IPV-102 Safety, Tolerability and Immunogenicity of TAK-195 in Healthy Infants, Toddlers and Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IPV-102 Safety, Tolerability and Immunogenicity of TAK-195 in Healthy Infants, Toddlers and Adults (NCT03092791), a randomized phase 1, phase 2 study. The primary outcome is Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After First Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 1.

2. Clinical Question

The trial was designed to help select an antigen dosage of a stand-alone trivalent Sabin-based inactivated poliomyelitis vaccine (sIPV) for further study. Its stated objective was to compare three sIPV study arms using safety and tolerability after each primary immunization dose and immune responses to poliovirus types 1, 2 and 3 for both Sabin and Salk strains after the final dose of the primary series on Day 85.

The primary endpoint specified in the registry concerns a narrower question: the percentage of participants in the infant dose-ranging sIPV arms with solicited local reactions during the 7-day period after the first primary immunization dose on Day 1, classified by severity. This endpoint describes reactions reported at the injection site. It is not itself a measure of immune response, and the registry record does not give its numerical results.

The registry record describes the trial as randomized, double-masked and parallel. It does not report the reason the trial was terminated, the results for immune responses, or the numerical results for the primary endpoint.

3. Trial Design

NCT03092791 is recorded as a randomized Phase 1/2 parallel trial sponsored by Takeda. Its official title describes an observer-blind trial, while the registry’s masking classification is double. It enrolled 340 participants and is listed as terminated. The recorded study start was 2017-06-07, and the primary completion date was 2018-04-03. The reason for termination is not reported in the registry record.

The design included an age-step-down lead-in and an infant dose-ranging cohort. Adults received high-dose sIPV or placebo on Day 1. Toddlers received high-dose sIPV or reference IPV on Day 1. In the infant cohort, low-, medium- and high-dose sIPV, as well as reference IPV, were scheduled on Days 1, 29, 57 and 365. The registry identifies the trial condition as poliomyelitis and describes the participants as healthy.

The sIPV dose descriptions list antigen quantities for poliovirus types 1, 2 and 3. The low-dose formulation contained 0.75, 25 and 25 D-Ag units; the medium-dose formulation contained 1.5, 50 and 50 D-Ag units; and the high-dose formulation contained 3, 100 and 100 D-Ag units. The stated route was intramuscular injection. Reference IPV and placebo are listed as separate interventions.

The registry’s stated dose-selection objective combined safety and tolerability information after each primary immunization with immune-response measures after the third primary dose on Day 85. The listed primary endpoint, however, is a local-reaction measure after the first dose in infants receiving sIPV. These are related but distinct trial questions: the stated broader objective includes immunogenicity and repeated-dose safety, while the named primary endpoint focuses on solicited local reactions after an initial dose.

The registry record lists 34 outcome measures and zero analyses. It does not report a detailed statistical analysis plan, the reason for termination, or a sample-size justification. The planned booster dose on Day 365 appears in the infant schedules, and the listed secondary outcomes include safety assessments after booster vaccination.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Healthy participants were randomized to one of two (adult and toddler lead-ins) or four (infant dose ranging) arms in a 1:1 or a 1:1:1:1 ratio, to receive sIPV or reference sIPV. Two groups received placebo.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Set in 'Infant Dose Ranging Cohort - sIPV arms' included all participants who received at least one dose of the trial vaccines. Number analyzed is the number of participants with data available for analysis at the given timepoint.

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: All randomized participants.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Solicited Local Reactions Within 7-day Period (Including Day of Vaccination) After First Primary Immunization Dose of sIPV in Infant Dose Ranging Cohort by Severity on Day 1, measured over Within 7 days of the First Dose given on Day 1.

The primary endpoint is the percentage of participants in the infant dose-ranging sIPV arms with solicited local reactions within the 7-day period, including the vaccination day, after the first primary immunization dose on Day 1. Local reactions were recorded at the injection site using participant diary cards. The solicited events were pain, erythema, induration and swelling, with results classified by severity.

The registry describes pain categories according to interference with daily activity: mild pain does not interfere, moderate pain interferes with or without treatment, and severe pain prevents daily activity with or without treatment. For erythema, induration and swelling, the record describes size categories in millimetres, from any reaction below 25 mm through severity bands extending above 100 mm. It states that data are reported only for categories with at least one participant.

