Study to Assess Adverse Events, Change in Disease Activity and How Oral ABBV-4083 Capsules When Given Alone or In Combination With Albendazole Capsules Moves in The Body of Adult Participants With Onchocerca Volvulus Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Adverse Events, Change in Disease Activity and How Oral ABBV-4083 Capsules When Given Alone or In Combination With Albendazole Capsules Moves in The Body of Adult Participants With Onchocerca Volvulus Infection (NCT04913610), a randomized phase 2 study. The primary outcome is Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules.

2. Clinical Question

The trial was a randomized, quadruple-masked, parallel-group Phase II study. Its brief summary describes a study conducted in two parts, with Part 1 intended to explore dose and treatment combinations and Part 2 to assess selected regimens. The posted primary-endpoint results concern Part 1. Although the record describes plans for Part 2, Part 2 primary results are not reported in the registry record. The central statistical question is therefore narrower than whether a complete treatment strategy has been established: it is how the Month 6 worm-level endpoint was distributed across the reported Part 1 regimens, and how much uncertainty surrounds each estimate.

3. Trial Design

The registry identifies this as a Phase II randomized, quadruple-masked, parallel-group trial of ABBV-4083 for onchocerciasis. Enrollment is recorded as 153, and the trial status is terminated. The brief summary describes two parts: Part 1 compared treatment combinations and schedules, while Part 2 was intended to evaluate selected doses and included a later ivermectin or matching-placebo treatment. The registry record does not report Part 2 results in the posted outcome data.

Five Part 1 treatment arms appear in the primary endpoint results. The control arm received albendazole 400 mg with ABBV-4083 placebo for 7 days, followed by ABBV-4083 placebo for 7 days. The other arms used ABBV-4083 400 mg with albendazole placebo for 7 days, with either placebo or active ABBV-4083 in the next 7 days; ABBV-4083 400 mg with albendazole 400 mg for 7 days followed by ABBV-4083 placebo; or a sequence of both active drugs for 3 days, ABBV-4083 with albendazole placebo for 4 days, and ABBV-4083 placebo for 7 days. These are distinct treatment schedules, not interchangeable versions of one exposure.

The primary outcome was assessed at Month 6 after nodulectomy. Its specified analysis population was per protocol and required a Month 6 nodulectomy with live female adult worms, treatment completion, and no use of prohibited medication. That population is more restricted than all randomized participants. The outcome-specific group sizes range from 20 to 23. The registry record does not report the reasons that participants were absent from this endpoint population, nor does it describe a missing-data method.

The recorded enrollment and the enrollment figures discussed as approximate plans in the brief summary differ. The registry record does not explain that difference or report why the trial was terminated. These registry entries matter when interpreting the scope of the posted evidence: the estimates relate to the observed endpoint populations and schedules, and should not be treated as a complete account of every planned trial component.

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: A total of 153 participants were randomized, of which 151 received study drug (Intention-to-Treat, ITT; Safety population).

Randomized Participants

Reasons for not completing this period:

Treated (ITT & Safety Population)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol population: all ITT participants who had nodulectomy at Month 6 (ND6M) with live female adult worms, who completed treatment, and who did not take prohibited medication(s) during the 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: Intention-to-Treat (ITT) population includes all randomized participants who received at least one dose of study drug

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules, measured over At Month 6.

The primary endpoint is the percentage of live female adult worms without Wolbachia at Month 6. Wolbachia status was determined by immunohistology of nodules collected after nodulectomy. In practical terms, the endpoint describes the proportion of assessed live female worms in a participant’s nodules that met the stated absence-of-Wolbachia classification. It is not a direct count of all worms in the body and is not itself a measure of symptoms, disability, or overall clinical status.

This type of biological endpoint can be useful in an early proof-of-concept trial because it measures a parasite-related feature under study. However, its interpretation depends on which participants contribute evaluable nodules and which worms are classified as live and female. The registry’s per-protocol definition further limits the endpoint population to participants who completed treatment, had the specified Month 6 procedure and findings, and did not take prohibited medication. The estimates therefore describe that defined group, not necessarily every randomized participant.

