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 Study of VMP001 and AS01B (Adjuvant Formulation) in Healthy Malaria-Naïve Adults (NCT01157897), a non-randomized phase 1, phase 2 study. The primary outcome is Occurrence of Solicited Adverse Events Over a 7 Day Follow-up Period After Each Immunization (the Day of the Immunization and 6 Subsequent Days) During the Vaccination Phase.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01157897 |
| Phase | Phase 1, Phase 2 |
| Condition | Malaria, Plasmodium Vivax |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 41 |
| Arms in the primary outcome | n/a |
| Lead sponsor | U.S. Army Medical Research and Development Command |
| Results posted | Yes |
2. Clinical Question
Population
Healthy, malaria-naïve adults in the United States were enrolled. The study is described as first-in-humans and focused on a candidate vaccine for Plasmodium vivax malaria.
Intervention
Participants in three cohorts received intramuscular VMP001 formulated with AS01B, at 15 μg, 30 μg, or 60 μg per vaccination. Each cohort was scheduled for three vaccinations, with timing differing by cohort, followed by P. vivax sporozoite challenge on day 98.
Comparator
A control group received no vaccinations and underwent P. vivax sporozoite challenge on day 98. Allocation was non-randomized, so the groups should not be treated as interchangeable or as a like-for-like causal comparison.
Primary question
The primary endpoint concerns the number of participants with solicited adverse events during the 7 days after each immunization, including the immunization day and 6 subsequent days. The control group was not included in this endpoint evaluation. The study also describes immunogenicity and efficacy goals, including time to parasitemia after challenge, but outcome analyses are not posted in the registry record.
3. Trial Design
This was a phase 1/2, open-label, non-randomized, parallel-group study of VMP001 with AS01B in healthy malaria-naïve adults. The registry record reports enrollment of 41 and identifies the U.S. Army Medical Research and Development Command as the sponsor. The study is marked completed; the recorded start was 2010-07 and primary completion was 2012-01.
Three vaccination cohorts received different VMP001 doses and schedules. The 15 μg cohort was scheduled to receive vaccinations on days -1 or 0, 28, and 84. The 30 μg cohort was scheduled for days 14, 42, and 84, and the 60 μg cohort for days 28, 56, and 84. All three cohorts were scheduled for P. vivax sporozoite challenge on day 98. The control group received no vaccinations and was challenged on day 98.
There was no masking, and allocation was non-randomized. The groups therefore differ by design and cannot be assumed to be balanced on measured or unmeasured characteristics. Any contrast between a vaccination cohort and control is descriptive rather than a randomized treatment comparison. Reasons for cohort allocation, details of sequence or timing decisions beyond the schedules, and a protocol-level explanation of the design are not reported in the registry record.
The listed safety denominators are 9, 8, and 10 for the three vaccination cohorts and 6 for control. These are the denominators shown in the adverse-event record; how they relate to the overall enrollment of 41 is not reported. The registry lists secondary outcomes of time to parasitemia and geometric mean anti-VMP001 antibody titers in serum for immunogenicity and efficacy populations. Results and analyses for those outcomes are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Cohort 1: 15 μg VMP001 | Cohort 2: 30 μg VMP001 | Cohort 3: 60 μg VMP001 | Control |
|---|---|---|---|---|
| STARTED | 10 | 10 | 10 | 6 |
| COMPLETED | 8 | 8 | 10 | 5 |
| NOT COMPLETED | 2 | 2 | 0 | 1 |
Reasons for not completing this period:
| Reason | Cohort 1: 15 μg VMP001 | Cohort 2: 30 μg VMP001 | Cohort 3: 60 μg VMP001 | Control |
|---|---|---|---|---|
| Lost to Follow-up | 2 | 0 | 0 | 1 |
| Relocated | 0 | 2 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Control group was not included in the evaluation.
