A Study to Evaluate Safety, Engraftment, and Efficacy of VC-01 in Subjects With T1 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Safety, Engraftment, and Efficacy of VC-01 in Subjects With T1 Diabetes Mellitus (NCT04678557), a non-randomized phase 1, phase 2 study. The primary outcome is Cohort 1: The Percentage of Graft Cells Present at Post-implant Time Points Relative to Pre-clinical Models.

2. Clinical Question

The clinical question is about safety, engraftment and efficacy, as stated in the study title. The primary endpoint described in the registry addresses graft-cell viability and its comparison with animal-model expectations. It is not a direct measure of a functional cure, and the registry record does not report clinical efficacy results in the registry record for this analysis. Because the study was open-label and non-randomized, its structure does not support a like-for-like causal comparison between treatment and a randomized control group. The animal-model comparison supplies a reference for the viability endpoint, but it is not a concurrent clinical control.

3. Trial Design

NCT04678557 is an open-label Phase 1/2 study of the VC-01 Combination Product in subjects with Type 1 diabetes. Allocation was non-randomized, masking was absent, and the model was sequential. The sponsor was ViaCyte. The registry lists enrollment of 31 and a status of terminated. The recorded study start was 2019-06-25, and primary completion was 2021-11-12.

The study describes two cohorts. Cohort 1 consisted of sentinel units, with up to ten VC-01 sentinels planned. Cohort 2 consisted of dose-finding units, with up to twelve units implanted; up to nine were VC-01 dose-finding implants and the remainder were VC-01 sentinels. These are cohort descriptions, not evidence that every planned unit was implanted. The registry record does not report the exact number of units implanted in each cohort.

The primary endpoint concerns Cohort 1. Sentinel units were explanted and processed for histology, with staining used to identify graft-cell nuclei as a marker of cell viability. The recorded timepoints were Weeks 4, 8, 12 and 26. The endpoint compared the percentage of viable graft cells in explants with the percentage expected from pre-clinical animal models.

Sequential cohorts can allow later study activity to follow earlier activity, but the registry record does not report the protocol’s decision rules or explain how cohort progression was determined. It also does not report the rationale for the sample size, details of interim analyses, or a complete statistical analysis plan. With no random allocation or masking, findings should be read as descriptive study observations rather than as randomized comparative evidence.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: For each timepoint, explanted sentinel units containing PEC-01 cells from the 17 subjects were stained and evaluated for graft cell survival (i.e., viability). Not all subjects had units explanted at every timepoint, and units explanted that had "de minimus" graft cell survival (i.e., minimal, \< 500 cells, \< 4% of pre-clinical controls) could not be evaluated and were not included in the summary table.

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 Cohort 1: The Percentage of Graft Cells Present at Post-implant Time Points Relative to Pre-clinical Models, measured over Weeks 4, 8, 12 and 26.

The primary endpoint is the percentage of viable graft cells in Cohort 1 sentinel units relative to the percentage expected from pre-clinical animal models. Histology was used to stain explanted units and identify graft-cell nuclei; the registry describes these nuclei as indicating that cells were viable. The endpoint is expressed as a mean with standard deviation, and the recorded assessment times are Weeks 4, 8, 12 and 26.

This measure was used to assess potential functional engraftment: whether graft cells remained present and viable after implantation. Comparing the observed viability in human explants with animal-model expectations gives a reference for interpreting the tissue findings. It does not establish that the graft performed a clinical function, nor does it directly measure a clinical benefit. The registry record describes the animal models as based on animal studies performed at ViaCyte, with an internal study report cited.

The endpoint description includes an example stating that at Week 4 the average was 18.27% of viable graft cells compared with what was expected from animal models. That sentence is presented as an example in the outcome description; the registry entries do not include the full outcome data by timepoint, sample sizes at each timepoint, or uncertainty estimates. The population description also notes that not all subjects had units explanted at every timepoint and that units with minimal graft-cell survival were treated specially, but the record text ends before the stated threshold is complete.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure summarized as a mean and standard deviation. In general, a mean describes the central level of a measurement across observations, while a standard deviation describes how spread out those observations are around the mean. Both depend on which units and subjects are included. The registry describes histological measurements of viable graft cells in explanted sentinel units and a comparison with expected viability from pre-clinical models.

What does the animal-model reference mean?

In general, a reference value gives context for interpreting an observed measurement. Here, the endpoint compares the percentage of viable graft cells in participant explants with the percentage expected from animal models. It is not a treatment-control contrast produced by random allocation. It should therefore be read as a comparison between observed human tissue findings and a pre-clinical expectation, not as an estimate of what would have happened to the same participants without the intervention.