Solicited local reactions are collected in a defined observation period, which makes the endpoint a structured measure of short-term reactogenicity. Reporting severity can distinguish reactions that differ in their effect on daily activity or in their measured size. These features make the endpoint relevant to the trial’s stated safety and tolerability assessment, but it does not establish the cause of a reaction or describe immune response.

The registry record does not report the endpoint’s numerical values, category-specific denominators, or a statistical comparison. It therefore does not allow the frequency or precision of local reactions to be assessed from the record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-masked, parallel Phase 1/2 trial. Randomization is a method for assigning participants to study groups by chance. In general, it can reduce systematic differences between groups at the start of a trial, although random assignment does not guarantee that groups will be identical. A parallel design means that groups receive their assigned study intervention rather than crossing over between interventions. The record also calls the trial observer-blind in its official title; further details about who was masked and how masking was maintained are not reported in the registry record.

What does a percentage endpoint represent?

For a binary event outcome, a percentage describes the number of participants meeting the event definition relative to the number assessed for that outcome. The endpoint is the percentage with solicited local reactions after the first dose, reported by severity category. A percentage is most interpretable when its numerator, denominator, event definition and observation period are clear. The registry specifies the event types and the 7-day window, but it does not report the numerical primary endpoint results or the category-specific counts and denominators.

Because the endpoint is organized by severity and includes several types of local reaction, a single overall figure would not preserve all the detail in the outcome definition. The registry says only categories with at least one participant are reported. This means an omitted category cannot be interpreted as a reported zero unless the record explicitly gives that result. No such category-level primary outcome values are included in the record.

Why do denominators matter?

The denominator for a result is the number of participants with data available for the relevant outcome and time point, rather than automatically the number enrolled in a group. The primary outcome description says that the number analyzed is the number of participants with data available at the given time point. As a general statistical principle, differences in availability can affect how group percentages should be compared. The registry does not give the primary endpoint denominators, missing-data counts, or an account of how missing observations were handled.

How should uncertainty be evaluated?

In general, a confidence interval describes a range of values compatible with the observed data under a specified statistical method. It helps distinguish the precision of an estimate from the estimate itself. A narrow interval indicates greater precision than a wide interval, while an interval that spans a range of plausible effects may leave the comparative result uncertain. The registry record does not report confidence intervals or other uncertainty estimates for the primary endpoint, so its precision cannot be assessed from this record.

For event outcomes, comparisons can also be affected by sparse data. When event counts are small, estimates may be imprecise and methods based on large-sample approximations may be less dependable. General methods can account for this in different ways, but the approach used for the trial is not reported in the registry record. The safety counts should therefore be read descriptively rather than as a substitute for a prespecified comparative analysis.

What does multiplicity mean in this setting?

Multiplicity arises when a study evaluates many outcomes, groups, time points or contrasts. Each statistical test can create an opportunity for a result to appear notable by chance; considering many tests together can increase that opportunity. A multiplicity strategy may define a primary comparison, adjust significance thresholds, or organize tests in a hierarchy. These are general options, not claims about this trial. The registry lists 34 outcome measures and zero analyses, and a multiplicity strategy is not reported in the registry record.

The trial’s objective covers multiple vaccine doses, poliovirus types and strains, safety assessments and time points. That broad scope makes it important to know which comparisons were planned as confirmatory and how they were to be interpreted. The registry does not report those details. No unadjusted or adjusted inferential results for the primary endpoint are included in the record.

What do planning calculations mean?

General sample-size planning asks how many participants may be needed to detect an effect under stated assumptions. The planning assumptions described for illustrative calculations use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the target effect is expressed as a stated fraction of an observed effect. These are planning illustrations, not the trial’s own design justification and not observed power. The registry record does not report the trial’s sample-size justification or its statistical plan. Planning estimates cannot fill in the unreported primary results or establish what the trial was able to detect.