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 | Cohort 1: 15 μg VMP001 | Cohort 2: 30 μg VMP001 | Cohort 3: 60 μg VMP001 | Control | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 10 | 10 | 10 | 6 | 36 | |
| Age, Continuous | years | 32.1 (SD 8.3) | 29.4 (SD 8.2) | 28.7 (SD 8.0) | 25.0 (SD 7.2) | 30.1 (SD 8.0) |
| Sex: Female, Male: Female | Participants | 4 | 2 | 4 | 3 | 13 |
| Sex: Female, Male: Male | Participants | 6 | 8 | 6 | 3 | 23 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 10 | 10 | 10 | 6 | 36 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 0 | 1 | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 | 0 | 4 |
| Race (NIH/OMB): White | Participants | 7 | 9 | 8 | 4 | 28 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 1 | 1 |
| Region of Enrollment: United States | participants | 10 | 10 | 10 | 6 | 36 |
6. Primary Endpoint
The registry lists the primary outcome as Occurrence of Solicited Adverse Events Over a 7 Day Follow-up Period After Each Immunization (the Day of the Immunization and 6 Subsequent Days) During the Vaccination Phase, measured over 7 days after immunization.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants with AEs |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with solicited adverse events during the 7-day follow-up period after each immunization. The period comprises the day of immunization and 6 subsequent days. It applies during the vaccination phase, and the registry specifies that the control group was not included in this evaluation.
Counting participants with an event is a binary-outcome approach: each participant is classified according to whether an event occurred within the specified observation period. This can make the result straightforward to interpret as a count of affected participants, but it does not by itself describe how many events each participant experienced, how severe they were, or how long they lasted. The registry’s endpoint description does not state how repeated events were handled in the participant count, or provide event-level results for this endpoint.
Solicited events are useful in an early safety study because prespecified monitoring after vaccination can consistently capture particular symptoms or reactions. The short, stated follow-up window focuses the measure on events soon after immunization. That focus also limits what the endpoint can say: it does not represent all possible adverse events across the full study or establish a longer-term safety profile. The registry record describes the endpoint and follow-up but does not report a primary endpoint analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies an early-stage study intended to assess safety, reactogenicity, immunogenicity, and efficacy of VMP001 with AS01B. It reports a primary safety endpoint but lists 0 analyses. As a result, the registry information does not give an analyzed primary endpoint estimate, uncertainty interval, or statistical test. The number of participants with solicited adverse events for the specified 7-day periods is not reported in the registry record.
Separate adverse-event fields list serious adverse-event counts by group. The record lists 1 participant affected among 9 at risk in the 15 μg cohort, 0 among 8 in the 30 μg cohort, 0 among 10 in the 60 μg cohort, and 1 among 6 in control. These are descriptive counts. The registry does not report a comparative analysis or uncertainty measures for them, and the non-randomized allocation means the groups should not be read as a balanced causal comparison. The record’s serious-event term list includes “Breast cancer in situ” at 16.7%; it does not identify a causal relationship in that listing.
The record also lists other adverse-event counts: 9 participants affected among 9 at risk in the 15 μg cohort, 8 among 8 in the 30 μg cohort, 10 among 10 in the 60 μg cohort, and 6 among 6 in control. These are not substitutes for the primary solicited-event endpoint. Their definitions and observation periods are not specified in the registry record here, so they should not be interpreted as the endpoint’s 7-day post-immunization results.
The study description includes a P. vivax challenge and secondary outcomes involving time to parasitemia and antibody titers. However, no outcome analyses are posted in the registry record. Consequently, the stated aims do not establish what the study found about immunogenicity or efficacy. The available registry information supports a description of the study design and posted event counts, not a conclusion about comparative effects or the precision of an efficacy estimate.
The sample-size figures associated with the posted results are planning illustrations based on an observed effect, with stated assumptions for a hypothetical comparison. They are not observed power and do not replace an analysis of the trial data. Because the registry record does not contain the outcome analyses needed to establish an observed effect, those planning figures should not be interpreted as evidence of a trial result.
9. Statistical Methods Explained
For this study, the primary outcome is a count of participants with an event, rather than a continuous measurement such as an antibody concentration. In general, a binary outcome records whether each participant meets a defined event criterion during a specified period. Reporting the number affected alongside the number at risk helps readers understand the scale of the count. It does not, by itself, capture event frequency per person, duration, severity, or the timing of events within that period.
What does the endpoint’s time window mean?
