A Safety, Tolerability, and Efficacy Study of VC-01™ Combination Product in Subjects With Type I Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety, Tolerability, and Efficacy Study of VC-01™ Combination Product in Subjects With Type I Diabetes Mellitus (NCT02239354), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Adverse Events Reported During the Study..

2. Clinical Question

The study was designed as a first-in-human evaluation of safety, tolerability, and efficacy in subjects with Type 1 Diabetes Mellitus. Its primary outcome measure was the number of adverse events reported through the Month 24 visit. That endpoint describes the event burden recorded over the stated follow-up period; it is not itself a measure of glycemic control or another efficacy outcome.

The record lists 19 enrolled participants, but its adverse-event summaries show participants at risk in Cohort 1 and none at risk in Cohort 2. The record therefore does not provide a basis for comparing adverse-event experience between the cohorts. Nor does the available result information establish whether the product achieved a particular clinical benefit. The question that can be addressed from the posted information is limited to what the registry reports about safety and the design used to collect that information.

3. Trial Design

This was a prospective, multicenter, open-label, first-in-human Phase 1/2 study with two sequential cohorts. Allocation was non-randomized, and masking was absent. The registry lists ViaCyte as the sponsor and Type 1 Diabetes Mellitus as the condition. Enrollment was 19. The study start is listed as 2014-09, primary completion as 2017-12, and status as terminated.

The intervention was VC-01™ Combination Product. Cohort 1 received 2 implants, while Cohort 2 received 4 or 6 implants. The record describes the study as testing whether the product could be implanted subcutaneously and maintained safely for two years, as well as testing its efficacy. The primary safety endpoint was the number of adverse events reported through the Month 24 visit.

Sequential enrollment means that the cohorts were not formed as concurrent randomized groups. Because allocation was non-randomized and the study was open-label, participant characteristics, treatment experience, observation, or other factors could differ between cohorts. The record does not report enough information to establish that the cohorts were comparable, and their adverse-event summaries cannot be treated as a controlled estimate of a treatment difference.

The registry record does not report the reason for termination, the detailed recruitment or implant schedule, or a statistical analysis plan. It also does not state whether every participant completed follow-up through the Month 24 visit. The listed primary-completion date is a registry date, not evidence by itself that each participant completed the planned observation period.

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: The Safety Analysis Set (SAS) will include all T1DM subjects who were enrolled into the study and in whom an implant surgery was attempted, regardless if any VC-01-250 units or sentinel-sized units were actually implanted. This includes all subjects in both Cohort 1 and Cohort 2.

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: Cohort 2 enrollment was never initiated and is therefore 'zero'.

6. Primary Endpoint

The registry lists the primary outcome as Number of Adverse Events Reported During the Study., measured over Thru the Month 24 Visit.

The primary endpoint is the number of adverse events reported during the study through the Month 24 visit. It is a count-based safety measure: it concerns how many events were reported, rather than only whether a participant experienced at least one event. A count may reflect repeated events in a participant, while a summary of participants affected answers a different question. The posted adverse-event summaries include affected-participant information, but a numerical result for the primary event-count endpoint is not reported in the registry record.

Safety endpoints are used in early clinical evaluation to describe unwanted medical events observed during exposure and follow-up. They can help characterize the types and frequency of events recorded in the study population. They do not, by themselves, establish that an intervention caused an event or that an event would occur at the same frequency in another population. In an open-label, non-randomized study, interpretation also depends on how events were collected, classified, and followed.

The stated Safety Analysis Set includes all Type 1 Diabetes Mellitus subjects enrolled in the study in whom implant surgery was attempted, regardless of whether any VC-01-250 units or sentinel-sized units were actually implanted. It includes both cohorts. This definition makes the attempted surgery, rather than successful implantation alone, the stated basis for inclusion in the safety population.

The registry record does not provide the primary endpoint’s numerical event count, an uncertainty interval, or a comparison estimate. The endpoint’s purpose and time frame are described, but its result cannot be reconstructed from the other adverse-event summaries.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count endpoint represent?

The primary endpoint is a count of adverse events, not a count of participants who experienced at least one event. In general, a participant may contribute more than one event to an event count. A participant-level affected count instead indicates how many participants had an event of the specified type. These measures answer different questions and should not be substituted for one another. In this registry record, the primary endpoint is described as an event count, while the displayed safety information includes affected-participant summaries. The record does not report the numerical result for the primary count endpoint.

General statistical context: count outcomes can have a distribution in which variability is greater than a simple count model assumes. This is called over-dispersion. It can arise, for example, when participants differ in their underlying event propensity or when events cluster within participants. If a formal count model is used, accounting for over-dispersion can affect uncertainty estimates. The registry record does not report a model for the primary endpoint or indicate whether over-dispersion was assessed, so no such method should be attributed to this study.

What does the safety population definition do?