Over-dispersion is a general issue for count data when variability exceeds what a simple model assumes. Allowing for it can change uncertainty estimates and statistical tests. It is not possible to determine from the registry record whether over-dispersion was relevant to any analysis in this trial or whether a method addressing it was used. More generally, the registry provides outcome descriptions and selected safety counts but not enough analysis detail to reconstruct the intended inference.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 34 outcome measures and zero analyses. The outcome list spans safety and tolerability assessments, several observation periods, primary and booster vaccination, and immune-response aims described in the trial summary. When many outcomes, groups or time points are considered, multiplicity can make chance findings more likely across the full set of comparisons. A prespecified strategy can help define which results are primary and how secondary findings should be interpreted. Such a strategy is not reported in the registry record.

The primary endpoint description defines the population as the Safety Set in the infant dose-ranging sIPV arms: participants who received at least one dose of trial vaccine. It also says the number analyzed is the number with data available at the time point. These statements identify a safety-oriented population and a time-point-specific available-data denominator, but they do not explain how missing diary entries or other unavailable data were treated. Imputation, sensitivity analyses and reasons for missingness are not reported in the registry record.

The record does not provide the numerical primary outcome results, confidence intervals, test statistics or a statistical analysis plan. It therefore does not indicate whether the reported endpoint categories were compared inferentially, whether any adjustment for multiple testing was planned, or how analyses across doses and outcomes were prioritized. The record’s zero analyses entry should not be read as evidence that no analyses were conducted; it means analyses are not recorded in the registry information.

These gaps matter because a complete interpretation depends on more than an outcome definition. The analysis population, available-data rules, planned contrasts, missing-data handling and multiplicity approach all affect how estimates should be read. Their absence limits conclusions from the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (6.7%), gastroenteritis (3.4%), bronchiolitis (3.3%), bronchitis (1.7%), urinary tract infection (1.7%).

The registry lists serious adverse event counts separately for each cohort and arm. In the adult lead-in, the counts were 0 of 20 with high-dose sIPV and 0 of 20 with placebo. In the toddler lead-in, the counts were 0 of 30 with high-dose sIPV and 0 of 30 with reference IPV. In the infant dose-ranging cohort, the counts were 8 of 59 with low-dose sIPV, 5 of 60 with medium-dose sIPV, 5 of 60 with high-dose sIPV and 8 of 60 with reference IPV.

The death counts recorded were 0 in the adult and toddler arms, 1 in the infant medium-dose sIPV arm, 0 in the infant low- and high-dose sIPV arms, and 1 in the infant reference IPV arm. These are registry counts, not estimates of comparative risk or evidence of causation. The record does not report a statistical comparison of serious adverse events or deaths.

Other adverse event counts are also listed: 8 of 30 in the toddler high-dose sIPV group and 13 of 30 in the toddler reference IPV group; 17 of 59, 17 of 60, 19 of 60 and 20 of 60 in the infant low-dose, medium-dose, high-dose and reference IPV groups, respectively. Both adult groups are listed with 0 of 20. These entries should be interpreted using the registry’s categories and follow-up context; they do not, by themselves, establish whether events were related to vaccination.

The registry also lists serious-event terms with percentages, including pneumonia at 6.7%, gastroenteritis at 3.4%, bronchiolitis at 3.3%, and bronchitis, urinary tract infection and milk allergy at 1.7% each. The record does not provide enough detail alongside these terms to infer causation or compare treatment groups from them.

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

The record describes a randomized trial intended to evaluate safety, tolerability and immune response while selecting among three sIPV antigen doses. It identifies the cohorts, interventions, schedules and a primary endpoint focused on solicited local reactions after the first primary dose in infants. These details clarify what the investigators set out to study, but they are not themselves evidence of the endpoint’s observed results.

The registry contains descriptive safety counts for serious and other adverse events, as well as death counts by arm. Such counts are useful for understanding what the record reports, but they do not establish that an intervention caused an event or that one intervention differs from another. A causal or comparative interpretation would require suitable analyses and information about uncertainty, follow-up and the analysis population. Those comparative results are not reported for the primary endpoint in the registry record.

The record does not report numerical results for the primary local-reaction endpoint or the immune responses that were central to the stated dose-selection objective. It also does not explain why the trial was terminated. Consequently, it cannot establish which dose was selected, whether the prespecified objectives were met, or why the study stopped.

General statistical interpretation distinguishes an estimate from its precision and from the decision context in which it might be used. An observed percentage, when available, describes the data in its defined population and time window; an uncertainty interval would help convey how precisely it is estimated. Neither the primary endpoint estimate nor its uncertainty is present in the registry record. The trial’s stated purpose should therefore not be mistaken for a reported conclusion about dose selection.

