An Extension Protocol for Virologically Suppressed Subjects Who Successfully Completed PRO140_CD03 Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Extension Protocol for Virologically Suppressed Subjects Who Successfully Completed PRO140_CD03 Study (NCT05271370), a non-randomized phase 2, phase 3 study. The primary outcome is Long Term Clinical Safety of PRO 140 Monotherapy by Assessing the Number of Participants With Grade 2, 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale, and the Number of Participants With Treatment-emergent Serious Adverse Events..

2. Clinical Question

3. Trial Design

This was a Phase 2b/3 multicenter extension study for participants who were virologically suppressed and had successfully completed PRO140 CD03. The registry lists Phase 2 and Phase 3, non-randomized allocation, no masking, and a parallel-group model. Its enrollment was 56. The registry status is terminated; a reason for termination is not reported in the registry record.

The three listed treatment groups received weekly subcutaneous injections of PRO 140 at 350 mg, 525 mg, or 700 mg. The brief summary describes continuing monotherapy after an initial 48 weeks and notes a one-week overlap with the existing retroviral regimen at the end of treatment for participants without virologic failure. The primary safety observation period was from the first treatment administration to the last treatment visit, up to 197 weeks.

Because allocation was non-randomized and masking was absent, group membership was not assigned through a randomized, blinded comparison, as far as the registry record states. It does not report how participants entered each dose group, whether dose groups differed in relevant characteristics, or whether any statistical adjustment was planned. Those details matter when interpreting differences across groups: observed group counts alone cannot establish that dose assignment caused a difference.

The study focused on long-term safety, antiviral activity, and tolerability during extension treatment. The listed secondary outcomes include time to virologic failure, viral re-suppression after failure, re-suppression after restarting the previous baseline antiretroviral regimen, and mean change in CD4 cell count. Numerical analyses for these outcomes 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety population is defined as all subjects who received at least one dose of PRO 140 within the PRO 140\_CD03 extension 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.

Population: All patients who received at least one dose of PRO 140 (leronlimab) were included in the baseline analysis population. Study was early terminated.

6. Primary Endpoint

The registry lists the primary outcome as Long Term Clinical Safety of PRO 140 Monotherapy by Assessing the Number of Participants With Grade 2, 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale, and the Number of Participants With Treatment-emergent Serious Adverse Events., measured over From TE1 (first treatment administration) to last treatment visit, up to 197 weeks.

The primary endpoint concerns participant counts for two safety outcomes: adverse events graded 2, 3, or 4 under the DAIDS adverse-event scale, and treatment-emergent serious adverse events. The registry describes the DAIDS scale as ranging from Grade 1, mild, through Grade 5, death; the primary endpoint focuses on Grades 2 through 4 for the graded-event component. The separate serious-event component is defined by seriousness and treatment timing: a treatment-emergent serious adverse event has onset on or after the first treatment.

Severity grading and serious-event status capture related but distinct aspects of safety. A severity scale describes how serious an event is, while the serious-event definition used in the registry is based on the event meeting serious-adverse-event criteria and beginning during or after treatment starts. Counting participants with these outcomes can describe how many people experienced events over the specified treatment period. It is an especially relevant descriptive measure for an extension intended to examine longer-term exposure.

The registry specifies the safety population as subjects who received at least one dose of PRO 140 in the extension. It does not report numerical results for the primary endpoint, nor does it report an estimate of uncertainty for those results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The available record supports a descriptive reading of participant counts, rather than a reconstruction of an inferential analysis. The primary outcome is defined in terms of the number of participants experiencing specified safety outcomes. For a binary outcome, each participant is classified according to whether the event occurred during the defined observation period. Counts can communicate how many participants were affected, but a count alone does not show the uncertainty around an underlying event probability or account for differences in exposure time.

What does a confidence interval add?

In general, a confidence interval describes the precision of an estimated quantity under a stated statistical method. A narrower interval indicates greater precision; a wider interval indicates less precision. The registry record does not report confidence intervals for the primary safety outcomes or the adverse-event group counts, so their statistical precision cannot be assessed from the posted results. A confidence interval would not, by itself, remove bias from non-randomized allocation or establish that a treatment caused an outcome.

What do the group counts describe?

The safety entries give the number at risk and the number affected for each recorded adverse-event category and dose group. They are useful for describing the observed experience in those groups. They are not a randomized comparison. In a non-randomized study, groups may differ for reasons other than the assigned dose, and the registry record does not report how such differences were addressed. The entries also do not report how long each participant was observed, so they should not be treated as exposure-adjusted rates.

