This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Autologous Polyclonal Tregs for Lupus (NCT02428309), a non-randomized phase 1 study. The primary outcome is Number of Significant Adverse Events (AEs) Through Week 48.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02428309 |
| Phase | Phase 1 |
| Condition | Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
The study asked whether autologous polyclonal regulatory T-cell therapy could be administered to adults with active cutaneous lupus with acceptable safety and tolerability, and how safety findings might inform dose selection for later research. It was a Phase I study, not a randomized comparison of treatment against a control. The registry describes a sequential dose-escalation plan with low-, medium-, and high-dose cohorts, each intended to receive a single infusion.
The primary outcome was the number of significant adverse events from signed informed consent through Week 48. A significant event was defined as either a related Grade 3 or higher adverse event under the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0, or a related serious adverse event. The safety review committee determined whether an event was possibly, probably, or definitely related to the cell therapy.
The planned clinical setting was cutaneous lupus, including adults with skin involvement. The study also listed systemic lupus and discoid lupus among its conditions. Its rationale noted that skin disease could allow clinical effects to be detected and background therapy to be controlled, while enabling research analyses in blood and skin. The registry record does not report results for those broader clinical or mechanistic aims.
Only one participant was enrolled, and the primary-outcome population is described as that participant receiving a single low-dose infusion. Consequently, the posted record addresses safety observations for a very small exposure, rather than comparative efficacy or a dependable estimate of event frequency across the planned dose levels.
3. Trial Design
This was a Phase I, open-label, non-randomized, sequential dose-escalation study sponsored by the National Institute of Allergy and Infectious Diseases. The intervention was ex vivo expanded human autologous polyclonal regulatory T cells. Participants were not masked, and the design did not include a like-for-like control group. The registry lists an enrollment of 1 and a status of terminated. The start date was 2015-08-27, and the primary completion date was 2016-09-02.
The planned low-dose cohort was to receive one infusion of 1 x 10^8 autologous polyclonal Tregs. The medium-dose cohort was planned to receive one infusion of 4 x 10^8 cells, and the high-dose cohort one infusion of 16 x 10^8 cells. The cohort descriptions specify sequential escalation and an intended enrollment of 3-6 participants per cohort. The observed enrollment of 1 means the record does not describe experience across all three planned dose levels; the primary-outcome population is specifically identified as a single participant in the low-dose cohort.
Sequential dose escalation is a design in which experience at an earlier dose informs progression to a later dose. It can support cautious early safety assessment, but it does not create a randomized comparison. Without a concurrent control group, changes in disease activity or events cannot be attributed to treatment by comparing assigned groups.
The study listed a primary safety outcome through Week 48 and secondary outcomes extending through Week 152, as well as infusion-related events within 24 hours. Other planned measures included lupus flares, laboratory changes, and adverse events. The reason for termination, details of dose-escalation decisions, eligibility criteria beyond the described population, and the operational stopping rules are 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
| Stage | Dose 1 (1x10^8) |
|---|---|
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: One participant enrolled in the study that received a single infusion of 1 x 10\^8 autologous polyclonal Tregs (ex vivo selected and expanded)
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: Participant received a single infusion of 1 x 10\^8 autologous polyclonal Tregs (ex vivo selected and expanded).
| Characteristic | Unit | Dose 1 (1x10^8) |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 46 (SD NA) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Significant Adverse Events (AEs) Through Week 48, measured over From time of signed informed consent to Week 48.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint counts significant adverse events occurring from the time of signed informed consent through Week 48. The registry defines a significant event as a related Grade 3 or higher adverse event under the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0, or any related serious adverse event. Relatedness could be classified as possibly, probably, or definitely related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.
This endpoint is suited to an early-phase study because safety and tolerability are central questions when a cell therapy is first evaluated in a small group. Combining severe events with serious events gives the study a way to capture clinically important safety signals, while requiring a relationship assessment focuses the endpoint on events considered potentially associated with the intervention. The registry's definition does not make every event occurring after infusion a treatment-related event.
The endpoint is a count of events, not a measure of disease improvement. The record identifies one participant as the primary-outcome population but does not provide an explicit primary-endpoint count or an event-level account connecting the adverse-event summary to the endpoint's criteria. Therefore, the serious-event listing alone cannot establish the number of qualifying significant events through Week 48.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main interpretive constraint is the scale of the study. The registry reports enrollment of 1, and the primary-outcome population is one participant who received a single infusion of 1 x 10^8 autologous polyclonal Tregs. The record therefore documents limited experience at the low dose; it does not provide observed experience at the planned medium or high doses. Findings from this enrollment cannot characterize the range of safety outcomes that might occur across the intended dose-escalation program.
