Safety & Tolerability Study of Chimeric Antigen Receptor T-Reg Cell Therapy in Living Donor Renal Transplant Recipients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety & Tolerability Study of Chimeric Antigen Receptor T-Reg Cell Therapy in Living Donor Renal Transplant Recipients (NCT04817774), a non-randomized phase 1, phase 2 study. The primary outcome is Short Term Safety and Tolerability of TX200-TR101 Infusion..

2. Clinical Question

3. Trial Design

The registry describes a multicentre, open-label, single ascending dose, dose-ranging Phase I/IIa study. Allocation was non-randomized, masking was absent, and the study model was sequential. These features describe an early clinical investigation organized around safety and tolerability rather than a randomized comparison designed to estimate a treatment effect. Enrollment was 26. The registry record lists the study as completed, with a start date of 2021-03-17 and primary completion on 2024-07-11.

Participants in the treatment group underwent kidney transplant according to planned standard of care and received TX200-TR101 after transplantation. The control group underwent transplant according to planned standard of care without study drug. The adverse-event record further separates treatment recipients into groups labelled DL1, DL2, DL3 and DL4. It also lists a control group and a donor group. The meaning of dose labels beyond their group labels is not reported in the registry record.

Because allocation was not randomized and the trial was open-label, treatment and control groups should not be read as exchangeable comparison groups. Sequential dose escalation can be useful for early safety evaluation, but group size and order can influence what is observed; the detailed escalation rules and timing are not reported in the registry record. The registry record does not report a protocol for controlling differences between treatment and control groups, nor a statistical analysis plan describing adjusted comparisons.

The safety analysis population is described differently for treated participants and controls: treated participants received a transplant and infusion, while controls remained in the study at week 12 post-transplant. Such population definitions matter because they determine which participants contribute to the reported endpoint. The detailed participant flow, including reasons for any exclusions or missing observations, is 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: There were 13 participants enrolled as well as 13 kidney donors whose completed after transplant therefore bringing the total protocol enrollment to 26.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set. All participants who received a kidney transplant and TX200-TR101 infusion or for controls transplant remained in the study at week 12 post-transplant.

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: Kidney transplant donors (who completed the study after transplantation) and kidney recipients who reached 12 weeks post-transplant visit.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Short Term Safety and Tolerability of TX200-TR101 Infusion., measured over 28 days post infusion.

The primary endpoint is short-term safety and tolerability of TX200-TR101. It measures the incidence and grade of treatment-emergent adverse events, including serious adverse events, according to CTCAE V5.0. The timeframe is 28 days post infusion, and the endpoint unit is participants. In practical terms, the endpoint is intended to describe how many participants experienced events and how those events were graded during the stated follow-up period.

Safety endpoints are important in early studies because they characterize harms and tolerability before the evidence base is large enough to support precise estimates. Counting participants with events is different from counting every event: a participant may experience more than one event, but the participant-level measure concerns whether a person experienced an event. The registry record includes affected-participant counts for serious and other adverse events by group. It does not report complete primary endpoint results by grade or an explicit numerical summary of the primary endpoint in the registry record.

The stated endpoint is not itself a measure of whether the therapy prevents rejection or improves graft outcomes. The registry lists graft-related outcomes among secondary outcomes, but their detailed results are not reported in the registry record. The safety findings should therefore be interpreted as descriptive observations in the listed groups and within the reported follow-up framework, not as evidence of comparative efficacy.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is expressed as participants with an event, a count-based outcome. A participant-level count is useful for describing how many people experienced an adverse event, but it does not capture every aspect of the event burden. It may not distinguish one event from repeated events in the same participant unless event-level results are reported separately. The registry’s primary endpoint description includes incidence and grade, but the adverse-event record gives affected-participant counts by group; full grade-specific primary endpoint results are not reported in the registry record.

In general, a confidence interval communicates uncertainty around an estimated quantity. For an event proportion, it can show a range of values compatible with the observed data under the statistical method used. Small groups generally produce less precise estimates than larger groups, and a zero observed count does not establish a zero underlying event probability. No confidence intervals are reported for the adverse-event counts in the registry record. Their absence means the precision of these group-specific estimates cannot be assessed from the posted results alone.

In general, a hypothesis test assesses how compatible observed data are with a specified statistical model or null hypothesis. A p-value is not the probability that a treatment works, and it does not measure the size or clinical importance of an effect. The registry record lists zero analyses for this outcome information and does not report p-values or a formal between-group test. In this setting, interpreting the counts descriptively is more appropriate than implying a statistical comparison that the record does not report.

Non-randomized allocation is important to interpretation. Randomization, when used, helps balance measured and unmeasured prognostic factors across groups on average. Without random allocation, a difference in event counts between treatment and control groups may reflect differences in who entered each group, when they were treated, or other features of care. An adjusted analysis can sometimes account for recorded covariates, but no such analysis is reported in the registry record. Even an adjusted result would depend on the variables measured and the model assumptions.

