This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of TB31F (NCT04238689), a non-randomized phase 1 study. The primary outcome is Number and Severity of Adverse Events After TB31F Administration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04238689 |
| Phase | Phase 1 |
| Condition | Malaria,Falciparum |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Radboud University Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
Healthy, malaria-naïve adults in the Netherlands. The registry lists an enrollment of 25 and describes five sequential groups, each with five participants.
Intervention
Monoclonal antibody TB31F, administered intravenously at 0.1 mg/kg, 1 mg/kg, 3 mg/kg, or 10 mg/kg, or subcutaneously at 100mg. The study description says doses were escalated across groups.
Comparator
There is no randomized control group. The groups received different doses or routes in a non-randomized, sequential design, so they are not like-for-like comparison groups.
Primary question
What numbers and severities of solicited local and general adverse events, clinically significant laboratory abnormalities, unsolicited adverse events, and serious adverse events were recorded after TB31F administration? The registry also lists serum concentration and functional transmission-reducing activity as secondary outcomes.
3. Trial Design
This is a completed phase 1 study of TB31F, a monoclonal antibody, in healthy malaria-naïve adults in the Netherlands. The registry identifies Radboud University Medical Center as sponsor and lists the trial as non-randomized, unmasked, and sequential. The enrollment listed in the registry is 25.
The five groups are described as receiving escalating doses. Groups 1 through 4 received TB31F intravenously at 0.1 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg, respectively. Group 5 received 100mg subcutaneously. Each group description specifies five participants. The descriptions also state that administration was staggered, with observation for adverse events before subsequent volunteers received their dose. The minimum interval between administrations is specified for Group 1; the remaining group descriptions are truncated in the registry record, so their full administration details are not reported in the registry record.
The primary outcome concerns numbers and severities of adverse events and clinically significant laboratory abnormalities. Its timeframes vary by event category: solicited local events are followed from day 0 to day 7; solicited general events and clinically significant laboratory abnormalities from day 0 to day 28; and unsolicited events and serious adverse events from day 0 to day 84. Serum concentration and functional transmission-reducing activity are listed as secondary outcomes.
The sequential design is relevant to interpretation. These groups were not randomized to competing treatments, and they differ in dose or route. Their results describe the observations within each group; they do not provide a controlled estimate of a dose or route effect.
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
| Stage | Group 1 - 0,1mg/kg TB31F | Group 2 - 1mg/kg TB31F | Group 3 - 3mg/kg TB31F | Group 4 - 10mg/kg TB31F | Group 5 - 100mg TB31F |
|---|---|---|---|---|---|
| STARTED | 5 | 5 | 5 | 5 | 5 |
| COMPLETED | 5 | 5 | 5 | 5 | 5 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Number of volunteers that experienced a grade 1, 2 or 3 local solicited, general solicited, unsolicited or laboratory adverse event per group.
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.
| Characteristic | Unit | Group 1 - 0,1mg/kg TB31F | Group 2 - 1mg/kg TB31F | Group 3 - 3mg/kg TB31F | Group 4 - 10mg/kg TB31F | Group 5 - 100mg TB31F | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 5 | 5 | 5 | 5 | 5 | 25 | |
| Age, Continuous | years | 22.0 (21.0 to 24.0) | 24.8 (22.0 to 26.0) | 26.8 (24.0 to 34.0) | 21.6 (19.0 to 25.0) | 22.2 (19.0 to 25.0) | 23.5 (19.0 to 34.0) |
| Sex: Female, Male: Female | Participants | 3 | 3 | 2 | 4 | 1 | 13 |
| Sex: Female, Male: Male | Participants | 2 | 2 | 3 | 1 | 4 | 12 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 1 | 0 | 0 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 4 | 4 | 4 | 5 | 5 | 22 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Weight | kilograms | 73.6 (60.4 to 84.8) | 75.5 (68.8 to 91.2) | 72.0 (53.0 to 86.0) | 71.5 (63.2 to 91.8) | 78.4 (63.0 to 93.0) | 74.2 (53.0 to 93.0) |
| Body Mass Index | kg/m^2 | 24.3 (19.5 to 29.5) | 25.0 (22.0 to 27.8) | 23.4 (21.6 to 26.4) | 23.9 (21.7 to 29.0) | 23.9 (21.7 to 25.0) | 24.1 (19.5 to 29.5) |
6. Primary Endpoint
The registry lists the primary outcome as Number and Severity of Adverse Events After TB31F Administration, measured over Throughout study: solicited local adverse events (day 0 - day 7); solicited general adverse events and clinically significant laboratory abnormalities (day 0 - day 28); unsolicited adverse events (day 0 - day 84), serious adverse events (day 0 - day 84).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint records the number and severity of adverse events after TB31F administration. The registry’s population description specifies participants who experienced a grade 1, 2, or 3 local solicited event, general solicited event, unsolicited event, or laboratory adverse event, reported by group. The outcome description separately includes the occurrence of serious adverse events.
