Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1 (NCT04201431), a non-randomized phase 1, phase 2 study. The primary outcome is Safety of the PvDBPII-Matrix M1 Vaccine Candidate, Assessed Through Collection of Data on the Frequency, Duration and Severity of Solicited and Unsolicited Adverse Events..

2. Clinical Question

The trial was designed as a first-in-human Phase I/IIa study to assess safety, immunogenicity and efficacy in healthy adults. Its registry description includes blood-stage controlled human malaria infection (CHMI) after vaccination, but the primary outcome recorded in the registry is a safety count, not a measure of vaccine efficacy. The registry record does not report a result for the primary endpoint in the information available for this analysis.

The secondary outcomes included humoral and cellular immunogenicity, immune measurements associated with a reduced parasite multiplication rate (PMR), and assessment of the durability of any PMR reduction among Group 3 volunteers undergoing a fourth vaccination and rechallenge. The registry record does not report the results of those outcomes. As a result, the clinical question that can be addressed from the posted counts is limited to the recorded safety summaries, not whether vaccination changed parasite outcomes or immune responses.

Because the trial was non-randomized and sequential, the groups do not supply a randomized comparison of vaccinated participants against an untreated control. Differences between groups could reflect how participants entered the study or which procedures they underwent, rather than a treatment effect. The posted group counts are best read as descriptive observations within the recorded groups.

3. Trial Design

This was a Phase I/IIa, first-in-human, open-label trial of PvDBPII/Matrix-M1. The registry lists the allocation as non-randomized, masking as none, and the model as sequential. The enrollment was 24. The status is completed; the recorded start date is 2020-01-24 and the primary completion date is 2022-07-14.

Group 1 was planned to include up to 12 volunteers. Its participants were to receive three doses of PvDBPII 50ug/Matrix M1 50ug at 1, 2 and 12-18 months, followed by blood-stage CHMI 2-4 weeks after the third vaccination. If fewer than 8 volunteers completed the study in Group 1, the description says new volunteers would be recruited into Group 2 to make up a total of 10 to 12 volunteers completing three vaccinations and CHMI across Groups 1 and 2. The Group 2 description is incomplete in the registry record, so additional schedule details are not reported in the registry record.

Up to 6 volunteers from Group 1 were to receive a fourth dose in Group 3, 5 months after the third dose, before a second CHMI 2-4 weeks later. This arrangement means Group 3 was not an independent randomized arm: it consisted of volunteers from Group 1 selected for an additional vaccination and rechallenge.

The adverse-event summaries list 12 participants at risk in Group 1, 4 in Group 2, and 5 in Group 3. These are group-specific safety denominators, and the registry record does not establish that the groups are mutually exclusive; Group 3 is described as drawn from Group 1. They should therefore not be combined or interpreted as the allocation of all enrolled participants without further information.

The registry record does not report a randomized comparator, a masking procedure, or a formal statistical analysis plan. The trial's sequential structure is relevant to interpretation: groups may differ in timing, eligibility or procedures, and their event counts are descriptive rather than a direct comparative estimate of treatment 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.

Vaccinations and Primary CHMI

Reasons for not completing this period:

4th Vaccination and Secondary CHMI

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: Group 3 participants are a subset 5 participants from Group 1 who completed 3 vaccinations and primary CHMI and subsequently received a 4th vaccination and secondary CHMI. Group 3 participants are therefore not separately shown here.

6. Primary Endpoint

The registry lists the primary outcome as Safety of the PvDBPII-Matrix M1 Vaccine Candidate, Assessed Through Collection of Data on the Frequency, Duration and Severity of Solicited and Unsolicited Adverse Events., measured over 12 months.

The primary endpoint is a count of volunteers with a specified safety event. It includes a grade 3 solicited or unsolicited adverse event within 28 days after vaccination, or a serious adverse event at any time during the study period. The endpoint title describes safety assessment through the frequency, duration and severity of solicited and unsolicited adverse events, while the endpoint description defines the reported participant count using the severe-event criteria and time windows.

Counting participants with an event is useful in early clinical research because it records how many people experienced an event meeting the endpoint definition. The count is distinct from the total number of events: one participant may experience more than one event, but a participant count records whether that person met the definition. The registry record specifies participants as the unit.