The findings that can be stated are limited to the trial’s recorded design and the safety counts listed by cohort and arm. No conclusion that a vaccine does or does not work follows from these entries. The registry record does not report efficacy outcomes or the numerical immunogenicity comparisons needed to assess the stated immune-response objective.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining an age-step-down lead-in with infant dose-ranging. The lead-in cohorts involved adults and toddlers, while the infant cohort compared three sIPV dose levels with reference IPV. The schedules also differed across cohorts: the lead-in interventions were given on Day 1, while the infant interventions included doses on Days 1, 29, 57 and 365. Such features make it important to keep cohort-specific questions and denominators distinct rather than treating all arms as one interchangeable comparison.

The trial’s stated objective covered more than one kind of evidence. Safety and tolerability were assessed alongside immune responses to multiple poliovirus types and strains. The named primary endpoint, in contrast, concerns local reactions after the first dose in the infant sIPV arms. This illustrates a general design issue: a trial can have a broad scientific objective while a particular primary endpoint answers a narrower question. The registry record does not report the numerical results needed to connect that primary endpoint to the broader dose-selection objective.

The record also shows why clear reporting of analysis methods matters. It lists 34 outcome measures and zero analyses, while not reporting a statistical analysis plan, multiplicity strategy or missing-data approach. For a study with multiple cohorts, outcomes and time points, those details help readers distinguish planned comparisons from exploratory descriptions and understand how uncertainty should be interpreted.

Finally, the registry lists the trial as terminated without reporting the reason. That status is relevant context, but it cannot explain the missing outcome results or reveal whether termination affected the planned analyses. The record makes the trial’s intended structure visible while leaving important inferential and reporting questions unresolved.

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 main limitation for interpretation is that the registry record does not report numerical results for the primary endpoint. Although it defines local reactions, severity categories and the observation period, it does not give the category-specific counts, percentages, denominators or uncertainty estimates needed to assess the endpoint. The immune-response comparisons that formed part of the trial’s stated objective are also not reported.

The registry lists 34 outcome measures and zero analyses. A statistical analysis plan, including any prespecified contrasts or multiplicity approach, is not reported in the registry record. Nor are missing-data handling rules, sensitivity analyses, or details about how the available-data denominators varied across outcomes and time points. This limits the ability to assess the completeness and comparability of outcome reporting.

Safety information is available as counts by arm, but the registry record does not report statistical comparisons for those counts or provide an account of event attribution. Counts should therefore remain descriptive. The serious-event terms and percentages are listed without enough accompanying analysis detail to support causal interpretation or comparative claims.

The registry lists the trial as terminated but does not report the reason for termination. It also does not provide the detailed sequence of recruitment, follow-up completion or any consequences for the planned outcome assessments. These omissions prevent a determination of whether termination affected the availability of results.

Finally, the primary endpoint is confined to local reactions after the first dose in infants receiving sIPV, whereas the trial objective refers to repeated primary immunizations and immune responses after the final primary dose. The endpoint definition alone cannot answer all questions motivating the trial. The record’s limited numerical reporting prevents broader conclusions about dose selection.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: IPV-102 Safety, Tolerability and Immunogenicity of TAK-195 in Healthy Infants, Toddlers and Adults — NCT03092791.
• Registry record last updated 2020-01-31; status last verified 2020-01.
• Results first posted 2020-01-31.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03092791 was a randomized, double-masked, parallel Phase 1/2 trial sponsored by Takeda. It enrolled 340 healthy participants across adult and toddler lead-in cohorts and an infant dose-ranging cohort. The study is listed as terminated; the reason is not reported in the registry record.

The trial compared low-, medium- and high-dose sIPV with reference IPV in infants, with placebo included in the adult lead-in. The primary endpoint was the percentage of infants in the sIPV dose-ranging arms with solicited local reactions by severity within 7 days after the first primary dose. The broader stated objective also included safety, tolerability and immune responses after the three-dose primary series.

The registry lists 34 outcome measures and zero analyses. It reports selected adverse-event counts, but numerical primary endpoint and immunogenicity results, a statistical analysis plan, missing-data methods, multiplicity handling and the reason for termination are not reported in the registry record.