The adverse-event summary lists one participant at risk for serious adverse events and one affected participant in Dose 1 (1x10^8). It also lists peripheral neuropathy as the top serious-event term at 100.0%. These entries describe the posted safety summary, not a comparative treatment effect. The record lists 0 deaths. A single participant's experience cannot establish how often such events would occur in a broader population, and the percentage attached to the event term should not be read as a stable estimate of risk.
The primary endpoint has a specific definition: related Grade 3 or higher events or related serious adverse events through Week 48. The adverse-event summary does not itself say whether the listed serious event met the endpoint's relationship criteria, nor does it provide the committee's attribution assessment or an explicit endpoint count. The event listing should therefore be distinguished from a confirmed primary-endpoint result. The registry record does not report enough detail to resolve that link.
No randomized allocation, masking, or control arm was used. As a result, there is no direct between-group estimate of treatment effects, and changes in disease activity cannot be separated from other influences using this design alone. The planned measures include lupus flares and laboratory changes, but results for those outcomes are not reported in the registry record.
The registry lists 20 outcome measures and 0 analyses. That means the posted record does not contain a set of inferential results with which to assess precision, uncertainty, or consistency across outcomes. It does not report confidence intervals or a statistical analysis plan. For a one-participant safety observation, descriptive reporting is more informative than claims about population-level rates, but the event details and endpoint linkage remain important for interpreting even that description.
Overall, the record documents a terminated, very small Phase I study and a serious-event summary for its low-dose participant. It does not establish comparative efficacy, characterize safety across all planned doses, or provide a precise estimate of adverse-event frequency. The reason the study terminated is not reported in the registry record.
9. Statistical Methods Explained
The registry describes a non-randomized, open-label, sequential study. These design features determine what statistical conclusions are possible. Non-randomized means participants were not allocated by chance among treatment and control groups. Open-label means treatment assignment was not masked. Sequential escalation means the plan was organized around progressing through dose levels rather than comparing concurrent randomized groups. These features suit an early safety investigation, but they limit causal comparisons and make the small amount of observed experience especially important.
What does a count endpoint convey?
The primary outcome is a number of significant adverse events during a specified follow-up window, rather than a continuous measurement or a time-to-event estimate. A count can describe how many events were recorded, but its interpretation depends on the event definition, follow-up, and completeness of event reporting. In this study, an event qualified for the primary endpoint only if it met the severity or seriousness criteria and was judged related according to the registry definition. The posted adverse-event summary does not supply all those details for the listed serious event.
Counts can also distinguish the number of events from the number of participants who experienced events. One participant may experience more than one event, so those quantities are not interchangeable. The registry's adverse-event summary reports participants at risk and affected, and separately identifies an event term. It does not provide a full event-level listing in the registry record reported in the registry record. The primary outcome title refers to the number of events, so a participant-level affected count should not automatically be treated as the primary endpoint count.
Why does a small enrollment limit precision?
Statistical precision describes how narrowly a result constrains the range of plausible values for the underlying quantity. With one enrolled participant, the observations describe that participant's experience; they cannot reliably map the distribution of outcomes among a wider population. Even a clearly described event does not, by itself, give a precise population event rate. Confidence intervals can express uncertainty around estimates, but no confidence interval for the primary outcome is reported in the registry record.
General statistical reasoning also cautions against treating the absence of a reported event as evidence that an event cannot occur. In a very small study, the observed data cover little exposure. Here, the registry does list a serious adverse event in the low-dose cohort, but the record does not give a complete event-level account or explicitly identify the primary endpoint count. The study's limited enrollment and termination further constrain how much can be inferred about the planned escalation.
What would a comparison require?
A comparative treatment estimate generally relies on a defined contrast between groups. This study has no randomized control group, and its registry entry explicitly identifies the design as non-randomized. Any numerical comparison between its dose cohorts would also be problematic because the record reports only one enrollee, in the low-dose population. The planned medium- and high-dose cohorts are not represented in the stated primary-outcome population. Thus, the evidence cannot estimate a dose-response pattern or distinguish treatment effects from other causes of observed changes.
For general context, randomization helps balance both measured and unmeasured characteristics between groups on average; it does not guarantee balance in every small study. Masking can reduce some forms of expectation or assessment bias. Neither feature is present. These general concepts explain why a single-arm, open-label observation is chiefly descriptive and why conclusions should be limited to the reported safety experience.
How should planning illustrations be read?
The registry record gives assumptions for planning illustrations based on an observed effect: 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. Those are modeling assumptions, not features of the actual non-randomized, single-participant experience. The record does not report the numerical planning outputs in the registry record described for this study. Any such illustration should be understood as participants per arm for a hypothetical future comparison, not as observed power or evidence that the current study had a particular probability of detecting an effect.