The primary endpoint covers the day of immunization and 6 subsequent days after each immunization. Restricting observation to a defined window makes the endpoint more specific: it addresses solicited events during that interval, rather than all events across all follow-up. Because participants were scheduled for multiple immunizations, the endpoint description refers to follow-up after each immunization. The registry record does not explain whether a participant with an event after more than one vaccination is counted once or in more than one assessment, nor does it provide event-level results that would clarify the handling.
Repeated measurements within the same participant are generally related rather than statistically independent. In general, an analysis of repeated event observations may need to account for that within-person dependence. The registry record does not report an analysis method for the repeated post-immunization periods, so it is not possible to say whether or how such dependence was handled.
How should group comparisons be read?
Allocation was non-randomized and the study was open-label. In general, randomization helps balance participant characteristics across groups, while masking can reduce the influence of expectations on some assessments. Neither feature is present. Differences between groups could therefore reflect differences in who entered each group, the dose and schedule, or other factors, as well as any intervention-related effect. A direct numerical contrast would not establish a causal effect. The registry record does not report an adjusted analysis or the factors that might have been considered for adjustment.
The control group received no vaccinations, and the primary solicited-event endpoint explicitly excluded control. Consequently, that primary endpoint is not a direct vaccinated-versus-control comparison. The separate adverse-event counts include a control group, but the registry record does not report a statistical comparison of those counts.
What do uncertainty measures add?
In general, a confidence interval describes the range of values compatible with an estimate under the analysis assumptions, and its width indicates precision. Small group counts can leave substantial uncertainty even when the observed count is clear. The registry record does not post confidence intervals or other uncertainty measures for the adverse-event counts. No p-values or analyzed primary endpoint estimate are reported, so statistical significance cannot be assessed from the posted registry information.
The sample-size material uses a planning illustration based on an observed effect and states assumptions of two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. For time-to-event calculations, the stated output is a total event count; for other outcomes, it is participants per arm. Such calculations are general planning tools under their assumptions. They are not observed trial results, do not establish that the study had adequate power, and should not be read as a retrospective measure of power. The study’s own sample-size justification is not reported in the registry record.
What is not available for evaluating analysis choices?
The registry record lists 6 outcome measures and 0 analyses. It names time to parasitemia and geometric mean antibody titers as secondary outcomes, but does not report their analysis results. The statistical analysis plan, any interim analyses, the handling of missing observations, and any multiplicity strategy are not reported in the registry record. Without those details and the outcome analyses, the listed design aims cannot be translated into estimates of effect or precision.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 6 outcome measures but 0 analyses. It names several secondary outcomes, including time to parasitemia for the immunogenicity population and geometric mean anti-VMP001 antibody titers in serum for immunogenicity and efficacy populations. Results for these outcomes, including estimates and uncertainty measures, are not reported in the registry record.
When a study evaluates multiple outcomes or makes multiple comparisons, the chance of at least one apparently unusual result can increase. In general, a prespecified multiplicity strategy can clarify how multiple statistical tests are interpreted. The registry record does not report a multiplicity plan, whether outcomes were hierarchically tested, or whether any adjustment was used. It also does not report interim analyses or a statistical analysis plan. These details should not be inferred from the number of listed outcomes.
Missing-data methods and the number of participants with missing outcome information are not reported in the registry record. The overall enrollment is 41, while the adverse-event fields list denominators of 9, 8, 10, and 6 across the four groups. The reason those listed denominators differ from total enrollment is not reported; the counts alone do not establish whether the difference reflects eligibility, follow-up, analysis populations, or missing data.
The record names immunogenicity and efficacy populations for secondary outcomes, but the population definitions and analysis membership are not reported in the registry record. Without the population rules and missing-data approach, readers cannot determine how participants were included in each outcome analysis. No assumption should be made that all enrolled participants contributed to every endpoint.
