Phase 1/2a Clinical Trial to Assess the Safety of HB-adMSCs for the Treatment of Rheumatoid Arthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1/2a Clinical Trial to Assess the Safety of HB-adMSCs for the Treatment of Rheumatoid Arthritis (NCT03691909), a na phase 1, phase 2 study. The primary outcome is Total Number of Adverse Events and Serious Adverse Events.

2. Clinical Question

The study also listed outcomes concerning TNF-a, IL-6, CRP, ESR, and joint count. Those measures address biological markers and joint assessment alongside the safety focus. Their presence does not create a randomized comparison: all participants were assigned to the same treatment arm, and no untreated or active-control group is described.

The question should therefore be read as a descriptive safety question about outcomes observed after treatment, not as an estimate of how HB-adMSCs compare with another intervention. The registry record does not establish whether any change in an outcome was caused by treatment. It also does not report a comparative treatment effect for the listed secondary outcomes.

3. Trial Design

This completed Phase 1/2a study evaluated HB-adMSCs in adults with active rheumatoid arthritis. The registry describes a single-group, open-label design: allocation is listed as not applicable, masking as none, and one treatment arm is described. The listed enrollment is 15. The study began on 2018-09-25, and primary completion is recorded as 2020-08-17.

The intervention was a single intravenous administration of autologous adipose-derived mesenchymal stem cells. The arm description states that laboratory data would be collected before infusion and compared with follow-up data at 1, 3, 6, and 12 months. Joint Assessment 68 was also scheduled at 1, 3, 6, and 12 months. These descriptions indicate planned observation over time, but the registry record does not report results for those assessment time points in the registry record for this analysis.

The primary outcome is the total number of adverse events and serious adverse events across participants over 12 months. Its stated population is participants who received treatment and completed at least 5 of 7 follow-up assessments. The adverse-event summary separately lists 15 participants at risk in the treatment arm. The record does not explain whether or how these population descriptions correspond to one another.

Because the trial has no control arm, its design can describe events observed in the treated group but cannot directly compare event frequency with an alternative treatment or no treatment. Comparing follow-up with baseline, as planned in the arm description, is also not equivalent to a randomized comparison: changes over time may reflect factors other than the infusion. The registry record does not report a detailed statistical analysis plan, sample-size justification, or further design rationale.

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: Of 23 screened participants, 15 met inclusion criteria, were enrolled, and given treatment.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants who received treatment and completed at least 5 of 7 follow up assessments.

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 Total Number of Adverse Events and Serious Adverse Events, measured over 12 months.

The primary endpoint is the total number of adverse events and serious adverse events across participants over 12 months. It is recorded as a count of events. The stated population consists of participants who received treatment and completed at least 5 of 7 follow-up assessments.

An event count describes how many events were recorded across the group; it is not the same quantity as the number of participants who experienced at least one event. In general, one participant may experience more than one event, so an event total can reflect repeated events in the same person. A participant-level count instead indicates how many people experienced an event, without describing the full number of events. The registry’s adverse-event summary reports participant counts affected, while the primary endpoint description specifies a total event count.

Counting adverse events is useful in a safety-focused study because it provides a direct summary of reported events during follow-up. Serious adverse events are distinguished from other adverse events, allowing the record to convey event seriousness as well as overall event reporting. However, counts alone do not describe event duration, severity beyond the serious classification, timing, relatedness to treatment, or clinical context unless those details are separately reported.

The primary endpoint’s total event count is not reported in the registry record. The participant counts in the adverse-event summary should not be substituted for it: they answer a different descriptive question. Without the total count and further detail on events, the primary endpoint cannot be interpreted as a complete measure of event burden.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a count endpoint and a single-group design, but does not report the statistical methods used to analyze the primary outcome. The following concepts explain how such data are generally interpreted; they are not claims about methods used by this trial.

What does a count endpoint describe?

A count endpoint records the number of events rather than a continuous measurement or a yes-or-no outcome for each participant. For an event-count analysis, the unit being counted matters. A total across participants can include multiple events in one person, while a count of affected participants records whether people experienced at least one event. Those quantities answer different questions. Here, the primary endpoint is described as a total number of events, whereas the posted adverse-event summary gives numbers of participants affected. The total event count itself is not reported in the registry record.

Count data are often nonnegative and can be unevenly distributed: many participants may have few recorded events while some have several. A simple model may assume that the variation in counts follows a particular relationship with the average count. If real data vary more than that model expects, the data are over-dispersed. In general, allowing for over-dispersion can produce more appropriate uncertainty estimates; ignoring it can make estimates appear more precise than they are. The registry record does not identify a count model, report a dispersion assessment, or state whether any model was used.

How would uncertainty be expressed?

