Study in Hepatitis C Virus (HCV) Infected Patients Undergoing Liver Transplantation to Evaluate a Human Monoclonal Antibody Against Hepatitis C: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study in Hepatitis C Virus (HCV) Infected Patients Undergoing Liver Transplantation to Evaluate a Human Monoclonal Antibody Against Hepatitis C (NCT01121185), a randomized phase 2 study. The primary outcome is Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation.

2. Clinical Question

The clinical question combines a virologic outcome with a specific post-transplant time point. Detectable serum HCV RNA indicates that the assay found measurable viral RNA in the blood sample; the endpoint is not a measure of symptom burden, graft function, or the amount of virus over the entire follow-up period. The registry also names secondary outcomes concerning adverse events, changes in serum HCV RNA at other time points, histologic evidence of hepatitis, graft function, and time to recurrence of detectable HCV RNA. Those outcomes address different aspects of follow-up and should not be treated as interchangeable with the Day 42 primary endpoint.

3. Trial Design

The registry describes NCT01121185 as a phase II randomized, double-blind, placebo-controlled, parallel-group study. Its official title identifies the intervention as MBL-HCV1, a human monoclonal antibody against HCV E2 glycoprotein. The sponsor is MassBiologics. The registry lists the conditions as HCV infection and liver transplantation.

The experimental arm received MBL-HCV1, while the placebo comparator was 0.9% sodium chloride. The masking designation is quadruple. The record does not identify which specific roles were masked, describe the randomization procedure, or state the allocation ratio. The reported arm sizes for the primary endpoint were 6 for MBL-HCV1 and 5 for placebo. These are the numbers attached to the endpoint results, not a description of the full enrollment flow.

Enrollment is listed as 13. The primary endpoint analysis population is described as the eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation. The registry lists the study status as terminated, with a start date of 2010-06 and primary completion in 2011-06. The reason for termination is not reported in the registry record, and the status alone does not establish why the study ended.

The registry lists seven secondary outcomes, including safety, HCV RNA measures at several post-transplant time points, a histologic assessment at baseline and Day 42, graft function measures, and time to detectable HCV RNA recurrence. It also lists nine outcome measures and zero analyses. The record does not report details of treatment dosing, follow-up schedules beyond the listed outcome time points, the planned statistical model, or a protocol-based sample-size justification. Those omissions limit how fully the study procedures and analysis choices can be reconstructed.

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.

Before assignment: Reasons for exclusion after randomization included identification of a protocol-specified exclusion criterion in the recipient or the donor at the time of organ offer or failure to undergo liver transplantation.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

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 eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation, measured over At Day 42 post-transplantation.

The primary endpoint is the proportion of participants with detectable serum HCV RNA at Day 42 post-transplantation. Serum HCV RNA was measured by quantitative RT-PCR. The endpoint is binary at the participant level: each participant is classified according to whether HCV RNA was detectable at the specified time point, and the result is expressed as a percentage of participants.

A fixed time point makes it possible to describe virologic status at a defined stage after transplantation. A binary endpoint can be readily interpreted as the frequency of detectable virus in each study arm, but it does not show the measured viral RNA concentration or its trajectory. The registry separately lists change in serum HCV RNA between baseline and Day 3, 14, 28, and 42 post-transplantation, as well as time to onset of recurrence of detectable HCV RNA. Those outcomes capture different information from the primary Day 42 proportion.

Both arms have a posted primary endpoint result of 100.0%. The record does not report confidence intervals or a statistical test for this comparison. It also does not provide assay detection thresholds or further details about handling measurements at or near those thresholds. Consequently, the reported endpoint supports a description of the observed proportions, but offers limited information about the precision of those proportions or about variation in viral RNA levels.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary percentage: the proportion of participants with detectable serum HCV RNA at Day 42 post-transplantation. The registry identifies quantitative RT-PCR as the measurement method. In general, a binary endpoint reduces each participant's measurement at the defined time point to one of two categories, such as detectable or not detectable. This is different from analyzing the actual RNA concentration, and different from analyzing the time until detection.

