A Study of Enfuvirtide (Fuzeon) in Participants With Advanced Human Immunodeficiency Virus (HIV) Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Enfuvirtide (Fuzeon) in Participants With Advanced Human Immunodeficiency Virus (HIV) Infection (NCT02582983), a na phase 4 study. The primary outcome is Number of Participants With Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a Phase 4, open-label safety trial of enfuvirtide in participants with advanced HIV infection. The registry lists a single-group model, no masking, and allocation as not applicable. All participants received enfuvirtide; the record does not describe a randomized assignment or a concurrent comparator. The registry identifies Hoffmann-La Roche as the sponsor and lists the study status as completed.

The record reports enrollment of 23 participants. The brief summary states that the target sample size was 30 individuals. These are distinct details: the enrollment count describes the participants recorded as enrolled, while the target describes the planned number stated in the summary. The record does not report why enrollment was below that target.

Eligible participants had advanced HIV-1 disease and either failed regimens containing at least one product from each antiretroviral class or experienced intolerance to earlier antiretroviral regimens. Enfuvirtide was administered at 90 mg subcutaneously twice daily. Continued treatment depended on the absence of enfuvirtide-related treatment-limiting toxicities and investigator judgment that the participant benefited from study treatment. The expected time on treatment was tied to commercial availability of enfuvirtide in Thailand.

The primary outcome was the number of participants with serious adverse events. Its observation window extended through 28 days after permanent discontinuation, described as approximately 100 weeks. The record lists a primary outcome and one additional outcome measure, but further details of the additional measure are not reported in the registry record. The record does not report a protocol, a statistical analysis plan, interim analyses, or a sample-size justification. The trial’s stated safety aim and its single-group structure are central to interpreting its results: the counts describe events among treated participants, not differences between treatment groups.

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 analysis population was defined as the number of participants who enrolled in the study and received at least one dose of study drug.

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 Number of Participants With Serious Adverse Events (SAEs), measured over Up to 28 days after permanent discontinuation of study treatment (approximately 100 weeks).

The primary endpoint counts participants who experienced at least one serious adverse event. The registry’s definition includes an event resulting in death, an event that is life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, or a congenital anomaly or birth defect. The record clarifies that “life-threatening” refers to a situation in which the participant was at risk of death at the time, not a less severe event that hypothetically might have become fatal.

A participant count is useful for describing how many people in the study had a serious event, rather than tallying multiple episodes from the same person as if they represented different participants. It offers a clinically recognizable summary of serious safety outcomes over the stated observation period. It does not, by itself, establish that treatment caused an event. Events occurring during a trial may have multiple possible explanations, and a single-group study cannot estimate how often similar events would have occurred without enfuvirtide or under another regimen.

The observation window is part of the endpoint definition: events were counted through 28 days after permanent discontinuation of study treatment, approximately 100 weeks. The analysis population is described as enrolled participants who received at least one dose. The record reports 6 participants with serious adverse events among 23 at risk. It does not report event-level timing, duration, severity grades beyond the serious-event classification, or a causal assessment for each event.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a count of participants with at least one serious adverse event, rather than a continuous measurement such as a laboratory value. For a binary outcome, each participant can be classified according to whether the event occurred during the defined observation window. The registry reports the number at risk and the number affected. In this study, the serious-event count is 6 participants among 23 at risk. This descriptive format is straightforward, but its interpretation depends on a clear event definition, an appropriate analysis population, and a specified period during which events are counted.

What does a participant count describe?

A count answers how many participants met the endpoint definition. It is not the same as a count of all individual event episodes: a participant with multiple serious events can still contribute as one participant to an endpoint defined as the number with serious adverse events. The registry does not report whether participants had multiple serious events, nor does it provide a separate total of serious event episodes. The listed count should therefore be understood as participants affected, consistent with the endpoint title.

The at-risk group is important because a count without its population context can be difficult to interpret. The record reports 23 participants at risk for serious adverse events and 6 affected. The analysis population is defined as enrolled participants who received at least one dose of study drug. The record does not describe whether any participant was excluded from the safety population after receiving a dose, or whether all participants completed the observation window.

Why does the single-group structure matter?

In a randomized comparative trial, an outcome can be contrasted between groups assigned to different interventions, subject to the trial’s design and analysis. This study had one treatment group and no comparator. Its count describes observed events among participants who received enfuvirtide, but does not show what would have happened to comparable participants under another treatment or without the study treatment. Differences attributable to disease severity, prior therapies, concomitant treatment, or other factors cannot be disentangled using a single-group count.

Open-label conduct means that masking was not used. The registry lists masking as none. In general, knowledge of treatment assignment can influence reporting, clinical assessment, and decisions about care, although serious events such as hospitalization may be more objectively verifiable than some less serious outcomes. The registry does not report procedures used to identify, adjudicate, or independently review adverse events, so those features cannot be assessed.

What can uncertainty measures add?

