Autologous CD4 T-Cells in HIV (C34-CXCR4): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Autologous CD4 T-Cells in HIV (C34-CXCR4) (NCT03020524), a non-randomized early/phase 1 study. The primary outcome is The Number of Subjects With Treatment Related Adverse Events.

2. Clinical Question

This was described as a first-in-human pilot study evaluating safety and tolerability. The registry also lists secondary outcomes concerning the percentage of enriched modified cells, change in CD4 count, viral set point measured as log 10 HIV RNA level, and cell-mediated response assessed using flow cytometry. Those outcomes extend the scientific questions to cell persistence or enrichment, immune measures, and virologic measures, but the registry record does not include analysis records for them.

The study can therefore be read as an early safety assessment with exploratory biological measurements, rather than a definitive comparison of clinical benefit. Because there was no randomized comparator, observed outcomes across dose levels cannot by themselves separate dose-related patterns from differences that might arise by chance or from other factors.

3. Trial Design

The registry identifies this as an early-phase 1, completed, non-randomized study with no masking and a parallel model. Its title describes escalating doses, and the brief summary characterizes it as a single-cohort, open-label pilot study of a single infusion. The arm descriptions identify three dose levels; each is an intravenous single dose of autologous, transduced CD4+ T-cells.

The listed dose descriptions are 0.8-1x10\^9 transduced CD4+ T-cells for Dose level 1, 2.4-3x10\^9 for Dose level 2, and 0.8-1x10\^10 for Dose level 3. The adverse-event record lists 3 participants at risk in each dose group. These are small groups, and the study was not randomized. The dose groups therefore do not provide a randomized estimate of the effect of one dose relative to another.

The sponsor was the University of Pennsylvania. The registry lists the study start as 2017-01 and primary completion as 2019-11, with status completed. Enrollment is recorded as 9. The registry does not report further details about dose-escalation decisions, assignment procedures, or whether participants entered the groups in a particular sequence; those details should not be inferred from the dose labels alone.

Open-label means masking was absent, so participants and investigators were not described as blinded to treatment assignment. The record does not report a separate allocation mechanism or a concurrent comparison arm. These design features are relevant when interpreting events: the observed safety pattern is descriptive, and it cannot establish a causal difference between dose levels or against another treatment.

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

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 The Number of Subjects With Treatment Related Adverse Events, measured over one year.

The primary endpoint is the number of participants with treatment-related adverse events. The registry specifies a one-year timeframe and says adverse events were assessed using the DAIDS AE grading table v2.0 November 2014. This is a participant-count endpoint: it concerns whether participants experienced an event judged to be related to treatment, rather than the total number of event episodes or the severity score alone.

Safety and tolerability are central questions in a first-in-human pilot of modified cells because the intervention is being evaluated in people before its effects are well characterized. A prespecified adverse-event endpoint provides a structured way to monitor potential harms over a defined period. The endpoint is also distinct from the listed secondary biological outcomes, such as CD4 count, viral set point, modified-cell percentage, and cell-mediated response.

The registry record names the endpoint but does not include a separate detailed result for the number of participants with treatment-related adverse events. The safety summary separately reports serious and other adverse events by dose level. Those categories should not automatically be equated with treatment-related events: the record does not establish that every other adverse event was considered related to treatment, nor does it provide a full account of causality assessments for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count convey?

A participant-count endpoint records how many people meet a defined event criterion during the stated observation period. It differs from an event count, because one person might experience more than one event. The primary endpoint is framed as participants with treatment-related adverse events over one year. The record does not provide a separate numerical result for that exact endpoint, so the serious and other adverse-event counts should be reported in their own terms rather than substituted for it.

For the safety summaries, the numerator describes participants affected and the denominator describes participants at risk in a dose group. For example, the serious-event figures are 0 of 3 in each listed dose group; the other-event figures are 3 of 3 in each. Such fractions are descriptive. They do not, by themselves, describe the uncertainty around the underlying risk, and they do not establish whether an event was caused by treatment.

Why does uncertainty matter?

A confidence interval is a range of values that reflects the precision of an estimate under a statistical model. A narrow interval indicates greater precision than a wide interval, while a wide interval signals that many underlying values remain compatible with the observed data. For a small safety cohort, uncertainty can remain substantial even when no serious event is observed. Confidence intervals are not reported for the posted safety counts in the registry record.