For each arm, the registry reports a percentage and a 95% confidence interval. The control estimate was 6.0% (95% CI 2.6 to 13.2). Estimates in the other arms were 2.3% (95% CI 0.6 to 8.0), 0.0% (95% CI 0.0 to 4.5), 0.0% (95% CI 0.0 to 4.1), and 2.6% (95% CI 0.7 to 9.0). A confidence interval expresses uncertainty around an estimate; it does not show the range of individual participant results. No formal primary comparison or associated p-value is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports descriptive arm-level primary endpoint results: a percentage and a 95% confidence interval for each treatment group. The primary endpoint is a count-based outcome expressed as a percentage, but the registry does not post a formal comparison test, an effect estimate contrasting an active schedule with control, or a p-value for the primary outcome. This distinction matters: descriptive estimates show what was observed in each group, while a comparative analysis quantifies a specified contrast and its uncertainty.

What does a confidence interval convey?

A confidence interval summarizes uncertainty in an estimate under the statistical method used to construct it. A narrower interval indicates greater precision than a wider interval, all else equal. It is not a range containing a fixed proportion of individual worms or participants, and it does not mean there is a stated probability that the true value lies inside the particular interval. The primary endpoint intervals are broad enough to show that the point estimates should not be treated as exact. The zero estimates are accompanied by intervals extending above zero, so zero observed in the reported sample is not equivalent to certainty of zero beyond that sample.

Comparing separate confidence intervals is not a substitute for a direct statistical test of a treatment contrast. Overlap between intervals does not settle whether a contrast is compatible with no difference; a contrast needs its own estimate and uncertainty. For the primary endpoint, that direct comparative analysis is not reported in the registry record. No primary p-value or formal comparison should be inferred from the arm-specific intervals.

How should the secondary tests be read?

For two continuous secondary outcomes, the registry reports Mann-Whitney U tests for comparisons involving the control and two treatment arms. This rank-based test evaluates differences in the distributions of observations; it is not automatically a test of the difference in arithmetic means. The registry’s descriptive values for these outcomes are means and standard deviations, while the reported analysis is rank-based. A mean difference calculated from those summaries is therefore not the same estimand as the Mann-Whitney test result.

For the binary secondary outcome concerning participants without microfilariae in nodular tissue, the registry reports chi-square tests for comparisons involving the control and two treatment arms. A chi-square test assesses whether the observed category distributions differ under its assumptions. The record gives p-values for these analyses, but does not report a multiplicity adjustment. The p-values should be treated as unadjusted findings rather than as a family-wise confirmatory analysis. The registry record does not report whether other secondary endpoints had formal tests, or how any such tests were handled.

The posted results also include simple, unadjusted re-calculations for selected secondary continuous and binary contrasts. These are calculations from posted summary statistics, not the sponsor’s complete analysis. The registry record does not report a discrepancy between those calculations and the reported analyses. Even so, the reported analysis method and its target question remain important: a recalculated difference in means or proportions need not reproduce a rank-based or chi-square test.

What are the planning illustrations?

The sample-size illustrations are based on observed effects and specified assumptions: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They show hypothetical participants per arm for stated fractions of an observed effect. They are planning illustrations, not observed power and not evidence about the probability that the trial detected a real effect. They are also not the trial’s original sample-size justification. That justification is not reported in the registry record.

More generally, a planning calculation depends on the assumed effect, variability, analysis method, and design assumptions. If the observed effect is unstable or imprecise, calculations built from it may also be unstable. These illustrations should not be read as proof that a larger study would reproduce the observed effect, nor as evidence that the original trial was designed around these calculations. The record does not report an interim-analysis plan, stopping boundaries, or the full statistical analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry record reports multiple secondary outcomes, several treatment groups, and selected pairwise analyses. It does not report a multiplicity adjustment or a hierarchy of hypotheses that would distinguish confirmatory outcomes from exploratory ones. Without that information, the reported secondary p-values should be read as unadjusted. Considering many tests together makes isolated nominal results less persuasive than a prespecified, multiplicity-controlled analysis.