The registry’s outcome description names Weeks 4, 8, 12 and 26. In general, repeated timepoints can help describe how a measure varies over follow-up, but each timepoint’s estimate depends on the observations available at that time. The record says that not all subjects had units explanted at every timepoint. Consequently, the number of observations and the composition of the assessed group may differ over time. The registry record does not report the timepoint-specific sample sizes or a method for handling this incomplete set of assessments.

Why does the analysis population matter?

In general, an analysis population defines which participants or measurements contribute to a result. This is especially important for an endpoint based on explanted tissue: the available measurement is tied to a unit being explanted and evaluated. The record says the primary endpoint population involved sentinel units containing PEC-01 cells from 17 subjects, while also noting that not all subjects had units explanted at every timepoint. It further notes that units with “de minimus” graft-cell survival were handled specially. The threshold statement is truncated after “< 50”, so its complete definition and application are not reported in the registry record. These details affect how a mean would be interpreted, because exclusion or non-availability can change the set of observations summarized.

In general, a confidence interval describes the uncertainty around an estimate under the assumptions of the statistical method used. The registry entries do not report confidence intervals for the primary endpoint, so its inferential precision cannot be described. A standard deviation, if reported, would describe variability among observations rather than uncertainty in the estimated mean. Those two quantities answer different questions.

How should sample-size illustrations be read?

The planning illustrations are based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Their effect to detect is stated as a fraction of the observed effect. These are planning illustrations, not the trial’s own design rationale and not observed power. The record does not report the trial’s sample-size justification. The assumptions also describe a two-arm comparison, whereas this study is non-randomized and its cohorts are not like-for-like control arms. Such illustrations therefore do not turn the actual study into a randomized comparison, nor do they establish the precision or power of the trial as conducted.

In general, power is a design concept: it concerns the chance that a specified analysis will detect an effect of a specified size under stated assumptions. It is not a measure of whether a result is true, and calculating power after observing results does not resolve uncertainty in those results. The stated planning approach uses an observed effect as its anchor, so its output should be understood as an illustration of planning requirements under those assumptions, not as an independent validation of the trial findings.

What can be said about hypothesis tests?

The registry entries available for this analysis report zero analyses. No primary-endpoint p-value, confidence interval, or formal comparison result is reported. The registry record does not report the statistical test, model, covariate adjustment, handling of multiple observations from a subject, or rules for missing measurements. Without those details and the underlying results, no inferential claim can be reconstructed. General statistical interpretation should distinguish descriptive summaries from formal estimates and tests; the registry entries support the former only to a limited extent.

General methods for continuous outcomes often rely on assumptions about measurement distributions and independence. Repeated or clustered tissue measurements can violate independence if multiple units come from the same subject. The registry record does not specify whether there were multiple measurements per subject or how any such dependence was handled. General concern about over-dispersion arises when observed variability exceeds what a model assumes; that can make standard errors too small if not accounted for. There is not enough information in the registry record to determine whether over-dispersion was present or relevant to the primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is described at four timepoints: Weeks 4, 8, 12 and 26. Considering multiple timepoints raises a general multiplicity issue: if separate statistical tests are made at several times, the chance of at least one apparently notable result can increase unless the analysis plan accounts for that. The registry record does not report whether formal tests were performed, whether one timepoint was designated as the main inferential focus, or whether any multiplicity adjustment was planned. The registry entries report zero analyses, so there are no posted p-values to interpret across those timepoints.

Missingness also matters. The registry states that not all subjects had units explanted at every timepoint. It does not report the number assessed at each time, the reasons units were unavailable, or a statistical method for handling missing assessments. In general, missing observations can affect a summary if the participants or units with observed measurements differ systematically from those without measurements. The record does not provide enough information to assess whether that occurred.

The outcome description also says that units with “de minimus” graft-cell survival were treated specially, and its text begins a threshold as “< 50” before ending. The complete threshold, whether it refers to a percentage or another quantity, and how these units were handled in the analysis are not reported in the registry record. This prevents a full assessment of the endpoint population and the influence of exclusions or special handling.

The analysis population is only partly described: the endpoint refers to sentinel units from 17 subjects, but timepoint-specific inclusion is unclear. The registry record does not report a complete analysis plan, an imputation approach, or sensitivity analyses. Thus, the effects of missing units, any exclusions, and repeated assessments cannot be evaluated from the registry entries.

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: small intestinal obstruction (7.1%), hypoglycemia (7.1%), subarachnoid hemorrhage (7.1%), vanishing twin syndrome (5.9%).