What does the percentage describe?

A percentage describes the observed frequency of an outcome in a group. For this study, the posted percentages are 100.0% for MBL-HCV1 and 100.0% for placebo. They are descriptive summaries of the endpoint observations. The registry reports endpoint group sizes of 6 and 5, but provides no confidence intervals for the percentages. In general, a percentage alone does not show how uncertain the estimate may be, especially when based on a small group.

What would a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity, such as a proportion or a difference between proportions. It helps distinguish a precise estimate from one that is compatible with a wide range of values. No confidence interval is reported for the primary endpoint, so the precision of either arm's percentage and the precision of any between-arm difference are not documented in the registry record. A confidence interval would not by itself prove that a treatment effect is absent or present; it would describe uncertainty under the statistical method used to calculate it.

Why is there no reported two-arm comparison?

The registry indicates that values were missing or not estimable for a two-arm comparison for this binary percentage endpoint. Thus, the posted record gives the arm-specific percentages but not a comparison statistic or p-value. A comparison of binary outcomes can be assessed with different methods, and the choice can depend on the planned analysis and the data structure. The registry does not report which method was planned or why a comparison could not be estimated. No method should be inferred from the outcome type alone.

Why do the group sizes matter?

In general, estimates from limited groups are less stable than estimates based on larger groups: a change in one participant's classification can shift a proportion more noticeably. This is a general property of percentage estimates, not a new calculation about this trial. The group sizes reported with the primary endpoint are 6 and 5. The registry enrollment is 13, while the primary analysis population is described as the eleven subjects who were randomized, initiated study infusions, and underwent transplantation. These figures refer to different stages or populations and should not be substituted for one another.

How should planning illustrations be understood?

In general, a sample-size calculation estimates how many participants might be needed under stated assumptions to detect a specified effect with a chosen statistical power and significance level. Such a calculation is a planning illustration, not an observed result and not evidence that a completed study had a particular probability of detecting an effect. The registry's stated assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Time-to-event planning calculations use total events, whereas other planning calculations use participants per arm. The record does not report that these assumptions were the trial's original design assumptions, and the registry does not give a protocol-based sample-size justification.

Because a two-arm calculation is not estimable for this binary endpoint in the posted results, a planning illustration based on an observed effect should not be treated as a definitive design recommendation. In general, estimates used for planning can be unstable when the observed effect comes from a small study. Planning values also depend on assumptions about the effect size, statistical method, significance level, allocation, and outcome variability. They do not change the interpretation of the observed Day 42 percentages.

What does over-dispersion mean in general?

Over-dispersion is a general statistical issue in which observed variability is greater than a model assumes. It can make standard errors too small if the model does not account for the extra variability, which in turn can make confidence intervals too narrow or tests too optimistic. Over-dispersion is not reported as an issue in this registry record. For the binary Day 42 endpoint, the record does not identify a model or report model-based uncertainty, so there is no basis to say that over-dispersion was assessed or present.

The registry lists multiple secondary outcomes, but does not report a statistical analysis plan or analyses. A statistical analysis plan would ordinarily clarify which outcomes were primary, which comparisons were intended, how missing observations would be treated, and whether adjustment for multiple testing was planned. Those details are not reported in the registry record. The appropriate reading is consequently descriptive and limited to the outcome values and population statements that are posted.

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("Experimental: MBL-HCV1", "Placebo Comparator: 0.9% Sodium Chloride")
n      <- c(6, 5)
events <- c(6, 5)
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  Experimental: MBL-HCV1  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Placebo Comparator: 0.9% Sodium Chloride  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and seven secondary outcomes. The secondary outcomes cover adverse events, HCV RNA changes at several time points, histologic evidence of hepatitis, graft function measures, and time to recurrence of detectable HCV RNA. Considering several outcomes or time points can raise a multiplicity issue: in general, the chance of finding at least one apparently notable result can increase when many comparisons are tested. Whether and how to adjust for this depends on the prespecified analysis plan. That plan, including any multiplicity strategy, is not reported in the registry record.