The sequential model and ascending dose-ranging description indicate a design organized into successive treatment groups. Such a structure can support staged safety observation, but interpretation depends on the actual escalation rules, cohort review procedures, stopping criteria and follow-up. These details, including any planned interim analyses, are not reported in the registry record. The group labels DL1 through DL4 identify the listed cohorts; specific dose amounts and the rationale for choosing them are not reported in the registry record.

The record states that adverse events are graded according to CTCAE V5.0. In general, a grading system provides standardized categories for describing event severity. Standardization can aid consistent recording, but the clinical meaning of a grade still depends on the event and context. The listed group counts do not provide a grade-by-grade breakdown, and the registry record does not report the complete distribution of grades for this endpoint.

Sample-size planning illustrations are distinct from the trial’s actual enrollment and from observed power. The registry’s stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of the observed effect. The stated planning approach is not the trial’s own design. For time-to-event outcomes, the stated convention is total events; for other outcomes, it is participants per arm. Those assumptions do not establish the trial’s original sample-size justification, and that justification is not reported in the registry record. A planning illustration cannot show that the completed study had adequate power for its endpoint.

For event-count outcomes, the analysis population and observation period define what the count means. The primary safety set includes treated participants who received both transplant and infusion, while controls are described as transplant participants who remained in the study at week 12 post-transplant. The primary endpoint timeframe is 28 days post infusion. The adverse-event record supplies group-level at-risk counts, but the registry record does not detail event onset timing, exposure time, treatment discontinuations, or how missing safety observations were handled. Those omissions limit interpretation of completeness and comparability.

Statistical interpretation therefore rests on separating three things: what was observed, how uncertain the estimate is, and whether a causal comparison is supported. The registry lists observed counts, but does not report uncertainty intervals or inferential analyses. The design does not support treating the treatment and control groups as randomized counterparts. The posted evidence is best read as descriptive safety information from the listed participants and groups.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy, such as a hierarchy of outcomes, an adjustment across multiple tests, or a rule for interpreting several comparisons together. It lists seven outcome measures and several secondary outcome categories, including acute and chronic graft-related outcomes, long-term safety, immunosuppression and graft localization. The detailed results for these outcomes are not reported in the registry record. Without a stated analysis plan, it is not possible to determine which outcomes were prioritized for formal testing or how any multiplicity was addressed.

The registry record lists zero analyses. It does not report a statistical analysis plan, hypothesis tests, confidence intervals, or adjustments for covariates for the adverse-event counts. This should be understood as a lack of analyses listed in the record, not as proof that no analysis was conducted outside it. The original sample-size rationale, any interim analysis plan, and any stopping rules are also not reported in the registry record.

Missing-data handling is not reported in the registry record. The record defines the safety analysis set, but does not describe missing event assessments, withdrawals, incomplete follow-up, or how those situations were handled. It also does not report sensitivity analyses for alternative assumptions about missing observations. These omissions matter because safety summaries depend on the extent and timing of observation, and participants with incomplete follow-up may have fewer opportunities for events to be recorded.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: blood creatinine increased (100.0%), catheter site haemorrhage (33.3%), ureteric obstruction (33.3%), lymphocele (33.3%), gastroenteritis (25.0%).

The serious adverse-event counts are listed by group, with the number at risk and the number affected. They are 2 of 4 in DL1, 0 of 1 in DL2, 1 of 1 in DL3, 2 of 3 in DL4, 2 of 4 controls, and 0 of 13 donors. These are participant counts in the registry record, not estimates adjusted for differences between groups. Because the study was non-randomized, the counts should not be read as a direct treatment-versus-control effect.

The registry also lists serious event terms with percentages: “Blood creatinine increased” at 100.0%, “Catheter site haemorrhage,” “Ureteric obstruction” and “Lymphocele” at 33.3% each, and “Gastroenteritis” and “Pyelonephritis” at 25.0% each. The denominator and counting convention for these term-level percentages are not reported in the registry record. They should therefore be interpreted as the percentages attached to the listed terms, not converted into additional participant counts.

In general, serious adverse events are distinct from all adverse events, and the same participant may experience multiple events. The counts alone do not explain event timing, duration, attribution, outcome, or grade. These details are not reported in the registry record. A zero count means no affected participant is listed for that group; it does not establish that serious events cannot occur.

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

The results support a descriptive account of adverse events among participants listed in this early, non-randomized study. The record shows that serious adverse events were reported in several treatment groups and in the control group, while none are listed for the donor group. Other adverse events are listed for the treatment and control groups, and none for donors. These observations describe the participants in the registry record; they do not establish the comparative safety of TX200-TR101.

The design is not randomized, and the groups are small and uneven in size. Consequently, raw count differences cannot be attributed to the intervention without strong assumptions that the registry record does not establish. The data also do not show whether event patterns differ by dose in a reliable way. Some cohorts have only 1 participant, making their counts particularly limited as a basis for generalization. The registry record does not report confidence intervals or inferential comparisons that would quantify uncertainty or test group differences.