General sample-size calculations depend on the outcome, variability or event pattern, target effect, and analysis assumptions. For count outcomes, over-dispersion matters when event counts vary more than a chosen statistical model expects: failing to account for it can make uncertainty appear too small. The registry does not report a count model or an over-dispersion assessment. Given the small observed enrollment, assumptions estimated from the trial itself would in any case be highly uncertain.
What information is needed for fuller inference?
Interpretation of the primary endpoint would benefit from an explicit qualifying event count, event-level severity and timing, the relatedness determination, and a clear description of the population included in the analysis. A prespecified analysis plan would clarify how repeated events, incomplete follow-up, and multiple outcomes were to be handled. These details are not reported in the registry record. Without them, the appropriate statistical reading is descriptive: the record gives limited safety observations, but not a complete inferential analysis of the primary endpoint or the wider clinical aims.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures, including the primary significant-adverse-event outcome and secondary measures involving adverse events, lupus flares, infusion-related events, and laboratory changes. Evaluating many outcomes can raise a multiplicity issue: when many statistical tests are conducted, the chance of at least one apparently notable result can increase. General approaches include prespecifying a primary outcome, controlling error across selected tests, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy or a statistical analysis plan.
The record lists 0 analyses. It therefore does not provide inferential results across the outcomes, nor does it describe adjustments or prioritization among them. The number of outcomes alone does not establish that multiple statistical tests were performed; the registry record does not report such testing.
Missing-data handling and analysis populations are also not reported in the registry record. The primary-outcome population is described as one enrolled participant who received a low-dose infusion, but the record does not explain how incomplete follow-up, unobserved outcomes, or exclusions would be handled. It does not report whether the planned outcomes were analyzed in an intention-to-treat, treated, or other defined population.
Because enrollment was 1 and the study was terminated, the distinction between planned and observed follow-up is especially important. The listed secondary outcomes include measures extending through Week 152, but results and completeness of follow-up for those outcomes are not reported in the registry record. No assumption about missing outcomes or analysis populations should be made from the planned outcome descriptions alone.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Dose 1 (1x10^8) | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dose 1 (1x10^8) | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dose 1 (1x10^8) | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Dose 1 (1x10^8) |
|---|---|---|
| Neuropathy peripheral | Nervous system disorders | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dose 1 (1x10^8) |
|---|---|---|
| Pericarditis | Cardiac disorders | 1 of 1 |
| Oedema peripheral | General disorders | 1 of 1 |
| Hypokalaemia | Metabolism and nutrition disorders | 1 of 1 |
| Cutaneous lupus erythematosus | Skin and subcutaneous tissue disorders | 1 of 1 |
Serious events with the highest arm-level rate: neuropathy peripheral (100.0%).
The adverse-event summary lists Dose 1 (1x10^8), with one participant at risk and one affected for serious adverse events. It lists 0 deaths and identifies peripheral neuropathy as the top serious-event term at 100.0%. These are descriptive entries for the small observed cohort. The percentage is the registry's reported value and should not be treated as a precise population estimate.
The primary endpoint is narrower than a general serious-event summary in one important respect: it counts events judged related to the cell therapy, and includes related serious events or related Grade 3 or higher events through Week 48. The registry's summary does not explicitly connect the listed peripheral neuropathy event to the primary endpoint's relationship assessment, nor does it provide a separate explicit primary-endpoint count. Therefore, the adverse-event summary should not be substituted for a confirmed count of qualifying primary events.
Seriousness, severity grade, and causal relatedness are distinct descriptions. The registry defines the endpoint using seriousness or Grade 3 or higher severity together with a relationship assessment. Details of the event's grade, timing, and committee attribution are not reported in the registry record. These limitations matter when interpreting a single participant's safety experience.
12. What the Result Does, and Does Not, Mean
The record documents a Phase I safety study of autologous polyclonal regulatory T cells for adults with active cutaneous lupus. It reports one enrollee, whose primary-outcome population is described as receiving a single low-dose infusion. The adverse-event summary lists one participant affected by a serious adverse event, reports peripheral neuropathy as the top serious-event term at 100.0%, and lists 0 deaths. These are the concrete safety observations available in the registry record.
Those observations do not establish a general rate of serious adverse events. A single participant cannot represent the range of experiences in a larger population, and the percentage attached to the event term is not a precise estimate for future participants. Nor does the serious-event summary alone establish the primary endpoint result, because the endpoint requires a relatedness determination and includes specific severity or seriousness criteria. An explicit count of events meeting that endpoint definition is not reported in the registry record.
