Efficacy of SJ733 in Adults With Uncomplicated Plasmodium Falciparum or Vivax Malaria: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of SJ733 in Adults With Uncomplicated Plasmodium Falciparum or Vivax Malaria (NCT04709692), a non-randomized phase 2 study. The primary outcome is Crude Adequate Clinical and Parasitological Response (ACPR).

2. Clinical Question

3. Trial Design

This was a Phase 2a, open-label, non-randomized study with sequential cohorts. Its official title describes assessment of efficacy, safety, tolerability, and pharmacokinetics of SJ733 with or without cobicistat over a 42 day period. The registry lists enrollment of 22 participants and a completed status. The recorded study start was 2021-04-14, and primary completion was 2022-04-15.

Participants with uncomplicated P. vivax and P. falciparum malaria were assigned to species-specific arms within three cohorts. Cohort 1 used 600 mg SJ733 with 150 mg cobicistat; cohort 2 used 600 mg SJ733 alone; cohort 3 used 300 mg SJ733 with 150 mg cobicistat. In each cohort, the same regimen was listed separately for vivax and falciparum malaria. Treatment was oral, once daily for three consecutive days. The registry lists SJ733 as the intervention and describes cobicistat as a pharmacoenhancer in the study summary.

Because allocation was non-randomized and sequential, comparisons between regimens can be influenced by differences in when participants entered the study or in the groups enrolled. The registry specifically warns that the arms are not a like-for-like control comparison. The open-label design also means treatment was not masked. Details of the cohort sequence, allocation decisions, or procedures intended to address potential differences between groups are not reported in the registry record.

The study included secondary outcomes on malaria signs and symptoms, parasite clearance, parasite reduction, and SJ733 pharmacokinetics. The registry lists 27 outcome measures but no analyses. The number enrolled in each arm, recruitment by species, and any participant flow information are not reported in the registry record. These omissions limit reconstruction of the actual analyzed groups from the overall enrollment alone.

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

Analysis population for the primary outcome, as defined in the registry: Only participants eligible for efficacy analysis were analyzed.

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.

6. Primary Endpoint

The registry lists the primary outcome as Crude Adequate Clinical and Parasitological Response (ACPR), measured over 14 days for each arm.

The primary endpoint was crude Adequate Clinical and Parasitological Response (ACPR), expressed as a percentage of participants. ACPR was defined as the absence of microscopically determined parasitemia on thick smear. The endpoint was assessed at 14 days for each arm, and the stated analysis population consisted only of participants eligible for efficacy analysis.

This endpoint combines a clinical-trial response label with a parasitological criterion: the specific definition recorded for this outcome is no detectable parasitemia by the stated microscopy method at the stated follow-up. It therefore represents a binary outcome for each eligible participant: parasitemia was absent or it was not absent at the assessment. Reporting the fraction or percentage meeting the definition can make the response frequency understandable across groups, provided the denominator and eligibility rules are clear.

As a general statistical point, a binary endpoint is useful when the research question concerns whether participants meet a prespecified response definition by a particular assessment time. It simplifies varied individual measurements into a defined outcome, but that also means it does not describe the full course of parasite clearance or the magnitude of any change before the assessment. The registry lists parasite clearance time, parasite reduction rate, and changes in asexual parasites among secondary outcomes, which address different aspects of response.

The registry record does not report the primary ACPR percentages, counts, confidence intervals, or a statistical comparison. It also does not report the detailed eligibility rules for efficacy analysis. Thus, the endpoint definition and timing are available, but the numerical primary outcome and the precision of its estimate are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: each eligible participant either met the ACPR definition at the assessment or did not. The registry expresses the outcome as a percentage of participants. For a binary outcome, the percentage describes how common the defined response was within the analyzed group. Its interpretation depends on knowing both the number meeting the definition and the number included in the analysis. Neither arm-specific ACPR counts nor percentages are reported in the registry record.

As a general statistical point, an estimate based on a small group can vary substantially from one set of participants to another. A confidence interval is a way to express uncertainty around an estimated response frequency. A narrower interval indicates greater precision under the assumptions of the method; a wider interval indicates less precision. The registry record does not report confidence intervals for ACPR, so the precision of the primary result cannot be assessed from the posted information.

The outcome timeframe is 14 days for each arm. A fixed-time binary response answers whether the endpoint definition was met at that assessment; it does not show how quickly an individual cleared parasites or describe measurements between assessments. The registry separately lists parasite clearance time, parasite reduction rate, asexual parasite clearance time, and percent change in asexual parasites from baseline. These outcomes concern different properties of response, and their numerical analyses are not reported in the registry record.

The study design affects how comparisons should be understood. Allocation was non-randomized, and the cohorts were sequential. Random allocation, as a general design principle, is intended to make groups comparable on average with respect to both measured and unmeasured characteristics. That protection is not established by the recorded design. The registry also warns that the arms are not a like-for-like control comparison. Differences between their outcome frequencies, if reported, could reflect differences in participants or cohort circumstances as well as regimen differences. No statistical adjustment or causal comparison method is reported in the registry record.

