiple outcomes raises questions about multiplicity. When many outcomes are tested, the chance of at least one apparently notable finding can increase unless the analysis plan addresses the issue. The record lists 16 outcome measures but no analyses, and does not report a multiplicity strategy. No claim about statistical significance or adjustment can therefore be made from the outcome listings.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("AMB-05X - High Dose", "AMB-05X Low Dose")
n      <- c(8, 3)
events <- c(7, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  AMB-05X - High Dose  8  7  87.5  47.3  99.7  52.9  97.8  51.8  97.2
ARM  AMB-05X Low Dose  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 16 outcome measures, including the primary adverse-event outcome and secondary measures of tumor response, range of motion, physical function, stiffness, pain interference and health assessment. It reports 0 analyses. The presence of several planned outcomes creates a general multiplicity concern: testing many outcomes can increase the chance of at least one apparently unusual finding. Whether that concern was addressed, and by what method, is not reported in the registry record. No conclusions about statistical significance or adjustment for multiple testing can be drawn.

The record does not report a detailed statistical analysis plan, including the planned estimands, statistical models, confidence intervals, hypothesis tests or any interim analyses. The study is described as adaptive, but the rules governing adaptation and any consequences for analysis are not reported in the registry record. The record also does not report a sample-size justification. Planning illustrations based on stated assumptions should not be read as the trial’s own design rationale or as observed power.

Missing-data methods are not reported in the registry record. The outcome population is described as all enrolled participants, but the record does not explain how missing assessments, withdrawals, incomplete follow-up or participants without evaluable outcome data were handled. The duration of follow-up for the primary outcome is stated as 24 weeks, but that does not establish that every participant completed that timeframe. The record does not describe imputation, sensitivity analyses or rules for including participants in particular analyses.

These omissions limit assessment of how outcomes were analyzed and how robust any estimates would be to missing information or analytic choices. Since no analyses are reported, there is no basis for evaluating the numerical results of an efficacy analysis or for determining whether analysis populations differed from all enrolled participants.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety listing reports serious adverse events separately for the AMB-05X high-dose and low-dose groups. In the high-dose group, 0 of 8 participants at risk had a serious adverse event; in the low-dose group, 0 of 3 participants at risk had one. Deaths are listed as 0 in each group. For other adverse events, 7 of 8 high-dose participants and 2 of 3 low-dose participants are listed as affected.

These are participant counts, not counts of all events. The serious-event figures indicate that no serious events were recorded in the listed groups; they do not show that such events could not occur or provide a precise estimate of their frequency beyond the observed participants. The record gives no top serious-event terms, and the other-event figures do not identify event types, event totals per participant or severity distributions.

The groups are descriptive, not a like-for-like randomized comparison. The registry record does not explain how participants were assigned to dose groups. Differences between the group counts should not be interpreted as evidence that one dose caused more or fewer events. The open-label, uncontrolled design also limits causal interpretation. The safety listing is useful as a record of observed counts, but it is not a substitute for a complete event-level safety analysis or a controlled estimate.

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

The posted results establish that the registry record contains safety counts for participants listed in AMB-05X high-dose and low-dose groups. It records no serious adverse events and no deaths in either group, while also recording participants with other adverse events. These are observations from this study, and they are appropriately read as descriptive counts within the listed groups.

They do not establish that AMB-05X caused or prevented any adverse event. There is no concurrent control group described, no masking, and no reported randomized comparison. The registry record does not explain how participants entered the high-dose and low-dose groups. Consequently, the counts cannot isolate a treatment effect or support a causal comparison between dose groups.

The results also do not establish the absence of risk. A zero count is an observation in the participants studied, not proof that an event cannot occur. The group sizes are limited, and the record does not report confidence intervals or another uncertainty analysis. Further, the record does not provide detailed event terms, severity distributions or event-level counts for the safety results.