The record lists zero analyses. It does not report a statistical test for the primary endpoint, a confidence interval, or an inferential analysis of the secondary outcomes. It is therefore not possible to determine from the registry whether any analysis was planned but not posted, whether the listed outcomes were all intended for formal testing, or whether multiplicity adjustment was considered.

The primary endpoint population is explicitly described as the eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation. The endpoint arm sizes are 6 for MBL-HCV1 and 5 for placebo. How participants outside that population were handled, and whether any endpoint observations were missing, are not reported in the registry record. The record also does not describe imputation, censoring rules for the primary binary outcome, or sensitivity analyses.

In general, the analysis population and missing-data rules matter because they define which observations contribute to an estimate and how incomplete measurements are treated. The available information supports describing the specified primary population and its posted results, but not reconstructing an intention-to-treat analysis or other population that is not stated.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hepatitis c (40.0%), abdominal pain lower (20.0%), vomiting (20.0%), clostridium difficile colitis (20.0%), post procedural haemorrhage (20.0%).

The registry reports serious adverse event counts by arm: 1 of 6 in the MBL-HCV1 group and 4 of 5 in the placebo group. It also reports other adverse event counts of 6 of 6 and 5 of 5, respectively. These are the recorded counts and group denominators; they should not be confused with the primary virologic endpoint or interpreted as a statistical comparison. The record does not provide a comparative analysis of these safety figures.

The listed serious adverse event terms include Hepatitis C at 40.0%, and Abdominal Pain Lower, Vomiting, Clostridium Difficile Colitis, Post Procedural Haemorrhage, and Blood Creatinine Increased at 20.0% each. The registry does not specify in this listing which treatment arm each term refers to, so those percentages should not be assigned to an arm. The listed terms are event categories, not proof that the study treatment caused them.

Deaths are not reported in the registry record. The safety results should be read as descriptive registry counts, with limited information about event attribution, timing, severity detail beyond the serious-event designation, or comparative uncertainty. The registry identifies adverse events and treatment-emergent adverse events as a secondary outcome assessed through medical history, physical examination, and laboratory evaluation, but does not provide a detailed safety analysis plan.

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

The result establishes a narrow descriptive fact: the registry reports detectable serum HCV RNA at Day 42 post-transplantation in 100.0% of participants in each arm. The primary outcome was measured by quantitative RT-PCR, and the stated analysis population consisted of the eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation. The record does not report a confidence interval or statistical test for the arm comparison.

The result does not establish equivalence between MBL-HCV1 and placebo. Equal observed percentages do not demonstrate that all underlying outcome probabilities are equal, and without uncertainty estimates the range of plausible differences cannot be judged from the posted record. The result also does not establish that the intervention had no effect on viral RNA amount, on the timing of recurrence, or on outcomes at other time points. Those questions are not answered by a single binary endpoint measured at Day 42.

The brief summary describes aims concerning prevention, delay, and reduction of detectable HCV after transplantation. These aims extend beyond the specific primary endpoint result. The registry lists secondary outcomes that address RNA changes, recurrence, histology, graft function, and safety, but lists zero analyses. Consequently, the primary result should not be treated as a complete account of the study's broader clinical questions.

The posted results also do not explain why the study was terminated. Termination status does not, on its own, establish a safety concern, a lack of efficacy, recruitment difficulty, or any other particular explanation. No reason for termination is reported in the registry record.

