PRO 140 in Treatment-Experienced HIV-1 Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PRO 140 in Treatment-Experienced HIV-1 Subjects (NCT03902522), a na phase 2, phase 3 study. The primary outcome is Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the Initial 1-week Treatment Period.

2. Clinical Question

3. Trial Design

NCT03902522 is titled “PRO 140 in Treatment-Experienced HIV-1 Subjects.” Its official title describes a multi-center, two-part, single-arm, open-label, 25-week trial. The study is listed as Phase 2 and Phase 3, with an enrollment of 6. The registry lists HIV-1 infection as the condition and CytoDyn, Inc. as sponsor. The recorded status is completed; the study start is 2018-06-25 and primary completion is 2020-05-18.

The brief summary describes two treatment periods. The initial one-week period evaluates PRO 140 in combination with failing ART. The subsequent 24-week period evaluates PRO 140 in combination with optimized background therapy. The arm description states that participants remained on existing ART for one week, then received PRO 140 700 mg weekly by subcutaneous injection with existing ART for the next week, before entering the later open-label treatment period. The description of the later regimen is truncated, so its full details are not reported in the registry record.

The allocation is listed as not applicable, masking as none, and the model as single group. This design can describe outcomes observed during treatment, but it does not provide a randomized concurrent control for separating treatment effects from other influences. The registry also lists 8 outcome measures and 0 analyses. The record does not report additional details of the statistical analysis plan, sample-size justification, or interim analyses.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The Intent-to-Treat (ITT) population is defined as the set of subjects who are enrolled and have received at least one dose of PRO 140. Subjects who discontinue from the study prior to their first post-baseline assessment will be included in the ITT population and analyzed as non-responders in the primary safety analysis

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: The Intent-to-Treat (ITT) population is defined as the set of subjects who are enrolled and have received at least one dose of PRO 140. Subjects who discontinue from the study prior to their first post-baseline assessment will be included in the ITT population and analyzed as non-responders in the primary safety analysis

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the Initial 1-week Treatment Period, measured over 1-week from baseline to the end of the initial PRO 140 and ART treatment period.

The primary endpoint is the proportion of participants with at least a 0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the initial one-week treatment period. It is a responder endpoint: each participant is classified according to whether the specified reduction threshold was met, and the endpoint concerns the proportion classified as responders.

Viral load is measured as HIV-1 RNA, and the endpoint focuses on change relative to baseline rather than a single absolute level. A threshold-based endpoint can provide a readily interpretable summary of how many participants reached a prespecified degree of change. It also differs from an endpoint based on the average change across all participants, which retains the magnitude of each participant’s change rather than reducing it to responder status.

The registry record states the endpoint definition and timeframe but does not report the observed responder count or proportion. The endpoint’s population field describes an Intent-to-Treat population as enrolled subjects who received at least one dose of PRO 140 and indicates that participants stopping before the first post-baseline assessment were to be treated as non-responders. The rest of that population description is incomplete in the registry record. Without the outcome count and a complete account of the analysis, the endpoint definition alone does not establish the trial’s result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a responder proportion represent?

The primary endpoint classifies participants according to whether they reached the stated HIV-1 RNA reduction threshold by the end of the initial one-week treatment period. A proportion is a summary of the number meeting the definition relative to the analyzed population. It is not an average change in viral load, and it does not show how far each responder exceeded the threshold. The registry record provides the definition but not the observed count or proportion.

How does this differ from a mean change?

The listed secondary outcomes include mean changes from baseline in HIV-1 RNA and CD4 cell count. In general, a mean summarizes the average change while retaining the scale of the measurement. A responder proportion instead applies a cutoff and groups participants into response categories. These summaries answer different questions: the mean describes average change, while a threshold proportion describes how many meet a specified criterion. Neither result can be recovered from the endpoint descriptions alone.

What would a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate under a stated statistical method. For a responder proportion, it would help show how precisely the observed proportion is estimated. The interval’s width depends on the data and method, among other considerations. The registry record does not report a confidence interval for the primary endpoint, so no interval-based assessment is available.

Why does the design affect interpretation?

The trial is listed as single group, open label, with allocation not applicable and masking absent. A single-group study can document what happened among participants receiving the study regimen, but it does not include a randomized concurrent comparison group. Thus, a change from baseline alone cannot establish what would have happened over the same period without the study treatment. In general, randomization helps balance measured and unmeasured factors between groups; that design feature is not present in this study as recorded. Open-label status means participants and investigators were not masked to treatment, although the record does not describe how this affected outcome assessment.