The record also does not report a complete missing-data strategy. It does not state how missing endpoint measurements were handled, whether any imputation was used, or whether sensitivity analyses assessed the effect of missing observations. The primary endpoint population is explicitly per protocol and requires treatment completion, a Month 6 nodulectomy with live female adult worms, and no prohibited medication use. This makes the estimand narrower than an analysis of all randomized participants. The registry record does not report a primary intention-to-treat result alongside it.

Different outcome measures have different reported group sizes, which means their analyses do not necessarily represent the same participants. The record does not explain all reasons for these differences. It also does not report how missingness might relate to treatment, endpoint status, or follow-up. Those omissions limit assessment of whether the analyzed participants represent the original randomized groups.

The registry does not report the sample-size justification, a full statistical analysis plan, interim analyses, or decision rules for early stopping. Nor does it explain the trial’s terminated status. These details are relevant to understanding whether analyses were prespecified and how the study’s conduct may have shaped the available results. Their absence does not demonstrate that a particular procedure was or was not used; it means the relevant information is not reported in the registry record.

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: myocardial ischaemia (3.3%), retinal vein occlusion (3.3%), electrocardiogram t wave inversion (3.3%), anaemia (3.2%), atrioventricular block second degree (3.2%).

The posted safety counts distinguish serious adverse events from other adverse events. In the four ABBV-4083 arms, serious events were reported in 0 of 31, 2 of 31, 2 of 30, and 0 of 30 participants, respectively. In the albendazole-only control arm, serious events were reported in 4 of 31 participants. A pooled ABBV-4083 grouping reports 4 serious events among 122 participants at risk. The registry records zero deaths in each listed group.

These are counts of participants affected as recorded in the safety data; they do not by themselves establish whether an event was caused by a study drug. The record also lists other adverse events affecting participants in each arm, but an adverse event count should not be treated as a severity measure equivalent to a serious adverse event count. The listed serious-event terms include myocardial ischaemia, retinal vein occlusion, electrocardiogram T wave inversion, anaemia, second-degree atrioventricular block, and retinal haemorrhage. The registry does not provide enough information in these summary counts to attribute an individual event to a particular treatment.

Safety comparisons are descriptive. The record does not report a formal statistical comparison of adverse-event rates, an adjusted analysis, or detailed follow-up for each event. The counts therefore summarize what was recorded in the listed groups, not a definitive comparative safety conclusion.

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

The primary endpoint results show the observed percentage of live female adult worms without Wolbachia in the defined Month 6 per-protocol population for each Part 1 schedule. They also show uncertainty around each arm-level estimate through 95% confidence intervals. These findings describe a biological endpoint assessed from nodules; they are not direct measurements of symptoms, disability, or economic productivity.

The results do not establish that one regimen is superior to another. The registry record does not report a formal primary comparison, a primary p-value, or a prespecified threshold for interpreting a difference. The arm-level estimates and their intervals should not be converted into an unreported comparative conclusion. A zero point estimate in an arm also does not establish that the underlying percentage is exactly zero.

The endpoint analysis applies to a selected per-protocol population rather than automatically to every randomized participant. The registry does not report a corresponding intention-to-treat primary analysis or a missing-data sensitivity analysis. The secondary outcomes offer additional biological observations, but they involve different measures and selected unadjusted tests; they do not resolve these limitations or supply a single overall treatment effect.

The record identifies the study as terminated but does not report the reason. Its status alone does not indicate whether termination was related to efficacy, safety, recruitment, or another cause. Nor does the registry record describe the full statistical plan, original sample-size justification, or interim analyses. Those absences restrict what can be concluded about the design and conduct.

Accordingly, the posted results are best understood as descriptive and exploratory evidence from Part 1 of a Phase II trial. They can inform statistical questions and the design of further research, but they do not establish a clinical benefit or lack of benefit, and they do not support medical advice.