The endpoint brings together several safety-related categories, but their observation periods differ. Solicited local events are assessed through day 7. Solicited general events and clinically significant hematological and biochemical laboratory abnormalities are assessed through day 28. Unsolicited events and serious adverse events are assessed through day 84 or the end of study, as described in the registry. These windows matter: a count for one category does not necessarily cover the same follow-up period as a count for another.
Counting participants who experienced an event is useful for describing how many people in each group had recorded events. It is not the same as counting every event episode, measuring event duration, or estimating a comparative treatment effect. The registry does not report a more detailed breakdown of event severity beyond the stated grades, nor does it report a formal analysis linking individual events to TB31F.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted adverse-event results list no serious adverse events in any of the five groups. The registry also lists no deaths in any group. These are counts within this small, sequential phase 1 study, not evidence that serious events cannot occur. The number of participants at risk in each group is five, so the findings have limited ability to characterize uncommon outcomes.
For other adverse events, the registry lists 5 participants in Group 1, 4 in Group 2, 2 in Group 3, 5 in Group 4, and 4 in Group 5 as affected. Those counts are descriptive. They do not establish that one dose or route has a higher or lower risk than another. Allocation was non-randomized, and the groups differ by dose or route; the registry also describes sequential administration. Participant characteristics, timing, and observation opportunities therefore cannot be assumed equivalent across groups.
The registry’s primary outcome is broader than a single event type. It includes solicited local and general adverse events, laboratory abnormalities, unsolicited events, and serious adverse events, with different follow-up windows. The posted aggregate counts do not show which event categories account for the participants recorded as affected, the individual severity distribution, or whether a participant experienced more than one category. Those details are not reported in the registry record.
No numerical results for the listed serum concentration or functional transmission-reducing activity outcomes appear in the record; such results are not reported in the registry record. The record also lists no statistical analyses. Consequently, there are no reported confidence intervals, hypothesis tests, adjusted estimates, or formal comparisons to interpret. The observed counts should not be treated as evidence of a statistically established difference between doses.
In general, small groups produce imprecise estimates: a single participant’s outcome can make a substantial difference to the description of a group. A confidence interval would communicate uncertainty around an estimate, but the registry record does not report intervals for these adverse-event counts. The posted findings are best read as an account of observed events in this study rather than as a precise estimate of risk for a broader population.
9. Statistical Methods Explained
The registry describes a non-randomized, unmasked, sequential phase 1 study. These design features shape what can be learned from the results. The primary outcome is a count of participants with specified adverse events, and the posted results are reported by group. No statistical analyses are listed in the registry record.
What does a participant count represent?
A participant count indicates how many people in a group experienced an event under the registry’s outcome definition. It does not necessarily represent the total number of event episodes. If a participant experienced more than one type of event, a count across categories could overlap; the registry record does not report whether the displayed adverse-event counts overlap or how repeated events were handled. The event totals therefore should not be interpreted as unique event episodes or used to infer an unreported number of affected participants across the study.
The registry identifies the primary outcome as number and severity of adverse events, while the population description specifies participants experiencing grade 1, 2, or 3 events. The posted group results provide affected-participant counts, but the record does not provide a separate severity distribution for each group. It is therefore possible to describe the counts as posted, but not to reconstruct the severity profile or a participant-level analysis from these data.
Why does the design limit comparisons?