Safety outcomes are important in a first-in-human study because the intervention is being assessed in people and adverse events are a central part of its evaluation. General statistical interpretation: a count alone does not describe event timing, duration, recurrence or severity beyond the definition used. Those details require their own reported summaries. The registry record does not report the primary endpoint result as a single count in the information available for this analysis, so the serious-event counts should not be assumed to represent the full primary endpoint.

The primary timeframe is recorded as 12 months, while the endpoint definition also specifies a 28-day window for grade 3 solicited or unsolicited events and the full study period for serious events. These distinct windows matter when interpreting which events are included. The registry record does not report further details of endpoint adjudication or event ascertainment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Outcome data in this record are expressed as counts of participants with an event. For a binary outcome, each participant is classified according to whether the event definition was met. The registry also lists the number at risk, which supplies the denominator for each group-specific count. A count without its denominator is difficult to interpret; together, the count and denominator describe how many of the listed participants experienced the recorded event. No new event rates are calculated.

General statistical explanation: binary event data can be summarized descriptively before any comparison is considered. A descriptive count answers how many participants had an event in the recorded group. It does not by itself show that one intervention caused more or fewer events than another. A comparative analysis requires a clearly defined contrast and an appropriate design or method. In this trial, allocation was non-randomized and there was no masking, so unadjusted differences between groups would not have the protection against selection differences that random assignment is intended to provide.

What does the denominator mean?

The adverse-event summary gives separate at-risk counts for Groups 1, 2 and 3. Each count pertains to its named group, not automatically to a distinct, non-overlapping set of volunteers. The design description specifically says that Group 3 volunteers came from Group 1. Consequently, the group denominators should be interpreted separately unless the registry record supplies a participant-level accounting that establishes otherwise. Such an accounting is not reported in the registry record.

The full enrollment was 24, but that number should not be substituted for the denominators in the adverse-event summaries. Enrollment and outcome-specific risk sets can differ because the record may summarize different groups or follow-up experiences. The registry record does not provide enough detail to reconcile all enrolled participants with the group-specific safety counts or to determine precisely how each participant contributed to each summary.

Why is the design important for analysis?

In a randomized comparison, allocation is intended to make treatment groups comparable on average with respect to measured and unmeasured factors. That principle does not apply in the same way to this non-randomized sequential design. Recruitment into Group 2 depended on how many volunteers completed Group 1, while Group 3 involved additional vaccination and another challenge among volunteers from Group 1. The group counts therefore reflect different study pathways, not parallel randomized arms.

Open-label conduct means masking was not used, according to the registry. General statistical explanation: lack of masking can matter for outcomes involving participant reports or investigator assessment because knowledge of group or treatment may affect reporting or classification. The registry record does not report procedures that might reduce such effects, nor does it describe blinded event adjudication. Those details are not reported in the registry record.

How should uncertainty be understood?

General statistical explanation: every estimate from a finite group is subject to sampling uncertainty. A confidence interval is a range of values generated by a method intended to reflect that uncertainty; it is not a guarantee that the true value falls within the particular interval. Small denominators generally make estimates less precise, particularly for uncommon events. This matters when reading zero event counts: a zero observed count does not establish that the underlying event probability is zero.

No confidence intervals or formal hypothesis tests for the adverse-event summaries are reported in the registry record. There is also no reported adjusted effect estimate or comparator-based estimate in the information available for this analysis. The event counts should therefore remain descriptive. The registry record does not report a statistical model for analyzing the safety endpoint.

What do the planning assumptions describe?

The record includes a planning illustration based on an observed effect, rather than the trial's own design justification. It specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. For time-to-event illustrations, the stated quantity is total events; for other outcomes, it is participants per arm. These assumptions describe a hypothetical planning exercise, not the design actually used in this non-randomized sequential trial.

General statistical explanation: a sample-size calculation estimates how many observations might be needed to detect a chosen effect under stated assumptions. It does not describe the study's observed results, and it is not observed power. A calculation based on an observed effect is especially unsuitable as a retrospective claim that the trial had a particular chance of detecting an effect, because the observed effect itself can be imprecise. The registry record does not report a prospective sample-size justification or the assumptions used when the trial was designed. Any planning illustration should therefore be kept separate from conclusions about the trial's actual design or evidential strength.