The study’s listed secondary outcomes include tumor response, physical function, stiffness, pain and health assessment. The registry record reports no analyses for these outcomes. The safety counts therefore do not show whether participants’ tumors, symptoms or function changed. Nor do they demonstrate comparative efficacy, a dose-response relationship, or results beyond the population and follow-up described.

In general, a clinical study result is best interpreted in light of its design, outcome definitions, uncertainty and completeness of reporting. In this case, the available record supports a narrow description of posted safety counts. It does not support treatment recommendations or a conclusion about clinical benefit, and it does not supply enough analytical detail for a broader assessment of efficacy or risk.

14. Why This Trial Matters Statistically

This study matters statistically because it illustrates the difference between a safety description and a comparative treatment evaluation. The registry reports adverse-event counts from an open-label, single-group study, with results separated into high-dose and low-dose listings. Such counts can document what was observed in the enrolled participants, while the absence of a concurrent control limits what can be inferred about causes or comparative effects.

It also highlights how denominator size affects interpretation. A count of 0 serious adverse events is meaningful as a description of the participants observed, but it should not be mistaken for a precise estimate of the underlying risk. With a limited number of participants, the evidence remains uncertain, and the registry record does not report confidence intervals to quantify that uncertainty. The same caution applies to counts of other adverse events.

The design is called adaptive, yet the record does not explain its adaptation rules. That distinction matters: the word adaptive does not itself reveal whether decisions were prespecified, how information was used, or whether analysis was affected. A clear account of these features is important for interpreting both conduct and results.

Finally, the record lists multiple outcome measures but no analyses. This makes it impossible to assess the results of the listed efficacy and patient-reported outcomes, or to determine how multiplicity and missing data were handled. The statistical value of the record is therefore primarily descriptive: it helps identify what safety counts were posted and also makes visible the limits created by absent comparisons and analytic detail.

15. Limitations

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

The small enrollment limits the precision and breadth of the safety description. The group counts are based on 8 participants at risk in the high-dose group and 3 in the low-dose group. These observations cannot establish how often events would occur in a larger or different population. The registry record does not report confidence intervals or a model that would quantify uncertainty.

The study is open-label and has no concurrent control group listed. Participants and study personnel were not masked, and the record does not describe random assignment. Although the safety counts are separated by dose group, the process that placed participants in those groups is not reported in the registry record. The groups should not be treated as a controlled comparison.

Reporting is incomplete for interpreting safety in detail. The record does not provide event-level data, specific terms for the other adverse events, the number of events per participant, or a full breakdown by severity. It lists no top serious-event terms. The primary outcome describes frequency and severity over 24 weeks, but the posted counts do not provide that full detail.

The registry record lists secondary outcomes but no analyses. It does not report how missing data or withdrawals were handled, whether all participants completed follow-up, or how the adaptive design operated. Statistical methods, interim analyses, multiplicity handling and the sample-size justification are not reported in the registry record. These gaps prevent a fuller assessment of efficacy, uncertainty and analytic robustness.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open-Label Study of Intra-articular AMB-05X Injections in Subjects With Tenosynovial Giant Cell Tumor of the Knee — NCT04731675.
• Registry record last updated 2024-06-27; status last verified 2024-06.
• Results first posted 2024-06-27.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes NCT04731675, a completed Phase 2, multicenter, adaptive, open-label study of intra-articular AMB-05X in knee tenosynovial giant cell tumor. It lists 11 participants, a single-group model, no masking and no applicable allocation. The treatment description specifies injections once every 2 weeks for 12 weeks, for 6 treatments total.

The primary outcome is the number of participants with treatment-emergent adverse events over 24 weeks, among all enrolled participants. Posted safety counts are separated into high-dose and low-dose groups. Serious adverse events and deaths are listed as 0 in each group; participants with other adverse events are also reported.

The record lists 16 outcome measures and no analyses. It does not report a concurrent control comparison, an efficacy analysis, detailed statistical methods, missing-data handling or the adaptation rules. The available results therefore support descriptive interpretation of safety counts, not comparative or causal conclusions.