Random allocation is a general method for balancing measured and unmeasured participant characteristics across treatment groups. This study is explicitly non-randomized. It uses sequential dose groups, and the groups differ in dose or route. Thus, group differences in the posted counts cannot be attributed solely to dose or route. They may also reflect group composition, order of enrollment, or other factors; the registry does not report enough information to assess those possibilities.
In general, an unmasked design means participants and study personnel are not described as blinded to assignment. That can affect the reporting or assessment of subjective outcomes. The registry identifies masking as none, but does not report procedures used to minimize assessment bias. Solicited events and laboratory abnormalities have different measurement characteristics, and the registry’s aggregate result does not permit separate evaluation of how ascertainment may have influenced each category.
How should uncertainty be understood?
In general, a confidence interval describes the range of values compatible with an estimate under a statistical model. It conveys uncertainty beyond the point estimate alone. No confidence intervals or other uncertainty estimates for adverse events are reported in the registry record. With five participants per group, the counts are particularly limited as estimates of event frequency outside the study. A count of zero serious adverse events in a group is an observation in that group, not proof that the underlying risk is zero.
In general, over-dispersion matters when count data vary more than a chosen statistical model expects. A model that ignores excess variability can understate uncertainty. However, this endpoint is described as participants with an event, not as an event rate or recurrent-event count, and the registry record gives no model, dispersion estimate, or analysis plan. It is therefore not possible to say that an over-dispersion adjustment was needed or used.
What can the planning illustration establish?
The registry’s planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power. The record does not report the resulting planning values in the trial details, and the non-randomized groups are not a like-for-like control comparison. No inference about the trial’s original sample-size justification can be made: that justification is not reported in the registry record.
More generally, a planning calculation depends on the effect and assumptions chosen for it. It does not establish that an effect is real, nor does it substitute for a statistical analysis of trial data. Because the registry reports no formal analysis results, no inferential conclusion should be drawn from a planning illustration.
What is unavailable for reanalysis?
The registry record does not report participant-level data, event-level details, analysis populations, missing-data handling, or inferential results. It also does not report a statistical model for the primary endpoint. Without those details, it is not possible to reproduce an adjusted analysis, assess the effect of missing observations, or estimate comparative uncertainty from the posted counts alone. The appropriate statistical reading is descriptive: report the registered group counts and retain the design limitations when considering them.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary adverse-event outcome and secondary outcomes for serum concentration of TB31F and functional transmission-reducing activity. It also describes several adverse-event categories and follow-up windows within the primary outcome. The registry record does not report a multiplicity strategy, such as how several outcomes or comparisons would be handled when drawing inferential conclusions. It does not report formal hypothesis tests or analysis results, so there is no stated adjustment to evaluate.
Missing-data methods are not reported in the registry record. The record does not specify whether missing observations were expected, how incomplete follow-up would be handled, or whether participants with missing measurements would be included in particular analyses. The posted adverse-event counts do not explain whether every participant completed follow-up for every event window. These details should not be inferred from the fact that the trial is marked completed.
Analysis populations are also not reported in the registry record. There is no stated definition of which participants would be included in safety, pharmacokinetic, or pharmacodynamic analyses, nor a description of exclusions from those analyses. No participant-level dataset or analysis plan is listed in the registry record for this record.
