A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG (NCT03330197), a non-randomized phase 1, phase 2 study. The primary outcome is The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance..

2. Clinical Question

3. Trial Design

This was a Phase I/II study of Ad-RTS-hIL-12 with oral veledimex in pediatric subjects with brain tumors, including DIPG. The registry lists Alaunos Therapeutics as the sponsor, an enrollment of 6, a start date of 2017-09-26, and a primary completion date of 2021-09-10. The study status is terminated. The reason for termination is not reported in the registry record.

The registry classifies the study as nonrandomized, with no masking and a single-group model. The intervention descriptions nevertheless distinguish two arms. Arm 1, marked closed, involved freehand intratumoral Ad-RTS-hIL-12 injection after tumor resection and oral veledimex in pediatric patients with brain tumors. Arm 2, marked open, involved stereotactic intratumoral injection and oral veledimex in pediatric patients with DIPG. The record does not report the allocation procedure or explain the arm status changes.

Because assignment was not randomized and the arms addressed different populations and injection approaches, a direct arm-to-arm contrast would not provide a like-for-like control comparison. The posted summaries are best read as descriptive observations from a small, nonrandomized study, not as evidence from a randomized comparative trial. The registry record does not report a control treatment, masking procedures, or a statistical plan for comparing the arms.

The primary objective was to evaluate safety and tolerability. Secondary outcomes included veledimex measurement in blood and brain tumor, overall survival, immune response measures for IL-12 and IFNg, adverse events assessed using CTCAE v5.0, best overall response by iRANO criteria, and duration of response. The record lists these outcome areas but does not report their results in the registry record for this analysis.

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: All subjects in Arm 1 received 10mg daily of veledimex. A total of three subjects were assigned to Arm 2. One subject withdrew consent prior to any study procedures on Day 0 and received no treatment. A second subject was discontinued from the study due to a Serious Adverse Event (SAE) after the Ad-RTS-hIL-12 injection but prior to receiving veledimex. The third subject received veledimex at a dose of 5 mg/day, which was the body surface area (BSA)-adjusted dose.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) or the OSP includes every subject who received at least one dose of any study drug recorded in the Data Management (DM) database excluding screen failures. • The data analysis for Adverse Events or other Safety variables will be performed on the OSP.

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: The baseline population includes every subject who received at least one dose of any study drug recorded in the Data Management (DM) database excluding screen failures. One patient in arm 2 withdrew consent prior to dosing and is considered a screen failure and one patient in Arm 2 only received Ad-RTS-hIL-12 (veledimex was not administered due to a serious adverse event.

6. Primary Endpoint

The registry lists the primary outcome as The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance., measured over From Day 0 through Day 56.

The primary endpoint concerns the safety and tolerability of intratumoral Ad-RTS-hIL-12 with veledimex, measured by dose-limiting toxicities (DLTs) and compliance. It is expressed as a count of participants. The stated assessment timeframe is Day 0 through Day 56, while the DLT criteria specifically apply to events during the first 28 days, from Day 0 to Day 28. The registry record does not report the number of participants meeting the endpoint or define how compliance was assessed.

The DLT definition combines several clinically important types of events: local reactions requiring operative intervention or urgent intervention; qualifying non-hematologic or hematologic toxicities; and specified exceptions for nausea and vomiting and transient neurological changes. The criteria include severity, attribution, and duration conditions for some events. For example, a Grade 3 or higher non-hematologic adverse event must be at least possibly related to study drug and last at least 3 days. Grade 4 hematologic toxicity, other than thrombocytopenia, must be at least possibly related and last at least 5 days. Transient neurological changes expected in Arm 2 are not considered a DLT unless they last > 10 days.

General statistical context: an early safety endpoint can help describe whether important toxicities arise during a defined observation period. It is not, by itself, a measure of comparative benefit. Here, the record gives endpoint definitions but not a primary endpoint result, so the endpoint cannot be quantified from the registry information described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the study as nonrandomized and single-group, with no masking. These design features determine what can be learned from the posted summaries. Without random assignment to a control condition, differences between groups may reflect differences in participants, tumor types, procedures, or other factors, rather than a treatment effect. In this study, the two arm descriptions refer to different populations and injection approaches, so they are not a like-for-like control comparison.

The primary endpoint is a count of participants meeting safety and tolerability criteria, including DLTs and compliance. The registry provides detailed DLT criteria but does not report the primary endpoint count. A count is a descriptive measure: it records how many participants met the endpoint definition. To interpret such a count as a rate, one also needs a clearly defined denominator and analysis population. The safety population is described as the FAS or OSP: subjects who received at least one dose of any study drug, excluding screen failures. The record says safety and other safety-variable analyses were to use the OSP.