What is the role of the safety population?

The primary endpoint description defines the safety population as all subjects who received at least one dose of PRO 140 within the extension study. This definition identifies who would be included in the stated safety assessment. Enrollment and the safety population are not interchangeable concepts: enrollment describes the study’s listed enrollment, while the safety definition depends on receiving treatment. The record does not provide a participant flow or state how many enrolled participants received at least one dose.

How should the planning illustrations be understood?

General sample-size illustrations are planning exercises, not evidence about what the trial observed or what it had power to detect after completion. The stated assumptions for these illustrations 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 is based on the total number of events, while other outcomes are expressed as participants per arm. These assumptions describe the planning calculations, not a reported analysis plan for this trial. The registry record does not report the trial’s own sample-size justification, target effect, or statistical plan.

In general, event-count methods and participant-count methods answer different planning questions. A time-to-event analysis uses the number of events because the information available depends on events observed, while a binary-outcome calculation concerns participants with or without an event. A normal approximation is a modeling convenience for an illustration; it does not guarantee that a planned analysis would be appropriate for every observed dataset. The registry record does not describe an actual model, test, or method for estimating time to virologic failure.

What cannot be inferred from the record?

The record reports no analysis results for the primary outcome, and lists zero analyses. It also does not describe confidence-interval methods, adjustment for baseline differences, handling of repeated measurements, censoring rules, or a prespecified approach to missing data. General statistical methods can clarify what such choices would mean, but they cannot substitute for an analysis plan or numerical results that are not reported. No recalculated comparison or estimate can be recovered from the listed counts alone without making additional assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and identifies the safety endpoint as primary, alongside secondary outcomes concerning time to virologic failure, re-suppression, and CD4 cell-count change. It does not report how the number of outcomes was handled statistically, whether any outcomes were grouped into a testing hierarchy, or whether adjustments for multiple comparisons were planned. A multiplicity strategy is not reported in the registry record.

In general, evaluating many outcomes or comparisons can increase the chance of finding an apparently notable result by chance. A prespecified strategy can clarify which results are confirmatory and how uncertainty should be interpreted across several tests. The absence of a reported strategy does not show that no strategy was used; it means the registry record does not describe one. The record lists zero analyses, so there are no reported statistical tests to assess for multiplicity.

The primary safety population is defined as subjects who received at least one dose of PRO 140 in the extension. Other analysis populations, including populations for the virologic or CD4 outcomes, are not reported in the registry record. The record does not specify whether participants were analyzed according to treatment received, treatment group at entry, or another rule.

Details on missing observations are also not reported in the registry record. It does not state how incomplete outcome measurements, withdrawals, loss to follow-up, or missing event information were handled. For time-to-event outcomes, the censoring rules and treatment of participants who did not experience an event are not reported. These omissions limit assessment of whether the reported participant counts represent complete follow-up or how uncertainty might be affected by incomplete data.

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: atrioventricular block complete (12.5%), lacunar infarction (12.5%), lower limb fracture (12.5%), overdose (12.5%), pancreatitis acute (11.1%).

For the serious adverse-event category, the registry lists 8 participants at risk and 3 affected in the 350 mg group, 18 at risk and 5 affected in the 525 mg group, and 30 at risk and 2 affected in the 700 mg group. In the other adverse-event category recorded, the corresponding entries are 8 at risk and 6 affected, 18 at risk and 9 affected, and 30 at risk and 18 affected. Listed deaths are 1, 1, and 0, respectively. These are counts, not adjusted comparisons.

The serious-event terms listed with percentages are Atrioventricular block complete and Lacunar infarction at 12.5%, Lower limb fracture and Overdose at 12.5%, Pancreatitis acute at 11.1%, and COVID-19 at 5.6%. The registry record does not specify the denominator or further context for these percentages. It also does not establish from these entries whether an event was caused by treatment.

These group counts should be interpreted cautiously because treatment allocation was non-randomized. The record does not provide event timing, exposure-adjusted rates, or details that connect the adverse-event entries to the full primary endpoint definition.

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

The record establishes that this was an extension study intended to examine continued PRO 140 monotherapy in participants who had completed the preceding study while virologically suppressed. It specifies a primary safety question based on Grade 2, 3, or 4 adverse events and treatment-emergent serious adverse events, and describes secondary outcomes related to virologic failure, re-suppression, and CD4 cell-count change.