These omissions matter because multiple outcomes, differing follow-up windows, and incomplete observations can affect how results are summarized and compared. In general, multiplicity procedures are used to control the chance of misleading positive findings when several statistical tests are conducted, while missing-data procedures make explicit how unavailable measurements are treated. Here, the record does not describe such procedures. The posted counts can still be read descriptively, but no inferential claim about multiple outcomes or missing observations is supported by the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Group 1 - 0,1mg/kg TB31F | 0 | 5 | 0.0% |
| Group 2 - 1mg/kg TB31F | 0 | 5 | 0.0% |
| Group 3 - 3mg/kg TB31F | 0 | 5 | 0.0% |
| Group 4 - 10mg/kg TB31F | 0 | 5 | 0.0% |
| Group 5 - 100mg TB31F | 0 | 5 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1 - 0,1mg/kg TB31F | 0 of 5 |
| Group 2 - 1mg/kg TB31F | 0 of 5 |
| Group 3 - 3mg/kg TB31F | 0 of 5 |
| Group 4 - 10mg/kg TB31F | 0 of 5 |
| Group 5 - 100mg TB31F | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group 1 - 0,1mg/kg TB31F | 5 of 5 |
| Group 2 - 1mg/kg TB31F | 4 of 5 |
| Group 3 - 3mg/kg TB31F | 2 of 5 |
| Group 4 - 10mg/kg TB31F | 5 of 5 |
| Group 5 - 100mg TB31F | 4 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1 - 0,1mg/kg TB31F | Group 2 - 1mg/kg TB31F | Group 3 - 3mg/kg TB31F | Group 4 - 10mg/kg TB31F | Group 5 - 100mg TB31F |
|---|---|---|---|---|---|---|
| Fatigue (R53) | General disorders | 5 of 5 | 2 of 5 | 1 of 5 | 3 of 5 | 2 of 5 |
| Headache (R51) | General disorders | 1 of 5 | 2 of 5 | 0 of 5 | 3 of 5 | 0 of 5 |
| Pain at site of injection (M79.68) | Skin and subcutaneous tissue disorders | 0 of 5 | 0 of 5 | 1 of 5 | 0 of 5 | 4 of 5 |
| Redness at site of injection (L53.8) | Skin and subcutaneous tissue disorders | 0 of 5 | 1 of 5 | 0 of 5 | 0 of 5 | 0 of 5 |
| Fever (R50.9) | General disorders | 0 of 5 | 0 of 5 | 0 of 5 | 1 of 5 | 0 of 5 |
| Myalgia (M79.17) | Musculoskeletal and connective tissue disorders | 1 of 5 | 0 of 5 | 0 of 5 | 0 of 5 | 0 of 5 |
| Depressed feeling (F38) | Psychiatric disorders | 1 of 5 | 0 of 5 | 0 of 5 | 0 of 5 | 0 of 5 |
| Diahrrea (R19.4) | Gastrointestinal disorders | 1 of 5 | 0 of 5 | 0 of 5 | 0 of 5 | 0 of 5 |
| Sore Throat (J02.3) | Infections and infestations | 1 of 5 | 0 of 5 | 0 of 5 | 0 of 5 | 0 of 5 |
| Stomach Ache (R10.4) | Gastrointestinal disorders | 0 of 5 | 0 of 5 | 0 of 5 | 1 of 5 | 0 of 5 |
The serious adverse-event results list zero affected participants in each group, and the death count is zero in each group. Each group has five participants at risk according to the registry. Read these as observed counts during the study’s recorded follow-up, not as proof that serious adverse events or deaths are impossible with TB31F.
The primary outcome specifies serious adverse events from day 0 through day 84 or the end of study. Other categories have shorter or different windows: solicited local events through day 7, and solicited general events and clinically significant laboratory abnormalities through day 28. Consequently, the absence of recorded serious adverse events should not be confused with an absence of all adverse events. The registry lists other adverse-event counts of 5, 4, 2, 5, and 4 for Groups 1 through 5, respectively.
A zero count in a small group provides limited information about the frequency of uncommon events. It also does not establish equal safety across doses or routes. The study was non-randomized and sequential, and the groups do not form a like-for-like control comparison. The registry does not report a statistical comparison or uncertainty interval for the serious-event findings, nor detailed event narratives or a separate breakdown by severity.
12. What the Result Does, and Does Not, Mean
The registry describes a phase 1 study designed to assess safety and tolerability while also evaluating TB31F serum concentration and functional transmission-reducing activity. The posted safety results record no serious adverse events and no deaths in the five groups. They also record other adverse-event counts of 5, 4, 2, 5, and 4 for Groups 1 through 5. These are descriptive observations from the study, not estimates that establish how the groups differ.
The findings do not establish a causal dose-response relationship. Participants were not randomized, the groups received different doses or routes, and administration was sequential. There is no randomized control group against which to separate treatment effects from other differences. The registry reports no formal statistical analyses, uncertainty intervals, or comparative estimates. It also does not give enough detail to assess the severity and category composition of the other adverse events.
The results do not answer every question raised by the trial’s aims. Serum concentration and functional transmission-reducing activity are listed as secondary outcomes, but numerical results for them are not reported in the registry record. Nor do the posted safety counts establish longer-term safety beyond the registry’s stated observation windows or describe outcomes in populations other than healthy malaria-naïve adults.