More generally, a descriptive proportion and a treatment-effect conclusion are not the same thing. A treatment-effect conclusion requires a comparison interpreted with an appropriate analysis and its uncertainty, alongside the study design and limitations. Here, the central registered result is the same observed Day 42 proportion in both arms, with no reported inferential comparison. It is appropriate to report that finding precisely and avoid turning it into a claim that the treatments are interchangeable or that a clinical benefit or harm has been established.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between an observed endpoint percentage and an estimate that supports a comparative conclusion. The primary result is easy to state: 100.0% in each arm had detectable serum HCV RNA at Day 42 post-transplantation. Yet the registry does not report an uncertainty interval or a statistical comparison. The apparent simplicity of matching percentages should not obscure how much information is needed to assess precision and comparative effects.

The record also illustrates why the analysis population must be stated alongside an outcome. Enrollment is listed as 13, whereas the primary endpoint population is described as the eleven randomized subjects who initiated study infusions and underwent transplantation. The endpoint groups are reported separately as 6 and 5. These numbers describe different aspects of the record; they cannot be collapsed into a single undifferentiated sample description.

There is a second important distinction between a fixed-time binary outcome and longitudinal or time-to-event outcomes. Detectable HCV RNA at Day 42 does not describe the amount of RNA over time or the timing of recurrence. The registry lists separate outcomes for RNA changes and recurrence, reflecting that these questions require different summaries and analyses.

Finally, a terminated study with a small reported endpoint population may leave substantial uncertainty, but the status and group sizes do not reveal the reason for termination or the original design rationale. The record does not report a statistical plan, sample-size justification, or analyses. Recognizing these absences is statistically important: it prevents a descriptive finding from being overextended into a conclusion the posted analysis cannot support.

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 limitation of the posted primary result is the absence of an inferential comparison. Although the arm-specific percentages are reported, confidence intervals and a test statistic are not. The registry notes that a two-arm comparison for the binary percentage endpoint was missing or not estimable. As a result, the precision of the percentages and the uncertainty around any between-arm difference are not available.

The primary endpoint groups are small, with reported sizes of 6 and 5. In general, small groups provide limited precision for estimating proportions, and the outcome of an individual participant can have a noticeable influence on a percentage. This general consideration is not a recalculation of the study's uncertainty; the registry does not report an interval estimate.

The record's enrollment figure, endpoint population, and arm-specific numbers refer to different descriptions. The reason that the primary endpoint population is narrower than enrollment is not reported in the registry record, beyond the stated inclusion criteria for that population. Further participant flow, missing endpoint data, and handling of participants not included in the primary analysis are not reported.

The trial status is terminated, but the reason is not reported. The registry lists secondary outcomes but no analyses, and does not report a detailed statistical analysis plan, multiplicity approach, treatment dosing information, or protocol-based sample-size justification. The exact methods for any unposted analyses cannot be inferred.

The safety listing is also limited: serious adverse event counts are given by arm, while the displayed serious-event term percentages are not assigned to specific arms in the record. Deaths are not reported in the registry record. These limitations restrict interpretation of both comparative safety and the broader secondary outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study in Hepatitis C Virus (HCV) Infected Patients Undergoing Liver Transplantation to Evaluate a Human Monoclonal Antibody Against Hepatitis C — NCT01121185.
• Registry record last updated 2016-06-14; status last verified 2016-03.
• Results first posted 2016-06-14.
• 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

NCT01121185 is a phase II randomized, double-blind, placebo-controlled, parallel-group study of MBL-HCV1 in patients with HCV infection undergoing liver transplantation. The comparator was 0.9% sodium chloride placebo, and the masking designation was quadruple. MassBiologics is listed as the sponsor. Enrollment is 13; the study status is terminated, with a start date of 2010-06 and primary completion in 2011-06.

The primary endpoint was the proportion with detectable serum HCV RNA at Day 42 post-transplantation, measured by quantitative RT-PCR. The specified analysis population comprised the eleven randomized subjects who initiated study infusions and underwent transplantation. The posted proportions were 100.0% in the MBL-HCV1 arm and 100.0% in the placebo arm. No statistical comparison or confidence interval is reported.

The registry lists seven secondary outcomes and zero analyses. The reason for termination, statistical analysis plan, and handling of missing endpoint data are not reported in the registry record.