The stated Safety Analysis Set includes enrolled subjects for whom implant surgery was attempted, whether or not any VC-01-250 units or sentinel-sized units were actually implanted. This rule defines who is included in the safety population. Including attempted procedures regardless of actual implantation can preserve information about events related to the procedure or the treatment process, but the registry does not explain the rationale for the definition or provide details about how events were attributed.

A defined analysis population is important because the denominator determines the population to which a summary applies. The definition does not imply that every participant had the same exposure, completed the same follow-up, or received the same number of implants. The registry describes different implant counts for the cohorts, and its posted adverse-event summary lists participants at risk by cohort. It does not report participant-level exposure duration or the completeness of follow-up.

Why does study design affect comparisons?

General statistical context: random allocation can help balance measured and unmeasured participant characteristics between groups, on average. In a non-randomized study, differences between groups may reflect treatment, selection, timing, baseline health, or other factors. Open-label conduct can also affect event observation and reporting. These considerations do not make descriptive safety information useless; they limit the strength of causal comparisons.

This study was non-randomized, open-label, and sequential. Its cohorts therefore are not equivalent to randomized treatment and control groups. Cohort 1 and Cohort 2 also differ in the number of implants described, and the adverse-event summary lists no participants at risk for Cohort 2. A between-cohort treatment effect cannot be estimated from the available summaries. The registry explicitly does not present the arms as a like-for-like control comparison.

How should uncertainty and significance be read?

General statistical context: a confidence interval expresses the range of estimates compatible with the observed data under a specified statistical method and assumptions. It communicates precision, not certainty that a particular value is true. A hypothesis test and its p-value address compatibility with a statistical null model; neither alone establishes clinical importance or causation.

The registry record does not report a confidence interval, p-value, or inferential analysis for the primary endpoint or the adverse-event summaries. No claim of statistical significance or precision can therefore be made from the posted information. A term percentage without an accompanying uncertainty estimate can be described as a reported percentage, but it should not be interpreted as a precise population rate.

What does the sample-size illustration mean?

The planning illustration is not the trial’s own design justification and is not observed power. It uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it describes an effect to detect as a stated fraction of the observed effect. The registry record does not report the underlying protocol justification or establish that the trial used these assumptions to plan enrollment. Such illustrations are hypothetical planning aids: they describe sample sizes under stated assumptions, not the probability that this completed study detected an effect.

The record does not report a statistical analysis plan, whether interim analyses were planned or performed, or how missing observations were handled. It reports no outcome analyses. In general, these details matter because model choice, analysis population, repeated-event handling, follow-up duration, and missingness can change estimates and their uncertainty. Without those details and the underlying results, the posted safety summaries should be read descriptively rather than as a complete inferential analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures but reports no analyses. It does not report the full set of outcome results, the numerical primary endpoint result, or a statistical analysis plan. The second measure is not described in the available record details. As a result, it is not possible to determine which outcomes were formally tested, whether any outcomes were prioritized after data collection, or whether adjustments for multiple testing were planned.

Multiplicity arises when several outcomes, time points, subgroups, or comparisons are tested. General statistical context: conducting many tests can increase the chance of at least one apparently notable result under a null model. Methods to address that issue depend on the planned analyses and the questions of interest. No multiplicity procedure is reported in the registry record, so none can be assumed.

The record defines a Safety Analysis Set, but does not report how missing outcome observations were handled or whether all participants contributed through the Month 24 visit. It does not state whether event data were incomplete, whether follow-up differed across participants, or whether any imputation or sensitivity analysis was conducted. Missing data can affect both the apparent event burden and the precision of estimates, particularly when the reason for missingness is related to health status or treatment experience. These are general concerns, not claims that missing data occurred in this study.

Because allocation was non-randomized and the safety summary lists no participants at risk in Cohort 2, the information does not support a balanced between-cohort estimate. The lack of posted analyses also means that no adjusted comparison or efficacy conclusion can be evaluated.

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: cellulitis (5.3%), right middle lobe pneumonia (5.3%).

The registry’s adverse-event summary reports Cohort 1 with 19 participants at risk, 2 affected by serious events, 18 affected by other events, and zero deaths. It lists cellulitis and right middle lobe pneumonia as the leading serious-event terms, each reported at 5.3%. Cohort 2 is listed with zero participants at risk and zero affected by serious events, other events, or deaths.

These summaries should be read as descriptive registry entries. The affected-participant figures are not the same as the primary endpoint’s total number of events: one participant may have experienced more than one event. The record does not provide the primary event-count result, details of event recurrence, or uncertainty estimates for the affected counts and term percentages.

The Cohort 2 zeros do not indicate that no events occurred among a populated group; the summary lists zero participants at risk in that cohort. The record does not explain the reason. Because the trial was non-randomized and the cohorts were not a like-for-like control comparison, their summaries cannot establish a comparative safety effect. The registry also does not report enough detail to assess event relatedness, severity beyond the serious classification, or completeness of event capture.