The trial was open label, with no masking. In general, awareness of treatment can influence participant reporting, clinical assessment, or decisions about follow-up, depending on the outcome and procedures. The primary endpoint uses microscopy, but the registry record does not describe whether laboratory assessment was masked or give further details of measurement procedures. It is therefore not possible to characterize safeguards against assessment knowledge beyond the stated open-label design.

The record lists 27 outcome measures and no analyses. Having multiple outcomes raises a general statistical issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase if each is judged separately. Methods that account for multiplicity may be appropriate depending on the analysis plan and the claims being made. The multiplicity approach, any prespecified hierarchy among outcomes, and the statistical tests used are not reported in the registry record. No particular inferential test should be assumed.

The sample-size note describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the illustration varies the effect to detect as a fraction of the observed effect. Such calculations are prospective planning scenarios, not observed power and not evidence that the trial had a particular probability of detecting an effect. The note also distinguishes event totals for time-to-event outcomes from participants per arm for other outcomes. Numerical planning results and the trial's own sample-size justification are not reported in the registry record.

As a general statistical point, over-dispersion occurs when observed variability exceeds what a statistical model assumes. It can make standard errors too small if the model does not account for the extra variability. The posted primary endpoint is binary, but the registry does not specify a model or report whether over-dispersion was relevant to any analyses. No model choice, diagnostic procedure, or correction can therefore be attributed to the study from the registry entry.

Pharmacokinetic outcomes include area under the plasma concentration-time curve, maximum plasma drug concentration, and time to maximum plasma concentration. In general, these describe exposure over time, peak concentration, and the timing of that peak, respectively. They address drug disposition rather than directly measuring ACPR. The registry lists these outcomes but does not report their numerical results or analysis methods.

Finally, a reported percentage can be difficult to interpret when participants have missing endpoint assessments or are excluded from an analysis. The primary population is described only as participants eligible for efficacy analysis. The eligibility criteria, missing-data handling, and sensitivity analyses are not reported in the registry record. This makes it impossible to determine from the entry how exclusions or unavailable assessments affected the primary estimate.

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("Arm 1 B (Cohort 1)", "Arm 2 B (Cohort 2)")
n      <- c(10, 9)
events <- c(9, 9)
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  Arm 1 B (Cohort 1)  10  9  90.0  55.5  99.7  59.6  98.2  58.7  97.7
ARM  Arm 2 B (Cohort 2)  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 27 outcome measures, including the primary ACPR endpoint and secondary outcomes covering symptoms, parasite clearance, parasite reduction, and pharmacokinetics. It records no analyses. A multiplicity strategy, such as a hierarchy of outcomes or an adjustment for multiple statistical tests, is not reported in the registry record. As a general statistical point, interpreting numerous outcome tests separately can increase the chance of finding an apparently notable result by chance. Without the analysis plan and results, the extent to which this issue applies to the reported findings cannot be assessed.

The primary outcome population is described as participants eligible for efficacy analysis. The criteria defining eligibility, the number meeting those criteria, and the handling of participants without an endpoint assessment are not reported in the registry record. It is also not reported whether analyses used all eligible participants, excluded particular observations, or examined alternative assumptions about missing outcomes. Consequently, the primary analysis denominator and the impact of missing data cannot be reconstructed.

For safety, the record lists groups for two falciparum cohorts, but it does not provide a complete participant flow across every study arm. The number of participants with available safety follow-up, the follow-up duration used for each safety summary, and the treatment of missing safety observations are not reported in the registry record. These details are needed to understand how representative the posted safety counts are of the full enrolled population.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile syndrome of probable viral etiology (10.0%), severe malaria grade 4 (8.3%).

The registry lists serious adverse event information for Arm 1 B (Cohort 1) and Arm 2 B (Cohort 2), both falciparum groups. For Arm 1 B, the record lists 10 participants at risk for serious adverse events and 1 affected; it lists 10 at risk for other adverse events and 2 affected. For Arm 2 B, it lists 12 at risk for serious adverse events and 1 affected; it lists 12 at risk for other adverse events and 3 affected. Deaths are listed as 0 in each group.

The listed serious-event terms include Febrile syndrome of probable viral etiology at 10.0% and Severe Malaria Grade 4 at 8.3%. These are registry entries, not evidence by themselves that a treatment caused the events. The record does not provide enough detail to assign each term to a specific participant or infer a causal relationship.

These figures cover only the two listed falciparum groups. Serious adverse event counts are not a complete description of all safety outcomes, and event counts are not interchangeable with the number of participants affected. The record does not report corresponding safety-group figures for the vivax arms or additional context such as event timing, duration, or attribution.