How should the treatment periods be understood?

The brief summary separates an initial one-week period involving PRO 140 with failing ART from a subsequent 24-week period involving PRO 140 with optimized background therapy. The primary endpoint belongs to the initial period. Outcomes measured later address different timepoints and treatment context, so they should not be treated as interchangeable with the primary endpoint. The complete description of the later regimen is not reported in the registry record.

What does the analysis-population description say?

The registry defines the Intent-to-Treat population as subjects enrolled and receiving at least one dose of PRO 140. It also says that participants who discontinue before their first post-baseline assessment are included as non-responders, but the description ends before fully specifying the analysis. In general, an analysis population determines which participants contribute to an estimate and how participants with missing assessments are handled. The incomplete wording limits assessment of the intended analysis. Further missing-data procedures and the full statistical analysis plan are not reported in the registry record.

What about multiplicity?

The record lists 8 outcome measures, including the primary endpoint and several secondary outcomes. When multiple outcomes are examined, the chance of obtaining an apparently notable result by chance can increase, depending on the analyses and interpretation. In general, statistical plans may specify how to address multiple comparisons or distinguish confirmatory from exploratory outcomes. Such a plan is not reported in the registry record. The number of outcome measures alone does not indicate which analyses were performed or whether adjustment was used.

How should planning illustrations be read?

In general, sample-size calculations are planning exercises based on assumptions about the effect, significance level, allocation, and statistical method. The stated planning assumptions describe illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These assumptions do not describe the single-group trial’s own design, and a planning illustration is not observed power. The record does not report a trial-specific sample-size justification.

Why can over-dispersion matter?

In general, over-dispersion occurs when variability in count or rate data exceeds what a simple model assumes. If present and unaddressed, standard errors and confidence intervals from that simple model can be too small, making results appear more precise than they are. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a model-based analysis of the primary endpoint, so no claim about over-dispersion in this trial is warranted.

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("Leronlimab (PRO 140)")
n      <- c(5)
events <- c(0)
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  Leronlimab (PRO 140)  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the primary responder endpoint and secondary virologic and CD4 outcomes. Looking at multiple outcomes can raise multiplicity concerns: in general, the more statistical comparisons made, the greater the chance that some may appear notable by chance. A prespecified analysis plan can explain which outcomes are confirmatory and whether adjustment or another strategy is used. That information is not reported in the registry record. The record also lists 0 analyses, so it does not provide a set of outcome estimates to evaluate for multiplicity.

The registry’s description of the Intent-to-Treat population says it includes enrolled subjects who received at least one dose of PRO 140, and that participants discontinuing before their first post-baseline assessment are included as non-responders. The remainder of that sentence is incomplete. Further details about missing measurements, later discontinuations, or sensitivity analyses are not reported in the registry record. These details matter because missing-data handling can affect both the analysis population and the estimated responder proportion.

Interim analyses and the full statistical analysis plan are not reported in the registry record. No assumptions about their existence or conduct can be made from the outcome list alone. The absence of these details limits assessment of how outcome selection, missing observations, and multiple analyses were handled.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: back pain (16.7%), myocardial infarction (16.7%).

The registry lists serious adverse event information in two treatment-group entries. For “Leronlimab (PRO 140) + Existing ART,” 6 participants are listed at risk, with 0 affected by serious adverse events and 0 deaths. For “Leronlimab (PRO 140) + OBT,” 6 participants are listed at risk, with 2 affected and 0 deaths. The listed serious event terms are Back Pain and Myocardial infarction, each reported as 16.7%.

These are descriptive figures from the registry record. The entries should not be treated as a randomized comparison: the trial is listed as single group, and the record does not establish the entries as like-for-like control arms. Nor do the event listings establish that PRO 140 caused an event. Causal attribution and fuller clinical context are not reported in the registry record. The two group entries should be read as recorded, without assuming whether the same participants contributed across treatment periods. The figures describe reported serious events, not the full safety profile or a comparative estimate of risk.