General statistical context: a confidence interval expresses uncertainty around an estimate, rather than only presenting a single value. For a proportion, it can indicate how compatible a range of underlying event frequencies is with the observed data and the statistical method. Small samples generally produce wide uncertainty intervals, so point estimates alone can give an overly certain impression. The registry record does not report confidence intervals for the adverse-event summaries or the primary endpoint.

The posted adverse-event information separates serious events from other events and gives, for each arm, participants at risk, participants affected, and deaths. These categories should remain distinct. “At risk” indicates the listed group size for that summary; “affected” is a participant count, not necessarily a count of separate event episodes. A participant may have more than one event, and the registry record does not provide enough detail to reconstruct event-level counts or timing. Deaths are listed separately and should not automatically be assumed to be caused by study treatment.

The serious-event terms hydrocephalus and seizure are accompanied by percentages, but the record does not state the denominator or calculation basis for those percentages. The percentages therefore cannot be safely converted into counts or compared with percentages from another population. They describe the registry’s term summaries, not a fully specified incidence analysis.

General statistical context: over-dispersion is relevant when a count model assumes less variability than the data show; it can lead to uncertainty estimates that are too narrow if not addressed. The primary endpoint in this study is specified as a participant count, and the registry record does not describe a count-model analysis or report a dispersion estimate. There is no basis in the record to claim that over-dispersion was tested or adjusted for.

The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record does not report a sample-size justification for the trial itself. Any sample-size values from such an illustration are planning quantities, not observed power, and do not change the interpretation of the six-person enrollment or the nonrandomized design.

The registry reports no analyses in the registry record described. It does not report model specifications, hypothesis tests, confidence intervals, adjustment for covariates, or interim analyses. General statistical context: an inferential test addresses compatibility between data and a specified statistical model; it does not by itself establish causation or clinical importance. Without a reported analysis plan and results, there is no basis to infer which tests, if any, were used beyond the descriptive summaries.

The endpoint definitions use attribution and severity criteria, including whether an event was at least possibly related to study drug. Those criteria guide endpoint classification, but they do not prove that a reported event was caused by treatment. The registry record does not provide participant-level narratives or adjudication details. Interpretation must therefore stay with the posted definitions and aggregate counts.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcome areas, including veledimex measurements, overall survival, immune response, adverse events, best overall response, and duration of response. Considering multiple outcomes raises a general statistical issue: the more comparisons or tests made, the greater the chance that at least one result may appear noteworthy by chance alone. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical analysis plan explaining how multiple outcomes were to be interpreted. No inferential analysis results are reported in the registry record described.

Missing-data handling is not reported in the registry record. The record does not explain how missing endpoint assessments, incomplete follow-up, or unavailable laboratory measurements were handled. It also does not report whether participants who discontinued study treatment continued to contribute outcome data, or how death affected analysis of the other listed outcomes. These details matter because the amount and pattern of missing information can affect both the populations represented and the interpretation of outcome summaries.

The safety analysis population is defined as the FAS or OSP, consisting of every subject who received at least one dose of any study drug, excluding screen failures. Safety and other safety-variable analyses were to use the OSP. The record does not report the number in that population separately from the enrollment figure, nor does it describe analysis populations for the secondary outcomes. Therefore, the exact denominator for each outcome cannot be assumed from enrollment alone.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hydrocephalus (50.0%), seizure (33.3%).

The posted safety summaries report counts separately for Arm 1 and Arm 2. Arm 1 lists 3 participants at risk and 1 affected by serious adverse events, 3 at risk and 3 affected by other adverse events, and 2 deaths. Arm 2 lists 2 at risk and 1 affected by serious adverse events, 2 at risk and 2 affected by other adverse events, and 1 death. These are participant counts as represented in the registry summaries, not estimates from a comparative statistical model.

Hydrocephalus at 50.0% and seizure at 33.3% are listed as the top serious adverse-event terms. The denominator and calculation basis for these term percentages are not reported in the registry record. The percentages should not be read as arm-specific rates or used to infer how many participants experienced each term.

General statistical context: serious adverse events and deaths are important safety observations, but a count alone does not establish timing, severity beyond the category, relationship to study treatment, or cause. The registry record does not report enough detail in these summaries to determine those features. The arm counts should not be compared as if the arms were randomized control groups; they involved different populations and injection approaches.