The primary endpoint concerns treatment-emergent adverse events during 28 days post infusion, including event grade under CTCAE V5.0. The posted group counts do not provide a full grade-specific account, and the record does not give a complete numerical summary of all aspects of the primary endpoint. The term-level percentages also have no reported denominator convention. Therefore, the counts should not be treated as a complete assessment of adverse-event severity or frequency.

The findings do not establish that TX200-TR101 prevents rejection, improves graft outcomes, changes immunosuppression needs, or affects long-term safety. Although the registry lists related secondary outcomes, their detailed results are not reported in the registry record. The short-term safety endpoint and descriptive adverse-event counts cannot answer those distinct questions.

In general, early dose-ranging studies can contribute information about tolerability and inform further study, but their results are typically limited by small cohorts and the design used. The record does not report enough detail about missing observations, event attribution, follow-up completeness, or analysis methods to resolve those uncertainties. The appropriate interpretation is bounded: the record documents adverse events among listed participants, while the size, precision and causal meaning of any treatment-related differences remain uncertain.

13. Why This Trial Matters Statistically

This study is statistically notable because it combines a sequential, dose-ranging approach with a safety endpoint in a setting where treatment and control groups were not randomized. Those design features determine what can be learned from the data. The adverse-event counts can describe what was recorded in each listed group, but they do not by themselves provide a reliable causal estimate comparing treatment with control.

The small group sizes make precision a central concern. In particular, groups with only 1 participant cannot provide stable estimates of event frequency. A count is useful for transparent reporting, but an estimate of underlying risk requires uncertainty to be considered. The registry record does not report confidence intervals or formal statistical analyses, so readers cannot assess the precision of a comparative effect from the record.

The endpoint also illustrates why analysis populations and timeframes matter. The primary safety set is defined around receiving transplant and infusion for treated participants, and remaining in the study at week 12 post-transplant for controls. The primary endpoint timeframe is 28 days post infusion. Differences in eligibility for the analysis set or completeness of follow-up can affect the meaning of group summaries, while details about missing observations are not reported.

Finally, the record distinguishes serious from other adverse events and lists specific serious event terms. Keeping participant counts, event terms and percentages conceptually separate prevents overinterpretation. The denominator for the term-level percentages is not reported, and multiple events may not correspond one-to-one with affected participants. These statistical distinctions are important for reading early safety evidence without treating descriptive results as proof of benefit, harm, or equivalence.

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.

Several limitations are specific to the information in this registry record. Allocation was non-randomized and masking was absent, so treatment and control groups cannot be assumed to be comparable. The record does not report adjusted comparisons that could address measured differences, and adjustment would not necessarily resolve unmeasured differences. The sequential design further means that dose groups may represent different cohorts observed at different stages; detailed cohort timing and escalation procedures are not reported.

The adverse-event groups are small, with some containing only 1 participant. The listed counts are therefore limited in their ability to characterize uncommon events or estimate event frequency precisely. No confidence intervals or inferential analyses are reported. Group counts should not be interpreted as stable estimates or as evidence of a dose-response pattern.

The primary endpoint description includes incidence and grade, but the record does not report a complete grade-specific outcome summary. The serious event terms have percentages, but their denominator and counting convention are not reported. Event attribution, timing, duration, resolution and relation to transplantation or study drug are also not reported in the registry record. These details would be important for distinguishing events by cause and clinical course.

The safety analysis population is defined in the record, but participant flow, withdrawals, missing assessments and handling of missing data are not described. The record does not report the protocol’s sample-size justification, interim analyses, stopping rules, or a statistical analysis plan. It lists zero analyses, which indicates that no analyses are listed in the registry record, not that analyses were necessarily absent elsewhere. Secondary outcome categories are listed, but detailed results are not reported in the registry record. Together, these gaps constrain both interpretation and generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety & Tolerability Study of Chimeric Antigen Receptor T-Reg Cell Therapy in Living Donor Renal Transplant Recipients — NCT04817774.
• Registry record last updated 2026-07-02; status last verified 2026-06.
• Results first posted 2026-07-02.
• 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

NCT04817774 is a completed, multicentre, open-label, non-randomized, sequential Phase I/IIa dose-ranging study of TX200-TR101 in living donor kidney transplant recipients. The registry lists enrollment of 26 and a study start date of 2021-03-17, with primary completion on 2024-07-11. Treatment recipients received study drug after transplant; controls underwent transplant without study drug. The primary endpoint concerns treatment-emergent adverse events, including serious adverse events, during 28 days post infusion, graded according to CTCAE V5.0.

The adverse-event record gives affected-participant counts by treatment dose group, control group and donor group. These are descriptive counts from small, non-randomized groups. The registry record lists zero analyses and does not report confidence intervals, a formal statistical comparison, missing-data handling, or a complete grade-specific primary endpoint summary. Detailed results for the listed graft-related and other secondary outcomes are not reported in the registry record.