The record also does not establish that the intervention improves cutaneous lupus or changes systemic disease activity. The study was non-randomized and had no control group, and results for disease activity outcomes are not reported in the registry record. The planned medium- and high-dose cohorts are not represented in the stated primary-outcome population, so the record cannot describe safety across all intended dose levels or compare doses.
The study's stated aim was to assess safety, tolerability, and effects of different doses to support dose selection for a future larger efficacy trial. The enrollment and posted information do not provide a basis for a comparative efficacy conclusion or a reliable estimate of treatment effect. The registry record does not report why the study was terminated or whether any planned dose-escalation decisions were reached.
The most defensible reading is narrow: the registry records a limited safety experience in one low-dose participant and a serious-event listing. Broader conclusions about safety, efficacy, dose response, or outcomes in adults with lupus are not supported by this record alone.
13. Why This Trial Matters Statistically
Early-phase studies serve a different statistical purpose from large comparative trials. Their central questions often concern whether an intervention can be administered and what safety signals warrant further investigation. This study's primary outcome reflects that purpose: it focuses on significant adverse events, with severity, seriousness, and relatedness defined in advance in the registry description.
The trial is also a useful example of why the design and enrollment must accompany any reading of an event percentage. The registry reports one enrolled participant, in the low-dose primary-outcome population, while the planned design described three sequential dose cohorts. A serious-event term reported at 100.0% in this setting is a description of the observed summary, not a stable estimate that can be generalized to other participants or doses. The scale and context of a percentage are essential to its interpretation.
The non-randomized, open-label design makes the distinction between observation and causal comparison especially important. Without a control group, the study cannot estimate what would have happened under an alternative treatment or no study intervention. Without representation of the planned dose levels in the stated outcome population, it cannot characterize a dose gradient. These are design limits, not shortcomings that can be repaired by rephrasing the observed count.
The registry also illustrates the importance of endpoint alignment. A broad serious-adverse-event summary and a primary endpoint requiring relatedness and specified severity criteria are not automatically equivalent. Clear reporting of event-level details and endpoint counts helps readers understand how descriptive safety listings map to the prespecified question.
Finally, a planned future efficacy trial depends on transparent early safety reporting, but the current record should not be mistaken for evidence from that later comparison. Its statistical value lies in documenting what was recorded and in clarifying how much remains uncertain when enrollment is very small and analyses are not posted.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation is the enrollment of 1. The primary-outcome population is a single participant receiving the low dose, so there is little basis for estimating population-level event frequencies or describing variability across participants. The planned cohort sizes and higher doses do not change the amount of observed evidence reported in the record.
The study was terminated, but the reason is not reported in the registry record. The registry does not report whether termination was related to safety, recruitment, operational issues, or another cause, so no explanation should be inferred. It also does not describe whether the planned sequential escalation proceeded beyond the low-dose cohort.
The primary endpoint requires a relatedness judgment and a defined severity or seriousness threshold. Although the adverse-event summary lists a serious event and identifies peripheral neuropathy, the record does not report the event-level grade, timing, or committee determination needed to connect that listing unambiguously to the primary endpoint. The explicit primary-endpoint count is not reported in the registry record.
Other limitations include the open-label design and lack of randomization or a control group. The record provides no inferential analyses, confidence intervals, or statistical analysis plan. It does not report the handling of missing data, the analysis populations, or a multiplicity strategy. Results for the planned disease activity, laboratory, and longer-term outcomes are not reported in the registry record. These omissions restrict interpretation but do not justify assumptions about unreported outcomes or procedures.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Autologous Polyclonal Tregs for Lupus — NCT02428309.
- Registry record last updated 2019-11-12; status last verified 2019-10.
- Results first posted 2019-11-12.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02428309, titled “Autologous Polyclonal Tregs for Lupus,” was a Phase I, open-label, non-randomized, sequential dose-escalation study sponsored by the National Institute of Allergy and Infectious Diseases. It evaluated ex vivo expanded human autologous polyclonal regulatory T cells in adults with active cutaneous lupus. Planned cohorts were assigned single infusions at low, medium, and high dose levels.
The registry reports enrollment of 1, a terminated status, and a primary safety endpoint counting significant adverse events through Week 48. The primary-outcome population is described as one participant receiving a low-dose infusion. The adverse-event summary lists one participant affected by a serious adverse event, peripheral neuropathy at 100.0% among the top serious-event terms, and 0 deaths.
The record lists 20 outcome measures and 0 analyses. It does not report a definitive primary-endpoint count, results across the planned dose levels, or inferential estimates for efficacy or safety.