13. Why This Trial Matters Statistically

This trial illustrates why endpoint definition and analysis population matter in biostatistics. The primary outcome is a worm-level biological measure, while its analysis population is defined through participant-level eligibility for the Month 6 assessment. Those two levels of measurement need to be kept distinct: the percentage summarizes worm classifications, whereas the reported group sizes count participants contributing to the endpoint.

It also illustrates the difference between arm-specific estimates and a treatment comparison. Percentages and confidence intervals describe each group, but a causal or comparative claim requires a specified contrast and an appropriate analysis. The registry reports the primary endpoint descriptively, without a primary contrast test. That absence is consequential: visual comparison of point estimates cannot replace an inferential analysis that accounts for uncertainty and the chosen estimand.

The trial has several treatment schedules, related secondary outcomes, and an exploratory Phase II purpose. This creates a setting in which multiplicity and outcome selection deserve attention. When multiple endpoints and comparisons are examined, isolated findings can be misleading unless the analysis plan clarifies which questions are primary and how error rates are managed. Those details are not reported in the registry record.

Finally, the terminated status and difference between recorded enrollment and enrollment plans described in the brief summary illustrate why registry metadata and outcome results should be read together. The record gives useful information about the design, analysis populations, and observations, while leaving important questions about termination, missing data, and prespecification unanswered. Statistical interpretation requires acknowledging both the data and those reporting limits.

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.

The primary endpoint analysis is restricted to a per-protocol population with a Month 6 nodulectomy and live female adult worms. Participants who did not meet those requirements are not represented in the endpoint estimates. The registry record does not report a primary intention-to-treat analysis, the full reasons for non-inclusion, or sensitivity analyses addressing missing outcomes.

Each arm’s primary endpoint group size is small, and the confidence intervals indicate uncertainty around the percentages. The registry gives arm-specific results but no direct primary treatment contrasts or p-values. It is therefore not possible to assess the primary endpoint through a posted formal comparison among schedules. The result also depends on an immunohistology assessment of worms in nodules, rather than a whole-body measure or a direct clinical outcome.

The study included multiple schedules and secondary endpoints. The registry reports only selected secondary tests, without a reported multiplicity strategy or analysis hierarchy. The secondary findings should consequently be viewed as exploratory, and the record does not support a single integrated interpretation across the biological measures.

The study is marked terminated, but the reason is not reported in the registry record. The brief summary describes a planned enrollment that differs from the recorded enrollment, and the record does not explain the difference. Part 2 is described in the study summary, but Part 2 results are not reported among the outcomes. The full statistical analysis plan, sample-size justification, interim-analysis approach, and missing-data procedures are also not reported. These limitations constrain assessment of prespecification, representativeness, and the completeness of the trial’s reported evidence.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Assess Adverse Events, Change in Disease Activity and How Oral ABBV-4083 Capsules When Given Alone or In Combination With Albendazole Capsules Moves in The Body of Adult Participants With Onchocerca Volvulus Infection — NCT04913610.
• Registry record last updated 2024-09-19; status last verified 2024-08.
• Results first posted 2024-09-19.
• 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

The registry describes a randomized, quadruple-masked, parallel-group Phase II study of ABBV-4083 regimens for onchocerciasis. Recorded enrollment is 153, and the trial status is terminated. The posted primary outcome is the Part 1 percentage of live female adult worms without Wolbachia at Month 6, assessed by immunohistology of nodules. Results are reported by arm for a per-protocol population, with 95% confidence intervals.

The primary estimates range from 0.0% to 6.0%. The registry record does not report a formal primary comparison or explain the termination. Secondary outcomes cover additional worm and microfilariae measures, with selected unadjusted analyses. The record does not report the multiplicity plan, missing-data methods, full statistical analysis plan, or original sample-size justification. The posted findings are therefore descriptive and exploratory, with important limits on comparative interpretation.