The posted adverse-event entries offer descriptive counts by dose group, including serious-event counts, other adverse-event counts, and deaths. They do not establish that any event was caused by PRO 140, and they do not support a balanced comparison among dose groups. The non-randomized design and the lack of reported adjustment details are important limits on interpreting group differences.

The registry record does not report numerical primary-outcome analyses, estimates of uncertainty, or results for the listed virologic and CD4 outcomes. It is therefore not possible to assess the precision of the primary safety outcome or quantify the antiviral outcomes from this record. The study’s stated aims should not be mistaken for reported findings.

The registry status is terminated, but the reason for termination is not reported in the registry record. The status alone does not explain whether the study ended early, whether its objectives were met, or how termination affected follow-up. No conclusion about efficacy, safety relative to another treatment, or the cause of termination follows from the available record.

13. Why This Trial Matters Statistically

This study raises statistical questions common to long-term extension research: how to describe events during continued exposure, how to distinguish severity grading from serious-event status, and how to interpret outcomes when participants are not randomized to treatment groups. Its primary safety outcome reflects a practical focus on participant-level events over an extended treatment period, while the secondary outcomes include time-to-event and repeated-measure questions.

The design also illustrates why descriptive safety counts and comparative evidence are not interchangeable. Group counts can document what was recorded in each dose group, but a non-randomized allocation may leave group differences attributable to factors other than dose. Without an analysis plan, estimates of uncertainty, or adjustment details in the registry record, readers cannot determine how the investigators intended to address these issues.

The record’s limited reporting is itself statistically important. It defines the primary endpoint and safety population, but provides no primary analyses, no reported missing-data approach, and no multiplicity strategy. That distinction helps separate an outcome definition from an outcome result: knowing what was intended to be measured does not reveal the observed effect or its precision.

Finally, the study combines safety aims with secondary virologic and immunologic outcomes. Those outcomes require different summaries and methods, and the registry describes them without reporting analyses. A careful reading therefore keeps the stated research questions separate from the conclusions that numerical results could support.

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 trial-specific limitations constrain interpretation. The registry describes non-randomized allocation and no masking, and does not explain how participants entered the three dose groups. The groups cannot be treated as randomized, like-for-like comparisons. The record also does not describe baseline characteristics or an adjustment plan, so it is not possible to assess comparability or account for potential differences among groups.

Although the registry defines the primary safety population, it does not provide participant flow or confirm the number of people who received at least one dose. The listed enrollment is 56, while the adverse-event entries report group-specific numbers at risk; the registry does not explain the relationship between these counts and the full enrolled population. Exposure duration by group and event timing are not reported, limiting interpretation of counts over the stated follow-up period.

The primary endpoint combines graded adverse events and treatment-emergent serious adverse events, but the available adverse-event summary does not establish which entries correspond to each specific endpoint component. The record does not report endpoint-specific analyses, confidence intervals, or handling of missing data. It also does not describe the analysis populations for secondary outcomes, the censoring rules for time-to-event measures, or methods for repeated CD4 measurements.

The study is listed as terminated, with no reason reported in the registry record. That status does not by itself establish why the study ended or how termination affected outcome collection. Taken together, these gaps mean that the registry supports a description of design and recorded event counts, but not a precise or causal interpretation of treatment effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Extension Protocol for Virologically Suppressed Subjects Who Successfully Completed PRO140_CD03 Study — NCT05271370.
• Registry record last updated 2025-10-30; status last verified 2025-10.
• Results first posted 2025-10-30.
• 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

NCT05271370 is a non-randomized, unmasked, parallel extension study sponsored by CytoDyn, Inc. It enrolled 56 participants and is listed as Phase 2 and Phase 3. The study concerned virologically suppressed subjects who successfully completed PRO140 CD03 and continued weekly subcutaneous PRO 140 at 350 mg, 525 mg, or 700 mg. The registry lists the study as terminated; the reason is not reported in the registry record.

The primary outcome was the number of participants with Grade 2, 3, or 4 adverse events and the number with treatment-emergent serious adverse events, from first treatment administration to last treatment visit, up to 197 weeks. Secondary outcomes addressed virologic failure, viral re-suppression, and CD4 cell-count change. The registry defines the safety population as subjects who received at least one dose. It reports adverse-event counts by dose group, but no primary-outcome analyses or numerical results for the secondary outcomes.