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

The registry record establishes that NCT03902522 was a completed, single-arm, open-label trial of PRO 140 in treatment-experienced subjects with HIV-1 infection. It describes a primary endpoint focused on the proportion reaching at least a 0.5 log10 reduction in HIV-1 RNA viral load at the end of the initial one-week treatment period. It also outlines a subsequent 24-week treatment period and lists secondary virologic and CD4 outcomes.

The record does not report the primary endpoint result or the secondary outcome results in the information available for this analysis. It therefore cannot show how many participants reached the primary threshold, the magnitude of any average changes, or the precision of those estimates. Endpoint definitions and study objectives indicate what the trial intended to assess; they are not evidence of the observed findings.

The single-group design and absence of masking also set limits on what could be inferred from observed changes. Without a randomized concurrent control, the study cannot directly estimate a between-group treatment contrast. In general, before-and-after observations may reflect multiple influences, and an open-label design does not conceal treatment assignment. These design features do not erase the descriptive value of observations, but they constrain causal interpretation.

The serious adverse event listings report two affected participants in the PRO 140 plus OBT entry and two serious event terms at 16.7% each; they do not establish causation or provide a controlled safety comparison. Overall, the record describes the trial question, design, and selected safety information, but it does not contain enough outcome results to support a conclusion about the primary endpoint’s observed effect or its precision.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a clearly described endpoint and an unreported endpoint result. The primary question is defined as a threshold-based change in HIV-1 RNA over the initial one-week treatment period. That definition helps identify the intended estimand, but interpretation still requires the observed responder count or proportion and an account of uncertainty. The registry record does not report those values.

The study also illustrates why design labels matter. A single-arm, open-label trial can describe outcomes among participants receiving a regimen, but it does not furnish a randomized concurrent comparison. Readers therefore need to distinguish observed change from a causal treatment contrast. That distinction is especially important when a trial includes different treatment periods and later outcomes measured under a different background-therapy context.

The listed secondary measures cover both threshold outcomes and continuous outcomes, including HIV-1 RNA and CD4 cell count. These endpoints capture different aspects of response and require different summaries. Listing several outcomes also makes the statistical plan relevant: prespecification, multiplicity handling, and missing-data methods help readers understand how analyses were intended to be interpreted. Those details are not reported in the registry record.

Finally, the record’s small enrollment and serious-event listings underscore the importance of precision and cautious description. A safety event count is not by itself a comparative risk estimate or evidence of causality. The most useful statistical reading is therefore bounded: recognize what the design and endpoints specify, and distinguish those details from results that the registry record does not report.

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 enrollment was 6, and the study model is single group. This limits the amount of outcome information available and provides no randomized control group for a direct comparison. The trial is also listed as open label, with masking recorded as none. Observed changes can be described, but causal interpretation is constrained by these design features.

The registry gives the primary endpoint definition but does not report its result. The secondary outcome list likewise describes measures without providing the findings in the information available for this analysis. Confidence intervals and other measures of precision for efficacy outcomes are not reported in the registry record. As a result, neither effect magnitude nor uncertainty can be assessed for those outcomes.

Some details are incomplete. The arm description for the 24-week period is truncated, as is the full description of the Intent-to-Treat analysis population. Further information about missing-data procedures, multiplicity handling, interim analyses, and the statistical analysis plan is not reported in the registry record. The full sample-size justification is also not reported.

The serious adverse event information is descriptive and does not establish causality. The group entries do not constitute a randomized comparison, and the registry record does not clarify whether the same participants contribute to both entries. These limits make the figures unsuitable for inferring a comparative safety effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PRO 140 in Treatment-Experienced HIV-1 Subjects — NCT03902522.
• Registry record last updated 2025-09-16; status last verified 2025-08.
• Results first posted 2025-09-16.
• 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

NCT03902522 is a completed, multi-center, single-arm, open-label trial of PRO 140 in treatment-experienced subjects with HIV-1 infection. It is listed as Phase 2 and Phase 3, with enrollment of 6. The trial description includes an initial one-week period involving PRO 140 with existing ART and a subsequent 24-week period involving optimized background therapy.

The primary endpoint is the proportion with at least a 0.5 log10 reduction in HIV-1 RNA viral load at the end of the initial one-week period. The registry record does not report the primary endpoint result. It lists 8 outcome measures and 0 analyses. Serious adverse event entries include 2 affected participants in the PRO 140 plus OBT group and no deaths in either listed group. The record does not establish a randomized safety comparison or causal attribution.