In general, a confidence interval expresses the range of values compatible with an estimate under a specified statistical method and its assumptions. It helps communicate how imprecisely an estimate may be measured, particularly when the number of participants is limited. No confidence interval is reported for the serious-event count in the registry record. No p-value or other inferential analysis is reported either. Consequently, the posted safety result is descriptive, and statistical precision is not quantified in the record.

In general, larger samples can provide more precise estimates of event frequency, while small samples often leave substantial uncertainty around the underlying rate. This principle does not turn the target enrollment into an observed result or a statement about statistical power. The record states a target of 30 individuals and an enrollment of 23, but does not report a sample-size justification. A planning calculation based on an observed effect would be an illustration, not observed power and not evidence about the original design unless the record documented those design assumptions.

Why can event patterns be hard to summarize?

Adverse events may recur within a participant, overlap with other events, or arise from different causes. In general, event counts and participant counts answer different questions: the former tally episodes, while the latter tally people affected. The primary endpoint is defined as a participant count. The serious-event terms are listed with percentages, but the record does not explain whether those terms are mutually exclusive, how they were grouped, or whether the percentage refers to participants or event occurrences. Those details should not be inferred from the percentages alone.

Over-dispersion is a general concern for event-count analyses when variability exceeds what a simple count model would expect; repeated events clustered within the same participant can contribute to that pattern. It is not possible to assess over-dispersion from the participant-level primary outcome alone, and the registry does not report a repeated-event model or event-level analysis. The posted endpoint does not provide the individual event histories needed to distinguish one event per participant from recurrent episodes.

The observation window also shapes the result. Counting events through 28 days after permanent discontinuation captures a specified period extending beyond treatment, described as approximately 100 weeks. In general, participants observed for different lengths of time may have unequal opportunities for events to be recorded. Time-to-event methods can account for timing and censoring when event dates and follow-up information are available, but such an analysis is not reported in the registry record. The record also does not report missing-data methods, censoring rules, or whether all participants had complete safety follow-up.

Finally, an analysis plan guides decisions about outcome definitions, populations, statistical methods, and multiplicity. The registry lists no analyses, and does not report a statistical analysis plan or interim analyses. This absence limits assessment of whether the posted outcome and analysis approach were prespecified. The appropriate reading is therefore a descriptive account of the registry’s reported safety counts, with causal and comparative conclusions left unresolved.

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("Enfuvirtide")
n      <- c(23)
events <- c(6)
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  Enfuvirtide  23  6  26.1  10.2  48.4  12.5  46.5  12.6  46.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary serious adverse event outcome and one additional outcome measure, but it does not provide details of the additional measure in the record. It lists no analyses. A statistical analysis plan, any prespecified hierarchy of outcomes, and any multiplicity adjustment are not reported in the registry record. Without that information, it is not possible to assess whether the serious-event endpoint was analyzed according to a prespecified plan or how multiple outcomes may have been handled.

Missing-data handling is not reported in the registry record. The analysis population is defined as participants who enrolled and received at least one dose of study drug, and 23 participants are listed at risk for serious adverse events. The record does not state whether safety data were missing for any participant, whether follow-up was complete, or how incomplete observation was handled. It also does not report withdrawal counts or reasons for discontinuation.

These omissions matter because the interpretation of a participant count depends on who was observed and for how long. If observation differs across participants, a simple count does not convey the amount of time each person was followed. The registry defines an observation window through 28 days after permanent discontinuation, approximately 100 weeks, but participant-specific follow-up and censoring rules are not reported. No imputation method or sensitivity analysis for missing safety information is described.

The absence of these details does not mean that data were missing or that multiplicity adjustments were necessary; it means those matters are not reported in the registry record. The posted safety counts remain descriptive, while the robustness of the analysis to missing information or multiple outcome testing cannot be assessed from the record.

12. Safety Results

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

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: cellulitis (8.7%), anaemia (4.3%), pancreatitis acute (4.3%), diarrhoea (4.3%), abdominal pain (4.3%).

The registry reports that 6 of the 23 participants at risk experienced serious adverse events. It lists 23 participants at risk and 23 affected for other adverse events. These figures describe participants in the enfuvirtide group over the study’s stated safety observation period; they are not comparisons with an untreated or alternative-treatment group.

The most frequently listed serious-event term is cellulitis at 8.7%. Anaemia, acute pancreatitis, diarrhoea, abdominal pain, and colitis are each listed at 4.3%. These are the percentages stated in the registry record. The record does not provide term-level participant counts, explain whether a participant could appear under multiple terms, or describe a causal assessment for each event. The percentages should not be read as proof that the study drug caused the events.

The death count is not reported in the registry record. Nor does the record provide event timing, duration, or participant-level follow-up. The endpoint includes events through 28 days after permanent treatment discontinuation, approximately 100 weeks. The counts are therefore best understood as a descriptive account of recorded adverse-event experience within this single-group study, rather than an estimate of comparative safety.

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

The results establish what the registry reports for this study: 6 participants with serious adverse events among 23 at risk, and 23 affected by other adverse events among 23 at risk. The serious-event terms and their listed percentages add descriptive detail about the kinds of events recorded. Together, these results document safety events among participants with advanced HIV-1 infection who received enfuvirtide in the study context.