A p-value, when used, assesses how compatible observed data are with a specified statistical hypothesis under stated assumptions. It does not measure the probability that a treatment works, nor does it quantify the size or clinical importance of an effect. The registry has no analysis records, and no p-values for the listed outcomes are reported. It would be inappropriate to infer a statistical test or an inferential conclusion from the counts alone.

Why is dose-group comparison limited?

Randomization is a method for assigning participants to groups in a way intended to reduce systematic differences at the start of a study. This record describes non-randomized dose groups and no masking. The groups are not a like-for-like randomized control comparison. Differences in observed outcomes could reflect chance, participant characteristics, observation, or other factors, as well as any relationship to dose. Conversely, identical observed counts cannot establish equivalence.

Over-dispersion is a general statistical issue in which observed variation exceeds what a simple model assumes. It can matter when analyzing counts, especially if events cluster within participants or if participants differ in their underlying event propensity. The record does not report a count model, an over-dispersion assessment, or participant-level event data. Thus, no model-based adjustment for such variation can be described.

What does the planning illustration represent?

The planning illustration is described as a calculation based on an observed effect, not as the study’s original design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustration reports the total number of events using the Schoenfeld method; for other outcomes, it reports participants per arm.

These are planning assumptions, not observed results and not observed power. The registry record does not report the study’s own sample-size justification or a protocol-based statistical plan. A planning illustration derived from observed data is sensitive to the observed effect and does not show that the trial was designed prospectively to detect that effect. The record does not give a basis for treating such illustrations as confirmatory evidence.

What analysis details are absent?

The registry does not report an analysis population, a missing-data method, a model for repeated or longitudinal outcomes, or an adjustment strategy for multiple outcomes. The record lists secondary outcomes but does not report their analysis results. It also does not report an interim-analysis plan, a statistical stopping rule, or details of how treatment relatedness was adjudicated. Those omissions limit the ability to reproduce or evaluate inferential analyses, and they should not be filled in by assumption.

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("Dose Level 1", "Dose Level 2", "Dose Level 3")
n      <- c(3, 3, 3)
events <- c(2, 1, 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  Dose Level 1  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2
ARM  Dose Level 2  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6
ARM  Dose Level 3  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 lists a primary safety outcome and secondary outcomes concerning modified-cell percentage, CD4 count, viral set point measured as log 10 HIV RNA level, and cell-mediated response measured using flow cytometry. It records 5 outcome measures overall, but does not report a strategy for controlling multiplicity. When several outcomes are examined, the chance of finding an apparently noteworthy result by chance can increase; methods for addressing that issue may be specified in an analysis plan. No such strategy is reported in the registry record.

The analysis-record count is 0. Statistical results for the secondary outcomes, including estimates, uncertainty intervals, and tests, are not reported in the registry record. The absence of reported analyses does not mean that no measurements were collected; it means the registry record does not provide those analysis results.

Missing-data methods and the handling of withdrawals or incomplete follow-up are not reported in the registry record. The outcome population field is blank, and no analysis population is described. It is therefore not possible to determine from the record whether analyses used all enrolled participants, participants who received an infusion, or another defined group.

The registry also does not report how missing observations would be handled for longitudinal biological outcomes, how event relatedness was assessed, or how protocol deviations were incorporated. These details affect interpretation because analytic choices can influence estimates, especially when groups are small. They should be treated as unreported rather than presumed absent or assumed to follow a standard approach.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety summary lists serious adverse events separately from other adverse events. In each dose group, the serious adverse-event count is 0 among 3 participants at risk, while the other-adverse-event count is 3 among 3 at risk. Deaths are listed as 0 in each group. The serious-event terms list is empty, so no specific serious-event terms are itemized in the registry record.

These categories describe different levels or groupings of events and should not be collapsed into one outcome. The figure for other adverse events indicates participants affected, not the total number of event episodes. The record does not provide event descriptions, grades, timing, or a participant-level account for those other events. It also does not show that all other events were attributed to the intervention.

The primary endpoint concerns treatment-related adverse events during one year. The separate serious and other counts cannot fully answer that endpoint without the corresponding relatedness information. No serious events and no deaths were recorded in these small groups, but that observation does not rule out rare harms or establish comparative safety among dose levels.

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

The results have a limited, descriptive meaning. The registry records no serious adverse events and no deaths in the listed dose groups, while recording other adverse events affecting participants in each group. This is relevant information for an early safety assessment, but the record does not give the detailed event descriptions, timing, severity, or attribution needed for a fuller assessment of the primary treatment-related endpoint.