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 |
|---|---|---|---|
| Cohort 1: 15 μg VMP001 | 1 | 9 | 11.1% |
| Cohort 2: 30 μg VMP001 | 0 | 8 | 0.0% |
| Cohort 3: 60 μg VMP001 | 0 | 10 | 0.0% |
| Cohort 4: Control | 1 | 6 | 16.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1: 15 μg VMP001 | 0 of 9 |
| Cohort 2: 30 μg VMP001 | 0 of 8 |
| Cohort 3: 60 μg VMP001 | 0 of 10 |
| Cohort 4: Control | 0 of 6 |
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 |
|---|---|
| Cohort 1: 15 μg VMP001 | 9 of 9 |
| Cohort 2: 30 μg VMP001 | 8 of 8 |
| Cohort 3: 60 μg VMP001 | 10 of 10 |
| Cohort 4: Control | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1: 15 μg VMP001 | Cohort 2: 30 μg VMP001 | Cohort 3: 60 μg VMP001 | Cohort 4: Control |
|---|---|---|---|---|---|
| Breast cancer in situ | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 9 | 0 of 8 | 0 of 10 | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1: 15 μg VMP001 | Cohort 2: 30 μg VMP001 | Cohort 3: 60 μg VMP001 | Cohort 4: Control |
|---|---|---|---|---|---|
| Fatigue | General disorders | 5 of 9 | 6 of 8 | 10 of 10 | 5 of 6 |
| Nausea | Gastrointestinal disorders | 5 of 9 | 6 of 8 | 9 of 10 | 1 of 6 |
| Myalgia | Musculoskeletal and connective tissue disorders | 5 of 9 | 5 of 8 | 8 of 10 | 0 of 6 |
| Chills | General disorders | 4 of 9 | 6 of 8 | 7 of 10 | 0 of 6 |
| Pyrexia | General disorders | 5 of 9 | 6 of 8 | 5 of 10 | 1 of 6 |
| Back pain | Musculoskeletal and connective tissue disorders | 4 of 9 | 4 of 8 | 9 of 10 | 0 of 6 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 4 of 9 | 5 of 8 | 5 of 10 | 1 of 6 |
| Abdominal pain | Gastrointestinal disorders | 3 of 9 | 1 of 8 | 7 of 10 | 1 of 6 |
| Upper respiratory tract infection | Infections and infestations | 2 of 9 | 3 of 8 | 3 of 10 | 2 of 6 |
| Cold sweat | Skin and subcutaneous tissue disorders | 2 of 9 | 3 of 8 | 4 of 10 | 1 of 6 |
Serious events with the highest arm-level rate: breast cancer in situ (16.7%).
The serious adverse-event fields list 1 participant affected among 9 at risk in the 15 μg cohort, 0 among 8 in the 30 μg cohort, 0 among 10 in the 60 μg cohort, and 1 among 6 in control. The registry also reports 0 deaths in each group. These figures are participant counts, not a comparative analysis, and the record does not provide uncertainty intervals or an assessment of whether events were related to vaccination or challenge.
The serious-event term list includes “Breast cancer in situ” at 16.7%. The registry record does not state in that listing which group the term belongs to, its timing, or whether investigators considered it related to an intervention. The percentage should therefore be read as a posted term-level value, not as evidence of causation or as a group-specific risk estimate.
Serious adverse events are distinct from the primary solicited adverse-event endpoint, which covers a defined 7-day period after each immunization and excludes control. The serious-event fields should not be used as a proxy for that primary endpoint. The non-randomized design also limits direct comparisons across groups. Counts describe what the record lists; they do not establish that a treatment caused or prevented an event.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this was a first-in-humans phase 1/2 study with three VMP001 dose cohorts, a no-vaccination control group, and P. vivax sporozoite challenge. It describes a primary safety endpoint focused on solicited events during a 7-day period after each immunization. It also lists group-level serious and other adverse-event counts.
Those details do not amount to a complete analysis of the trial outcomes. No analyses are posted in the registry record, and the primary endpoint results are not reported. The record therefore does not provide a statistical estimate of the primary safety outcome or its precision. It also does not report results for the listed time-to-parasitemia or antibody-titer outcomes. The study aims alone cannot show whether a difference in those outcomes occurred.
The serious adverse-event counts are descriptive and arise from a non-randomized, open-label design. They do not support a like-for-like causal comparison between vaccination cohorts and control. The listed serious-event term should not be treated as evidence that an intervention caused the event. The registry does not report attribution or a comparative safety analysis.