One analysis is recorded, but the statistical method, analysis population and handling of missing observations are not described in the registry record. The number of listed outcome measures does not establish how many were tested together, how analyses were prioritized, or whether adjustments for multiple testing were used. Those procedures are not reported in the registry record.

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("Group 1", "Group 2", "Group 3")
n      <- c(12, 4, 5)
events <- c(0, 0, 0)
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  Group 1  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7
ARM  Group 2  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Group 3  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and records one analysis. The available information does not explain how the outcomes were prioritized in analysis, whether all were analyzed, or whether the analysis was adjusted for multiple comparisons. A multiplicity procedure is not reported in the registry record.

General statistical explanation: when many outcomes or comparisons are examined, the chance of finding at least one apparently unusual result can increase, even if no true difference exists. Methods that control or describe this issue can make interpretation more transparent. The number of listed outcomes alone does not establish that a multiplicity problem occurred, but the lack of a reported analysis strategy means readers cannot determine whether or how it was addressed.

The registry record does not report a statistical analysis plan, an intention-to-treat population, a per-protocol population, or another defined analysis population. It also does not report how missing outcome data, incomplete follow-up, withdrawals, or participants who did not complete planned vaccinations or CHMI were handled. Those details are not reported in the registry record.

These omissions matter because the group descriptions are conditional on completion and sequential recruitment. The record says that Group 2 recruitment depended on Group 1 completion, and that Group 3 consisted of volunteers from Group 1 who received an additional dose and a second challenge. Without participant-level accounting and stated analysis rules, it is not possible to determine how incomplete participation affected inclusion in each outcome summary.

General statistical explanation: missingness can affect an estimate when the probability that an outcome is unobserved is related to the outcome itself or to participant characteristics. Different assumptions about missing observations can lead to different conclusions. Since the registry record does not describe missing-data methods, no assumption about such methods should be attributed to the trial.

12. 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 non-serious adverse event terms

The serious adverse-event counts are 0 of 12 at risk in Group 1, 0 of 4 in Group 2, and 0 of 5 in Group 3. Deaths are recorded as 0 for each group. These figures describe the events recorded in each group-specific safety summary; they do not establish that no serious event could occur outside the observed participants or follow-up.

The counts for other adverse events are 8 of 12, 3 of 4, and 2 of 5 for Groups 1, 2 and 3, respectively. The registry does not define these counts as grade 3 events, and they should not be treated as equivalent to the primary endpoint. The primary endpoint includes grade 3 solicited or unsolicited events within 28 days after vaccination as well as serious adverse events throughout the study. A separate count of participants meeting that complete definition is not reported in the registry record.

These group counts are not a head-to-head safety comparison. The study was non-randomized and sequential, and Group 3 participants were drawn from Group 1 for an additional vaccination and challenge. The summaries also do not report event types or participant-level overlap. The registry record lists no serious adverse-event terms. More detailed information about severity, timing, duration, relatedness, and follow-up is not reported in the registry record.

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

The registry supports a limited description of safety reporting: no serious adverse events or deaths are recorded in the group-specific summaries, while other adverse events were recorded among participants in each group. These counts concern the trial participants and the recorded group denominators. They do not establish the frequency of events in a wider population, and they do not by themselves quantify how risk would differ under another treatment or no vaccination.

The record does not report a complete result for the defined primary safety endpoint. Specifically, it does not provide a single reported count for participants with a grade 3 solicited or unsolicited event within 28 days after vaccination or a serious adverse event throughout the study. The separate serious-event counts address only one component of that definition. The other-event counts are not enough to determine which participants met the grade and timing criteria.

The trial's title and objectives include immunogenicity and efficacy, and the listed secondary outcomes include antibody and cellular responses and PMR-related measures. However, results for those outcomes are not reported in the information available for this analysis. No conclusion about immune response, parasite multiplication, protection, or efficacy can be drawn from the posted safety counts.

Nor can these data establish a causal difference between groups. Participants were not randomized, the study was open-label, and the groups followed different pathways. Group 2 recruitment depended on completion in Group 1, and Group 3 involved a selected subset receiving an additional dose and a second CHMI. Group contrasts may reflect these design features and other differences, rather than an intervention effect.