They do not establish that enfuvirtide caused any particular event. Events can occur during treatment without being caused by treatment, and participants had advanced disease and a history of treatment failure or intolerance. The record does not report individual causality assessments. It also does not establish whether the observed event experience would be higher or lower than under another regimen, because the trial had no comparator group.

The study’s open-label, single-group design is suited to describing events observed during treatment and follow-up, but it cannot separate treatment effects from other explanations. The record does not report an inferential analysis, confidence intervals, or comparative estimates. As a result, the precision of the event frequency is not quantified through those methods in the posted results. The small enrollment and the fact that the target was 30 while enrollment was 23 further underscore that the counts describe this study group rather than a definitive estimate for a broader population. The reason enrollment did not reach the stated target is not reported in the registry record.

These data also do not answer questions about antiviral efficacy, changes in HIV measures, or whether participants benefited from treatment. The primary outcome is a safety count, and the registry record does not report results for efficacy outcomes in the information. The investigator’s judgment about continuing treatment is described in the study summary, but no result establishing benefit is reported.

The most appropriate conclusion is limited: the registry records serious and other adverse events among treated participants over the specified observation period. Determining causation, comparing safety with other regimens, or extending the findings to different patient groups would require evidence beyond these single-group counts.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it shows the difference between describing safety experience and estimating a treatment effect. A participant count can summarize how many people experienced an outcome in a study group. Without a comparison group, however, it cannot reveal whether that count reflects a treatment-related change or the risks associated with the underlying illness, prior therapies, other care, or chance variation.

The endpoint is also a reminder that outcome definition and observation period shape interpretation. Serious adverse events were defined by specified consequences, and the observation window extended to 28 days after permanent discontinuation, approximately 100 weeks. The meaning of the count depends on those definitions and on who contributed safety data. The registry defines the analysis population but does not report participant-specific follow-up or missing-data handling.

Enrollment and planning should also be distinguished. The record reports 23 enrolled participants and a target of 30 individuals. The target is not an observed result, a power calculation, or a guarantee of precision. The record does not report the rationale for the target or why enrollment was lower. This separation is important whenever a planned enrollment figure and a realized study population appear together.

Finally, the record illustrates why a safety count should not be overinterpreted as a causal finding. The event terms and percentages are informative as descriptions of what was recorded, but the single-group design and absence of reported inferential analyses leave comparative uncertainty unresolved. The statistical lesson is not that the count is uninformative; it is that its scope is descriptive and should remain aligned with the design and reporting detail.

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 principal design limitation is the absence of a control group. Because all participants received enfuvirtide, the registry’s safety counts cannot estimate a difference relative to another treatment or to no study treatment. The open-label design also means treatment was not masked. The record does not describe independent event adjudication or other procedures that might reduce the influence of knowledge of treatment.

The study enrolled 23 participants, while the brief summary states a target sample size of 30 individuals. The record does not report why enrollment was below target or whether that affected the planned analyses. A sample-size justification is not reported in the registry record. The results therefore need to be read as counts from the enrolled group, not as evidence that a prespecified precision goal was met.

The participant group was specific: advanced HIV-1 infection and prior treatment failure across antiretroviral classes or intolerance to previous regimens. These features limit direct generalization to people with different disease status or treatment histories. The record does not provide further demographic or clinical characteristics in the information.

Several details needed for fuller safety interpretation are not reported in the registry record, including event timing, event-level causality judgments, whether participants had multiple serious events, follow-up completeness, missing-data methods, and participant-specific observation time. The death count is also not reported. Term-level percentages are listed without accompanying counts or an explanation of whether terms overlap.

The record does not report a statistical analysis plan, confidence intervals, hypothesis tests, interim analyses, or a multiplicity approach. Efficacy results are not reported in the information. These gaps do not negate the descriptive safety counts, but they limit assessment of precision, causal attribution, completeness, and comparative meaning.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Enfuvirtide (Fuzeon) in Participants With Advanced Human Immunodeficiency Virus (HIV) Infection — NCT02582983.
• Registry record last updated 2016-07-06; status last verified 2016-05.
• Results first posted 2016-07-06.
• 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

The registry record describes a completed Phase 4, open-label, single-group safety study of enfuvirtide in participants with advanced HIV-1 infection. It lists Hoffmann-La Roche as sponsor, enrollment of 23 participants, and a target sample size of 30 individuals. Participants received enfuvirtide 90 mg subcutaneously twice daily.

The primary outcome was the number of participants with serious adverse events through 28 days after permanent discontinuation of study treatment, approximately 100 weeks. The record reports 6 participants with serious adverse events among 23 at risk. It also reports 23 participants affected by other adverse events among 23 at risk, with several serious-event terms listed by percentage.

Because there was no comparator, the results are descriptive and do not estimate a relative treatment effect or establish causation. A statistical analysis plan, inferential results, missing-data methods, and several event-level details are not reported in the registry record.