The observations do not establish that the intervention is safe in a broader population, that a particular dose is safer than another, or that the intervention changes HIV-related outcomes. The study has no randomized comparator, and the groups are small. The record’s secondary outcomes do not have reported analyses, so no conclusion about modified-cell percentage, CD4 count, viral set point, or cell-mediated response can be drawn from the registry results.

A lack of observed serious events is not equivalent to proof that serious events cannot occur. Small studies have limited capacity to characterize uncommon outcomes. Similarly, a pattern of other events across all dose groups is not evidence on its own that those events were caused by treatment. Attribution and event detail are not fully reported.

The most defensible conclusion is therefore about what was recorded, not about a broad treatment effect: the safety summary reports the stated event counts during the study, but the registry record does not provide sufficient comparative or inferential evidence to establish differences between doses or to draw conclusions about clinical benefit. The study’s pilot and early-phase character is central to interpreting that scope.

14. Why This Trial Matters Statistically

This trial is statistically important as an example of the distinction between descriptive safety monitoring and comparative treatment evaluation. A first-in-human, early-phase study can document whether specified events were observed after an intervention and can help characterize what warrants further evaluation. Its small, non-randomized dose groups do not support the same kinds of causal comparisons that a randomized controlled design would aim to provide.

The record also illustrates why an endpoint definition matters. The primary outcome is the number of participants with treatment-related adverse events over one year, while the available safety summary separates serious events from other events. Those are related safety concepts, but they are not interchangeable without treatment-attribution and endpoint-specific results. Clear definitions help prevent readers from treating a broad adverse-event count as if it were the exact primary endpoint.

Uncertainty is another central issue. A zero count is an observed result, not a precise estimate of zero risk. Small groups can leave considerable uncertainty about the range of plausible underlying event rates, particularly for uncommon outcomes. Reporting uncertainty intervals and clear analysis methods would help readers understand how much the observations constrain those possibilities, but such intervals are not reported in the registry record.

Finally, the absence of analysis records for the secondary outcomes limits what can be learned about the biological questions the study also set out to examine. The trial’s statistical contribution should therefore be understood as a limited safety record, not as evidence that settles comparative safety, efficacy, or biological response.

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 main trial-specific limitation is the small size of each dose group: the adverse-event record lists 3 participants at risk in each. Results from groups this small provide limited information about uncommon harms and yield little basis for comparing dose levels. The study was non-randomized, with no masking and no control group, so observed patterns cannot be interpreted as unbiased causal contrasts between doses or against another intervention.

The record describes the study as a single-cohort, open-label pilot and lists a parallel model and dose-level groups. It does not report how participants were assigned to dose levels or the operational rules for escalation. The dose labels alone do not establish the assignment process or the timing of dose decisions.

The primary endpoint is named, but a separate result for participants with treatment-related adverse events is not reported in the registry record. The safety summary gives serious and other adverse-event counts, but not event terms for the other category, severity details, timing, or a complete account of treatment attribution. The record does not report confidence intervals or statistical tests for the safety counts.

Analysis details are also limited. The registry does not report missing-data methods, analysis populations, multiplicity handling, or statistical models for the secondary outcomes. Although several biological outcomes are listed, their analysis results are not reported. These limitations constrain reproducibility and prevent the record from supporting detailed conclusions beyond the descriptive safety counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Autologous CD4 T-Cells in HIV (C34-CXCR4) — NCT03020524.
• Registry record last updated 2022-11-15; status last verified 2022-11.
• Results first posted 2020-11-09.
• 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

NCT03020524 is a completed early-phase 1, open-label, non-randomized pilot study sponsored by the University of Pennsylvania. It evaluated escalating single intravenous doses of autologous CD4+ T-cells modified with a lentiviral vector expressing an HR2, C34-peptide conjugated to the CXCR4 N-terminus in HIV-infected subjects. Enrollment is recorded as 9; the study start is 2017-01 and primary completion is 2019-11.

The primary outcome was the number of participants with treatment-related adverse events during one year, assessed using the DAIDS AE grading table v2.0 November 2014. The safety summary lists 0 serious adverse events and 0 deaths in each dose group, and other adverse events affecting 3 of 3 participants in each group. No analysis records are listed. The non-randomized design, small dose groups, and unreported analysis details limit comparative and causal interpretation.