General statistical explanation: absence of a recorded event in a finite group is not evidence that the event is impossible. The strength of any safety conclusion depends on the number of participants, the completeness of follow-up, the event definitions, and how events were collected and analyzed. The registry record does not report enough detail to assess all of those features. The appropriate reading is therefore descriptive and bounded by the recorded groups, not a broad claim of safety or efficacy.

14. Why This Trial Matters Statistically

This trial illustrates why study design and outcome definition matter alongside the observed counts. A safety count can be easy to read, but its meaning depends on the endpoint criteria, its time window, and the group denominator. Here, the primary endpoint combines two types of events: grade 3 solicited or unsolicited events during a specified post-vaccination window, and serious adverse events throughout the study. A serious-event summary alone does not represent the whole endpoint.

The sequential structure also shows why group labels do not automatically imply comparable arms. Group 2 recruitment depended on completion in Group 1, while Group 3 was drawn from Group 1 for an additional dose and challenge. Such design features are essential context when interpreting separate counts. They prevent a simple reading of between-group differences as if they came from randomized allocation.

General statistical explanation: a study can be informative without being designed to estimate a comparative treatment effect. Early clinical research can describe how a candidate was administered and what events were recorded in the participants enrolled. But descriptive observations and causal comparisons answer different questions. Clear separation of those aims helps prevent a safety count from being mistaken for evidence about efficacy.

The registry record also makes visible the distinction between trial planning and retrospective planning illustrations. A calculation using an observed effect and stated assumptions is not the same as a prospective sample-size justification. It cannot substitute for a reported analysis plan or be interpreted as observed power. In this record, the design justification and statistical analysis plan are not reported in the registry record.

Finally, the absence of detailed reported results is itself important for statistical interpretation. Without an endpoint-level result, uncertainty estimate, analysis population, or missing-data approach, readers cannot assess the precision or robustness of findings beyond the posted counts. Recognizing what is and is not documented is a central part of interpreting a clinical trial record responsibly.

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 available registry information does not include a full primary endpoint result, even though it defines the endpoint as a participant count. The serious adverse-event summaries cover only one component of that definition; the separate other-event counts do not establish how many participants had a qualifying grade 3 event during the specified window. As a result, the principal safety outcome cannot be reconstructed from these summaries.

The group-specific safety denominators are not a set of clearly independent groups. Group 3 is described as a subset of Group 1, but the registry record does not give participant-level data showing how individuals contributed to each summary. Group 2's description is also incomplete. These features limit any attempt to reconcile the group counts with total enrollment or to compare the summaries.

The non-randomized, open-label, sequential design does not support a straightforward treatment-versus-control interpretation. Group membership and procedures differed, and no randomized control group is recorded. The registry record does not report adjustment methods that could address measured differences, nor would such methods by themselves remove all limitations of a non-randomized comparison.

Detailed event information is not reported in the registry record, including the nature of the other adverse events, their duration, timing beyond the endpoint windows, severity distribution, or assessed relationship to vaccination. The registry record also does not report a statistical analysis plan, outcome-level uncertainty estimates, missing-data methods, or defined analysis populations.

Finally, the record does not report the immunogenicity or parasite-related outcome results in the information available for this analysis. The lack of those results, together with the limited safety detail, means the posted information supports only a narrow descriptive reading. It does not support a comprehensive assessment of efficacy, immune response, or safety across a broader population.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1 — NCT04201431.
• Registry record last updated 2024-11-25; status last verified 2022-09.
• Results first posted 2024-11-25.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed, open-label, non-randomized, sequential Phase I/IIa trial of PvDBPII/Matrix-M1 in healthy adults living in the UK. Enrollment was 24. The primary endpoint was a participant count for grade 3 solicited or unsolicited adverse events within 28 days after vaccination or serious adverse events during the study.

Group-specific summaries record no serious adverse events and no deaths in Groups 1, 2 and 3. Other adverse events are recorded in each group. These are descriptive counts, not a randomized comparison, and Group 3 was drawn from Group 1 for an additional dose and challenge.

The registry record does not report the complete primary endpoint result, efficacy or immunogenicity results, a statistical analysis plan, missing-data methods, or analysis populations. The available counts therefore support a limited description of recorded safety events, not conclusions about comparative effects or efficacy.