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

The registry record establishes that a completed Phase 2a study evaluated SJ733 regimens, with or without cobicistat, in adults with uncomplicated P. vivax or P. falciparum malaria. It describes the treatment schedules, the primary ACPR definition, and several secondary outcome domains. It also records selected safety counts for two falciparum groups. These registry entries describe the study's scope and recorded measures.

They do not establish the numerical primary response rate. The ACPR values and their denominators are not reported in the registry record. Thus, the posted entry does not permit an estimate of how many eligible participants met the primary endpoint in each arm, how precise any arm estimate was, or whether arm outcomes differed. It also does not permit an efficacy comparison between the regimen with cobicistat and the regimen without it.

Even if a difference between arms were available, the design would need to shape its interpretation. The study used sequential, non-randomized cohorts, and the registry warns that the arms are not a like-for-like control comparison. A simple difference in observed outcomes would not isolate the treatment effect from other differences between cohorts. The record does not report a statistical model or adjustment strategy that would address this issue.

The safety figures should be read as limited counts in two falciparum groups, not as a complete safety profile or a basis for attributing events to treatment. The registry does not report all safety results across the species-specific arms, and the serious event terms alone do not show causality.

More broadly, the listed secondary endpoints could add information about parasite clearance, symptoms, and drug exposure, but their numerical results are not reported in the registry record. The study's listed outcomes and completed status do not substitute for posted results. The appropriate interpretation is therefore constrained: the design and intended measurements are described, while the primary efficacy estimate, its uncertainty, and the full set of analyzed outcomes remain unavailable in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable as a small Phase 2a study with several related but distinct comparisons: two malaria species and three sequential regimens. That structure makes it important to keep species, dose, and cobicistat use distinct when reading any outcome. Combining groups could conceal differences, while comparing them as if randomized could overstate what the design supports. The registry itself cautions that the arms are not a like-for-like control comparison.

The primary endpoint is a clearly defined binary parasitological response at a fixed assessment time. That makes the outcome conceptually straightforward, but interpretation still depends on arm-level counts, denominators, and uncertainty estimates. Those numerical primary results are not reported in the registry record. The absence of posted analyses also means the reader cannot assess how the many listed outcomes were prioritized or tested.

The record includes outcomes beyond a single response percentage, such as parasite clearance measures and pharmacokinetic measures. Statistically, these represent different questions rather than interchangeable versions of the same endpoint. A response at 14 days, the time course of parasite clearance, and plasma drug exposure each describe a different aspect of the study.

The study also illustrates why design and results must be read together. Sequential non-randomized cohorts may be useful for evaluating regimens in an early-stage study, but they do not provide the same protection against group differences as randomized allocation. The record's limited result reporting further narrows what can be inferred: the design is documented, but the primary response estimate and its precision are not.

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 main trial-specific limitation for interpretation is the non-randomized, sequential design. The registry explicitly warns that the arms are not a like-for-like control comparison. As a result, arm differences cannot be attributed to regimen alone without additional design or analysis support, and the record does not report adjustment methods.

The open-label design means treatment was not masked. The registry does not say whether microscopy assessment was masked or provide enough procedural detail to evaluate possible effects of treatment knowledge on outcome measurement or follow-up. This uncertainty is separate from the objective-sounding endpoint definition itself.

Overall enrollment was 22, while six species-by-regimen arms are listed. The number of participants in each arm and each primary analysis group is not reported in the registry record. Without those counts, the scale and precision of arm-specific estimates cannot be assessed. The primary ACPR results, confidence intervals, and statistical comparisons are also not reported.

The registry lists 27 outcome measures but records no analyses. A prespecified analysis plan, multiplicity approach, missing-data procedures, detailed efficacy eligibility criteria, and sensitivity analyses are not reported in the registry record. It is therefore not possible to assess whether outcome reporting followed a planned hierarchy or how unavailable assessments were handled.

The safety information shown in the record covers two falciparum groups and does not give complete safety figures for all arms. The listed serious adverse event terms and group counts do not establish causation and do not replace a full safety summary. Finally, although the record describes pharmacokinetic and parasite-clearance outcomes, their numerical results and analysis methods are not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy of SJ733 in Adults With Uncomplicated Plasmodium Falciparum or Vivax Malaria — NCT04709692.
• Registry record last updated 2023-12-04; status last verified 2023-11.
• Results first posted 2023-12-04.
• 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 Phase 2a trial of SJ733 with or without cobicistat in adults with uncomplicated P. vivax or P. falciparum malaria. Enrollment was 22, and the study used sequential cohorts with three oral regimens administered once daily for three consecutive days. The primary endpoint was crude ACPR, defined as absence of microscopically determined parasitemia on thick smear at 14 days among participants eligible for efficacy analysis.

The record lists 27 outcome measures and no analyses. It provides selected adverse-event counts for two falciparum groups, while the primary efficacy values, arm-level analysis denominators, confidence intervals, and numerical secondary results are not reported in the registry record. The non-randomized design also limits direct interpretation of differences between cohorts.