A confidence interval is a statistical range that conveys uncertainty around an estimate under the assumptions of the analysis. For counts, an interval might accompany an estimated event rate or a difference between groups, depending on the question and method. A narrow interval indicates greater precision under those assumptions; a wide interval indicates greater uncertainty. An interval does not by itself establish causation or remove bias from study design. No confidence interval for the primary endpoint is reported in the registry record, and no interval can be inferred from the participant counts alone.

A p-value, when used, describes how compatible the observed data are with a specified statistical model or null hypothesis. It is not a measure of the size or clinical importance of an effect. The registry record does not report a p-value or a primary-outcome hypothesis test. With no comparator arm identified, a between-group treatment contrast is not available from this design.

What does the single-group design allow?

In a single-group study, outcome counts can describe what was observed among treated participants. They do not directly estimate a contrast against an untreated group or another treatment. A before-and-after comparison, when performed, uses participants’ earlier measurements as a reference, but it does not provide the same protection against confounding as randomized allocation to a concurrent comparison group. The arm description says laboratory data would be compared with baseline at follow-up, but the registry record does not report the analysis used for those comparisons or their results in the information available for this interpretation.

Masking is listed as none. In general, masking can reduce the influence of knowledge about treatment assignment on assessment or reporting, where feasible. The registry record does not describe any masking procedures. Nor does it state how adverse events were collected, assessed for seriousness, or judged for possible relationship to treatment. Such details are important to interpret safety counts, but they are not reported in the registry record.

What do the planning assumptions mean?

The sample-size planning illustration is not the trial’s own design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes planning to detect a stated fraction of the observed effect. These are hypothetical planning assumptions, not evidence that the trial enrolled two arms or used that allocation: the actual design is recorded as single-group, with allocation not applicable.

Such illustrations are conditional on their assumptions and on an effect estimate used as their reference. They are not observed power, do not show that a study was adequately powered, and do not replace a prespecified sample-size calculation. The registry record does not report the trial’s own sample-size justification or statistical plan. It also does not report the primary endpoint total needed to interpret an observed event-count effect from this record. Accordingly, the illustration cannot establish the precision or inferential strength of the trial’s safety findings.

These methodological distinctions matter because event totals, participant counts, and comparative estimates are not interchangeable. The registry gives some participant-level safety counts, but not the primary event total or an inferential analysis. The most defensible interpretation is therefore descriptive and limited to the quantities explicitly reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry records 6 outcome measures and 6 analyses. Secondary outcomes listed in the record concern TNF-a, IL-6, CRP, ESR, and joint count. The primary outcome concerns total adverse events and serious adverse events. Multiple outcomes create the general possibility of multiplicity: when many hypotheses are examined, the chance of at least one apparently notable result can increase. Statistical plans sometimes address this with a prespecified hierarchy or adjustment, but the registry record does not report whether any such approach was used. It does not report which outcomes were treated as confirmatory or exploratory, or how results across outcomes were interpreted together.

The record describes the primary endpoint population as participants who received treatment and completed at least 5 of 7 follow-up assessments. It does not report how many participants met that definition, whether all participants had complete endpoint data, or how missing assessments were handled. There is no reported imputation method, sensitivity analysis, or explanation of the effect of missing data on the endpoint. Because the primary event total is also not reported, the endpoint cannot be independently assessed from the registry information.

The adverse-event summary separately lists 15 participants at risk in the treatment arm. The record does not explain how that risk set relates to the primary endpoint population defined by follow-up completion. No assumption should be made that the two descriptions use identical inclusion rules. The record also does not state whether analyses followed an intention-to-treat principle, a treated-participant principle, or another analysis-population definition beyond the primary endpoint description. These omissions limit assessment of completeness, selection, and multiplicity.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: skin infection (6.7%), intestinal resection (6.7%), intestinal obstruction (6.7%), abdominal pain (6.7%), urinary tract infection (6.7%).

The treatment-arm safety summary reports 4 participants affected by serious adverse events among 15 at risk, 14 participants affected by other adverse events among 15 at risk, and 0 deaths. These figures describe participants affected, not the total number of events. They should not be treated as interchangeable with the primary endpoint, which is specified as a total event count over 12 months and is not reported in the registry record.

The serious adverse event terms listed are skin infection, intestinal resection, intestinal obstruction, abdominal pain, and urinary tract infection. Each term is reported at 6.7%. The registry does not give event-level descriptions or explain the relation of each listed term to individual participants, so the terms and percentages do not establish a complete count of events or their timing. The record also does not report whether events were judged related to the infusion.

In general, a serious adverse event classification concerns seriousness, while an adverse event is a broader reporting category; neither label alone establishes causation. With no comparison group, these figures describe what was recorded in the treated group and do not quantify excess risk attributable to treatment.