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

The posted information documents a nonrandomized Phase I/II study of intratumoral Ad-RTS-hIL-12 with oral veledimex in pediatric subjects with brain tumors, including DIPG. It records an enrollment of 6 and gives descriptive safety summaries by arm. Those summaries include counts of participants at risk and affected by serious and other adverse events, deaths, and percentages for two top serious adverse-event terms.

The registry record does not report the primary endpoint result. It therefore does not show how many participants met the DLT definition or how compliance contributed to the endpoint. Nor do the listed secondary outcome areas supply results for survival, immune response, tumor response, duration of response, or drug measurements in the registry record described. The record’s terminated status is noted, but the reason for termination is not reported in the registry record.

The summaries do not establish whether any event was caused by study treatment. They also cannot establish a treatment effect, because there was no randomized control group and the arms were not like-for-like comparisons. The small enrolled population and limited descriptive information constrain precision and generalizability. No confidence intervals or inferential analyses are reported to quantify uncertainty.

General statistical context: a descriptive count answers how many participants were recorded in a category, while a comparative analysis requires a suitable comparison and assumptions that support the contrast. Even a carefully calculated statistical result cannot resolve design limitations such as nonrandom assignment or materially different groups. The reported information is therefore best understood as a limited safety description, not a definitive estimate of treatment benefit, harm, or comparative performance.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and reporting shape what can be concluded from an early-phase clinical study. The registry identifies a safety-focused primary objective, defines DLT criteria, and describes the intended safety population. Those elements make clear what the investigators intended to assess, even though the primary endpoint result is not reported in the information described.

The record also illustrates the distinction between a study’s enrollment and the denominator for a particular analysis. Safety analyses were to use the OSP, defined by receipt of at least one dose and exclusion of screen failures. Enrollment alone does not establish the population contributing to every reported outcome, and the record does not separately report all outcome-specific denominators.

The presence of two arm descriptions does not make the study a randomized comparison. One arm involved pediatric brain tumor patients after resection and freehand injection; the other involved pediatric patients with DIPG and stereotactic injection. Because allocation was nonrandomized and the groups differed in their described context, arm-specific counts are descriptive rather than evidence of relative treatment performance.

General statistical context: a transparent account of the endpoint, analysis population, missing-data approach, and uncertainty helps readers assess the scope of a result. Here, the endpoint definition and population description are available, but the record does not report the primary result, missing-data methods, confidence intervals, multiplicity approach, or detailed analysis plan. That contrast emphasizes why design information and complete results are both needed for sound statistical interpretation.

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.

Important limitations specific to this study include the nonrandomized design, the small enrollment of 6, and the absence of a like-for-like control group. The registry describes two arms that differ in population and injection approach, so arm-level counts cannot be interpreted as a controlled treatment contrast. The record does not report an adjustment strategy for differences between arms.

The study status is terminated, but the reason for termination is not reported in the registry record. The primary endpoint definition is available, but its result is not reported. The registry also does not report compliance results, confidence intervals, inferential analyses, or the detailed statistical plan. Missing-data methods and outcome-specific analysis populations are not reported.

The adverse-event summaries give aggregate participant counts, but the information described does not establish event timing, participant-level histories, or causal attribution. The denominator and calculation basis for the percentages attached to hydrocephalus and seizure are also not reported. The listed secondary outcomes do not have results in the registry record described, limiting interpretation beyond the safety summaries.

These limitations mean the posted results should be treated as descriptive and incomplete. They do not support firm estimates of event risk, comparisons between the arms, or conclusions about efficacy. General statistical context: estimates from small studies are inherently uncertain, and an observational contrast between nonrandomized groups may be confounded. The registry record does not report enough analysis detail to quantify or resolve those concerns.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG — NCT03330197.
• Registry record last updated 2025-08-12; status last verified 2025-08.
• Results first posted 2025-08-12.
• 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

The registry record describes a Phase I/II, nonrandomized study of intratumoral Ad-RTS-hIL-12 with oral veledimex in pediatric subjects with brain tumors, including DIPG. It lists an enrollment of 6, no masking, a single-group model, and two arm descriptions with different injection approaches and populations. Alaunos Therapeutics is listed as sponsor. The study began on 2017-09-26, had a primary completion date of 2021-09-10, and is marked terminated.

The primary objective was safety and tolerability, assessed by DLTs and compliance. The DLT timeframe is the first 28 days, within an overall primary endpoint timeframe from Day 0 through Day 56. The record defines the safety population as subjects receiving at least one dose, excluding screen failures. It reports descriptive adverse-event counts and identifies hydrocephalus and seizure among the top serious-event terms. The primary endpoint result, reason for termination, missing-data approach, and detailed statistical analysis plan are not reported in the registry record.