In general, a small early-phase study can provide descriptive information about observations made during a controlled study process and can inform further investigation. Its counts alone cannot establish the frequency of rare events or support a broad safety conclusion. The appropriate interpretation is limited to the outcomes and follow-up recorded for these groups. The registry record supports reporting what was observed; it does not support claims that TB31F works, does not work, or has a particular comparative effect.
13. Why This Trial Matters Statistically
This study is statistically instructive because the design and the outcome format place clear limits on interpretation. A reader may see different adverse-event counts across groups and be tempted to treat them as a dose comparison. But the groups were not randomized, were enrolled sequentially, and received different doses or routes. Descriptive differences are not, by themselves, evidence of a dose effect.
The endpoint also illustrates why outcome definitions matter. Solicited local events, solicited general events, laboratory abnormalities, unsolicited events, and serious adverse events are not interchangeable. Their follow-up periods differ, and the record’s primary outcome includes both counts and severity. Yet the posted results do not give a detailed breakdown by event category and severity. The headline group counts therefore provide only part of the information needed to characterize the safety observations.
Small group sizes make uncertainty especially important. In general, a count from a small group is sensitive to individual observations and does not precisely characterize uncommon outcomes. A zero count is not evidence that the underlying event risk is zero. The lack of reported uncertainty intervals and formal analyses further emphasizes that the posted results are descriptive rather than comparative estimates.
The record’s secondary outcomes raise another useful distinction: listing an outcome is not the same as reporting its results. TB31F serum concentration and functional transmission-reducing activity are named, but their numerical findings are not reported in the registry record. Keeping registered aims separate from posted results helps prevent conclusions from being drawn from outcomes without available data. Together, these features make this trial a useful example of reading early-phase findings in light of design, outcome definition, and reporting completeness.
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 principal limitation for interpreting the results is the non-randomized, sequential design. There is no randomized control group, and dose groups also differ by route for the subcutaneous group. Group counts therefore cannot establish comparative safety effects or isolate the influence of dose or route. The registry record does not report a statistical analysis addressing these design constraints.
Each group is described as having five participants. This limits the precision of descriptive safety findings, particularly for uncommon events. The zero serious adverse-event and death counts should be read within that context, not as evidence that such outcomes cannot occur. The record reports affected-participant counts for other adverse events, but does not provide detailed event-level descriptions, a severity distribution by group, or a breakdown by event category.
Follow-up periods vary by adverse-event category, and the registry record does not explain whether all participants completed every observation window or how missing observations were handled. It does not report analysis populations, confidence intervals, hypothesis tests, or the statistical plan. The full administration descriptions for some groups are truncated in the registry record, limiting assessment of those details.
The secondary outcomes are listed without numerical results in the registry record. As a result, the posted information cannot characterize the pharmacokinetic or pharmacodynamic findings. The record also does not report enough information to assess how outcome ascertainment was conducted beyond the stated unmasked design and outcome definitions. These limitations restrict interpretation to the posted descriptive counts and the registered design details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of TB31F — NCT04238689.
- Registry record last updated 2023-03-27; status last verified 2021-01.
- Results first posted 2023-03-27.
- 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.
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18. Record Summary
NCT04238689 is a completed phase 1, non-randomized, unmasked, sequential study of monoclonal antibody TB31F in healthy malaria-naïve adults in the Netherlands. The registry lists Radboud University Medical Center as sponsor and an enrollment of 25. Five groups are described: intravenous TB31F at 0.1 mg/kg, 1 mg/kg, 3 mg/kg, or 10 mg/kg, and subcutaneous TB31F at 100mg; each group description specifies five participants.
The primary outcome concerns adverse-event numbers and severity across several categories and follow-up periods. The registry lists no serious adverse events or deaths in any group, and other adverse-event counts of 5, 4, 2, 5, and 4 across Groups 1 through 5. Serum concentration and functional transmission-reducing activity are listed as secondary outcomes, but numerical results for them are not reported in the registry record. The record lists no statistical analyses. The findings are descriptive and do not constitute a randomized comparison of dose or route.