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

The results give a limited descriptive account of safety reporting in the treatment arm: 4 participants were affected by serious adverse events, 14 by other adverse events, and 0 deaths were reported. The serious adverse event list includes five named terms, each reported at 6.7%. These findings describe the registry entries; they do not provide a full account of event burden because the primary endpoint’s total number of events is not reported.

The record does not show whether events were caused by HB-adMSCs. A single-group study has no concurrent control group to distinguish treatment-associated events from events that might occur in the underlying population or over time for other reasons. The registry’s plan to compare follow-up assessments with baseline can describe within-participant change, but without reported results it cannot answer whether changes occurred. Even when such changes are available, a before-and-after comparison alone is not a randomized treatment contrast.

The findings also do not provide an estimate of comparative effectiveness. The secondary outcomes name inflammatory markers and joint count, but their results are not reported in the registry information available for this interpretation. No treatment effect estimate, confidence interval, or p-value for the primary outcome is reported. Consequently, the record does not quantify the precision of an effect or support a conclusion about how outcomes differ from another treatment.

These limits do not make the reported counts meaningless: they identify events recorded in the treatment group and describe the scope of the registry’s safety summary. They do mean that the counts should be interpreted in the context of the endpoint definition, incomplete event-total reporting, and noncomparative design. The registry status of completed describes trial status, not completeness of the statistical evidence presented.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why the outcome definition and the reported summary must be read together. Its primary endpoint is a total count of adverse events and serious adverse events, while the registry’s safety summary reports participants affected. Event totals and affected-participant counts answer different questions. A person-level count can indicate how many people had an event, but it does not show the number of repeated events or the distribution of events across participants. Since the total event count is not reported, the main endpoint cannot be evaluated directly from the posted safety figures.

The study also illustrates a core limitation of single-group evidence. A treatment-arm count can describe observed experience, but it has no concurrent control against which to estimate a comparative difference. That distinction matters for causal interpretation: timing after an infusion does not, by itself, establish that the infusion caused an event. The same issue applies to changes from baseline, which may be descriptive but cannot isolate treatment effects from other changes over time.

Finally, the record highlights the importance of transparent reporting of analysis populations, missing-data handling, and statistical methods. The primary outcome’s population is defined by treatment receipt and follow-up completion, but the record does not explain how that population relates to the adverse-event risk count. It does not describe missing-data methods or an analysis plan. These details affect how precisely readers can understand the reported safety data and how far they can generalize beyond the recorded participants. A completed status does not resolve these interpretive questions.

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 registry record has important limitations specific to interpreting this study. The primary endpoint is defined as the total number of adverse events and serious adverse events across participants over 12 months, but that event total is not reported. The safety summary instead gives counts of participants affected. Those figures cannot be used to reconstruct the primary endpoint, because the registry does not state how many events each participant experienced.

The study has a single treatment arm and no comparator. Thus, the reported event counts cannot be compared directly with an untreated group or another intervention, and they do not establish treatment causality. The absence of masking is recorded, but the registry does not explain event collection procedures or how seriousness and treatment relationship were assessed. The listed serious adverse event terms and percentages do not supply those missing details.

The primary endpoint population is defined by treatment receipt and completion of at least 5 of 7 follow-up assessments, while the adverse-event summary lists a risk count of 15. The record does not reconcile these definitions or report how missing assessments were handled. It also does not report an analysis plan, sample-size justification, multiplicity approach, or endpoint uncertainty estimates. The secondary outcomes are named, but their results are not present in the registry information available for this interpretation.

Finally, the planned baseline and follow-up comparisons are described, but the record does not report their results. Without those results and further methodological detail, neither changes over time nor the precision of the safety estimates can be assessed fully.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 1/2a Clinical Trial to Assess the Safety of HB-adMSCs for the Treatment of Rheumatoid Arthritis — NCT03691909.
• Registry record last updated 2025-09-26; status last verified 2025-09.
• Results first posted 2022-03-22.
• 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 describes a completed Phase 1/2a, single-group, open-label study of a single intravenous infusion of autologous adipose-derived mesenchymal stem cells in adults with active rheumatoid arthritis. Enrollment is listed as 15. The primary endpoint is the total number of adverse events and serious adverse events over 12 months among participants who received treatment and completed at least 5 of 7 follow-up assessments.

The treatment-arm safety summary reports 4 participants affected by serious adverse events, 14 affected by other adverse events, and 0 deaths, with 15 at risk. The primary endpoint’s total event count is not reported in the registry record. With no comparator arm, these figures are descriptive and do not establish a comparative treatment effect or causation. The registry does not report the statistical plan, missing-data methods, or results for the listed secondary outcomes.