General sample-size planning calculations do not fill these gaps. They illustrate assumptions for hypothetical designs and are not a measure of the study’s observed power or a substitute for outcome estimates. Likewise, the difference between overall enrollment and the event denominators cannot be explained from the registry record alone.
In short, the posted information is useful for understanding the study’s structure and the event counts recorded by group. It does not establish the magnitude, precision, or causal interpretation of safety, immunogenicity, or efficacy outcomes. Conclusions beyond those descriptive details would require outcome analyses and methodological details that are not reported in the registry record.
13. Why This Trial Matters Statistically
Early-phase vaccine studies bring together several statistical issues that matter for interpreting later evidence. This study combined three dose cohorts, differing vaccination schedules, a no-vaccination control, and a challenge procedure. Its open-label, non-randomized structure makes it particularly important to distinguish descriptive group counts from causal comparisons.
The primary endpoint is narrowly defined by event type and follow-up period: solicited adverse events after each immunization over 7 days. A clearly delimited endpoint can make safety monitoring interpretable, but the absence of posted endpoint results means readers cannot assess the corresponding observed counts or their precision. The separate serious adverse-event counts answer a different descriptive question and should not be substituted for the primary endpoint.
The study also illustrates why analysis populations and denominators matter. Overall enrollment is 41, while the adverse-event record lists group denominators of 9, 8, 10, and 6. Without an explanation of how those sets relate, readers should not assume that every enrolled participant contributed to every outcome or infer a reason for the difference.
Finally, the registry lists immunogenicity and challenge-related outcomes but no analyses. This distinction between planned measurement and reported result is central to evidence interpretation: a stated objective does not tell readers what the analysis found. In general, a transparent analysis plan, clear population definitions, missing-data handling, and uncertainty measures help readers evaluate the strength and limits of trial evidence. Those details are not reported in the registry record, making careful descriptive interpretation especially important.
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 of the posted information is the lack of outcome analyses. The registry record lists 0 analyses, so it does not report results for the primary solicited adverse-event endpoint or the named secondary outcomes. Estimates, uncertainty intervals, and statistical tests are not reported. This prevents assessment of the magnitude and precision of those outcomes.
The design was non-randomized and open-label. Cohort assignment and the different vaccination schedules limit the comparability of groups, while the control group was excluded from the primary solicited-event evaluation. Descriptive counts cannot resolve these design limitations or establish causal effects. The record does not report adjusted comparisons.
There is also an unresolved denominator issue: the registry reports enrollment of 41, whereas the adverse-event fields list group denominators of 9, 8, 10, and 6. Reasons for the difference are not reported in the registry record. It also does not give definitions for the analysis populations, missing-data handling, or details that reconcile enrollment with outcome-specific denominators.
The primary endpoint description identifies a 7-day window after each immunization but does not explain how repeated events or events across multiple vaccination periods were handled in participant-level counts. Serious adverse-event fields are reported separately, with no posted attribution analysis or uncertainty measures. The serious-event term listing does not identify group membership or causal relationship.
Finally, the statistical analysis plan, sample-size justification, interim analyses, and multiplicity approach are not reported in the registry record. These limitations concern what can be concluded from the posted record; they do not establish that the unreported analyses or procedures did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of VMP001 and AS01B (Adjuvant Formulation) in Healthy Malaria-Naïve Adults — NCT01157897.
- Registry record last updated 2019-05-29; status last verified 2019-05.
- Results first posted 2019-05-29.
- 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
NCT01157897 is a completed phase 1/2, open-label, non-randomized, parallel-group study sponsored by the U.S. Army Medical Research and Development Command. It enrolled 41 healthy malaria-naïve adults and examined VMP001 with AS01B across 15 μg, 30 μg, and 60 μg vaccination cohorts, alongside a no-vaccination control. Each group was scheduled for P. vivax sporozoite challenge on day 98.
The primary endpoint was the number of participants with solicited adverse events during the 7 days after each immunization; control was excluded from that endpoint. The registry lists serious and other adverse-event counts by group, but no outcome analyses. Time to parasitemia and anti-VMP001 antibody titers are listed as secondary outcomes without reported results. The record does not provide the statistical analysis plan, missing-data methods, or an explanation of how the adverse-event denominators relate to overall enrollment.