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

The registry record establishes that a prospective, multicenter, open-label, first-in-human Phase 1/2 study evaluated VC-01™ Combination Product in subjects with Type 1 Diabetes Mellitus. It describes two sequential cohorts with different implant counts and defines a safety population based on enrollment and attempted implant surgery. The primary safety outcome was the number of adverse events reported through the Month 24 visit.

The posted safety summary provides selected descriptive information: Cohort 1 has 19 listed at risk, 2 affected by serious events, 18 affected by other events, and zero deaths. Cellulitis and right middle lobe pneumonia are each listed at 5.3% among the leading serious-event terms. The Cohort 2 summary lists zero at risk. Those observations can describe what the registry reports, but they do not provide a controlled estimate of the effect of VC-01 on safety.

The record does not report the primary endpoint’s total event count or an uncertainty estimate. It does not report efficacy analyses, despite efficacy being part of the stated study purpose. The absence of posted efficacy results is not evidence that the intervention had no effect; it means the registry information does not allow that question to be answered.

The study status is listed as terminated, but the reason for termination is not reported in the registry record. The listed dates and enrollment do not establish why the study ended, whether all planned follow-up occurred, or whether results were withheld or unavailable. Interpretation should remain within the boundaries of the posted design and outcome information. No conclusion about clinical benefit, comparative safety, or safety beyond the observed registry summaries follows from these data alone.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the limits of early, non-randomized safety evidence. A first-in-human study can describe observed events and the practical experience of an intervention, but its design does not automatically support a causal comparison. Here, the open-label, sequential, non-randomized structure means that the cohorts are not randomized counterparts. That distinction is central when reading any apparent difference across groups.

The endpoint also illustrates why outcome definitions matter. The primary measure is the number of adverse events, whereas the registry’s posted safety summaries describe affected participants and serious-event terms. Event counts and affected-participant counts are related but not interchangeable. Without the primary count result, the registry’s separate safety summaries cannot substitute for that endpoint.

The record’s safety-population rule is explicit about attempted implant surgery, including whether or not units were implanted. Clear population definitions are important for interpreting denominators and the scope of a safety estimate. At the same time, a definition cannot resolve unanswered questions about exposure, follow-up completion, event recurrence, or missingness when those details are not reported.

Finally, the registry states an efficacy aim but reports no outcome analyses. That gap separates the scientific question the study intended to address from the evidence available for evaluation. It underscores why conclusions should follow posted estimates and their precision, rather than trial objectives alone. This record supports a careful description of design and selected adverse-event information, but not a complete assessment of efficacy or comparative effects.

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 trial-specific limitation is the non-randomized, open-label, sequential design. The cohorts are not a like-for-like control comparison, and the registry does not provide a concurrent randomized control group. Differences in participant selection, timing, exposure, or event observation could affect descriptive comparisons.

The cohort-specific safety summary is also uneven: it lists 19 participants at risk in Cohort 1 and zero at risk in Cohort 2. The registry does not explain why Cohort 2 has no participants listed in that summary. Its zero adverse-event and death entries therefore cannot be interpreted as event-free experience for an enrolled cohort.

The primary endpoint is identified, but its numerical result is not reported in the registry record. The record also does not report an uncertainty interval, participant-level event history, event recurrence, or detailed event attribution. It does not state whether all participants were followed through the Month 24 visit or how incomplete follow-up was handled. These omissions prevent a fuller assessment of event burden and precision.

Although the study purpose included efficacy, efficacy results and analyses are not reported. The registry lists two outcome measures but does not provide detailed information on the second measure in the available record. The statistical analysis plan, sample-size justification, interim-analysis procedures, and multiplicity handling are also not reported in the registry record.

The record lists a terminated status without giving the reason. Consequently, the status alone cannot establish whether termination related to safety, feasibility, enrollment, administrative decisions, or another cause. These limitations constrain interpretation; they do not establish that an unreported event or analysis occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Safety, Tolerability, and Efficacy Study of VC-01™ Combination Product in Subjects With Type I Diabetes Mellitus — NCT02239354.
• Registry record last updated 2022-03-24; status last verified 2022-02.
• Results first posted 2022-03-24.
• 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

NCT02239354 is a prospective, multicenter, open-label, first-in-human Phase 1/2 study of VC-01™ Combination Product in subjects with Type 1 Diabetes Mellitus. It used non-randomized, sequential cohorts: Cohort 1 was assigned 2 implants and Cohort 2 was assigned 4 or 6 implants. Enrollment was 19, the sponsor was ViaCyte, and the registry lists the study status as terminated.

The primary endpoint was the number of adverse events reported through the Month 24 visit. The registry describes a Safety Analysis Set based on enrolled subjects in whom implant surgery was attempted, whether or not units were implanted. The posted safety summary lists serious and other affected-participant information for Cohort 1, but the numerical primary event-count result and efficacy analyses are not reported in the registry record. The reason for termination and the handling of missing observations are also not reported.