The registry lists serious adverse events separately from other adverse events for each cohort. In Sentinel Units (Aka Cohort 1), 1 of 17 subjects is listed as having a serious adverse event, and 17 of 17 as having other adverse events; deaths are listed as 0. In Dose-finding Units (Aka Cohort 2), 3 of 14 subjects are listed as having a serious adverse event, and 14 of 14 as having other adverse events; deaths are listed as 0.

The listed serious-event terms include Small Intestinal Obstruction at 7.1%, Hypoglycemia at 7.1%, Subarachnoid hemorrhage at 7.1%, and Vanishing Twin Syndrome at 5.9%. The registry entries available do not specify the event counts, denominators, time period, or whether these terms are reported across the study or within particular groups. The percentages should therefore be read as registry-listed values, not recalculated rates or evidence of a causal relationship.

In general, an adverse event is an event recorded during a study and does not by itself establish that the intervention caused it. A serious adverse event is a distinct reporting category; the registry record’s counts do not provide event-level detail about severity, timing, outcome, or investigator attribution. The cohort figures are descriptive and should not be compared as if participants had been randomized between groups.

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

The results described in the registry concern graft-cell viability in explanted tissue and adverse-event reporting. The Week 4 endpoint description gives an example of 18.27% viable graft cells relative to what was expected from animal models. This example does not provide the complete outcome profile across the recorded timepoints. The registry entries do not report all timepoint estimates, variability, sample sizes, or confidence intervals, so they do not show how precise the endpoint estimates are or how they changed over follow-up.

The endpoint offers information about a biological process: whether graft cells were present and viable in tissue collected after implantation. It does not, by itself, demonstrate functional engraftment in a clinical sense, a functional cure, or a clinical benefit. The registry’s study summary describes VC-01 as intended to provide a functional cure, but that stated intent is not an outcome finding.

The study design also limits interpretation. Participants were not randomized, masking was absent, and the cohorts were sequential rather than like-for-like control groups. The comparison with animal-model expectations is not a concurrent clinical control. Accordingly, the registry entries do not support a causal estimate comparing VC-01 with an untreated or alternative-treatment group.

The safety counts document serious and other adverse events as recorded in the registry, including zero deaths listed in each cohort. Those counts do not establish whether events were related to the intervention and do not supply the detailed context needed to assess individual events. The status is terminated, but the reason for termination and whether it was related to safety, feasibility, or another consideration are not reported in the registry record.

In general, a registry record can describe study intent, design, outcome definitions and selected results without supplying enough information for a definitive efficacy or safety assessment. In this case, the registry entries available support a limited descriptive reading. They do not establish that VC-01 does or does not work, and they do not allow a complete assessment of uncertainty, missing data, or clinical effects.

13. Why This Trial Matters Statistically

This trial raises several important statistical issues in early clinical research. Its main endpoint uses histology to quantify viable graft cells and compares the findings with expectations from pre-clinical animal models. That makes the choice and interpretation of a reference especially important: a biological benchmark can aid description, but it is not equivalent to a concurrent randomized control group.

The endpoint also depends on explanted units being available for evaluation. The registry states that not every subject had units explanted at every timepoint and mentions special handling of units with minimal graft-cell survival. Those features make the analysis population and missing-data rules central to interpretation. Without timepoint-specific counts and complete rules for exclusions, a reader cannot tell how representative the measured units are of all enrolled subjects.

The trial’s sequential, non-randomized structure is another statistical consideration. Cohorts with different roles in a study should not be treated as exchangeable groups merely because both received the same combination product. Randomization and a concurrent control can help distinguish intervention effects from other differences; those features are absent. The record therefore illustrates why descriptive evidence and comparative evidence need to be distinguished.

Finally, a stated objective such as evaluating efficacy does not substitute for reported outcome estimates and uncertainty. The registry entries available include one example in the endpoint description, safety counts, and no reported analyses. A careful statistical reading makes clear which observations are described, which questions remain unanswered, and why a registry endpoint definition alone is not enough to support a treatment-effect conclusion.

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 available endpoint information is incomplete. The registry describes the measure, timepoints and an example at Week 4, but the registry entries available do not include the full outcome summaries at each timepoint, their standard deviations, or confidence intervals. The timepoint-specific numbers of evaluated units are also not reported in the registry record, limiting assessment of precision and changes in the assessed population.

The population description says that not all subjects had units explanted at every timepoint and that units with “de minimus” graft-cell survival received special handling. The threshold text is truncated after “< 50”, and the complete rule and its application are not reported. Reasons for missing explants, the handling of missing measurements, and sensitivity analyses are also not reported in the registry record.

The comparison with animal-model expectations is not a randomized clinical comparison. The study was non-randomized, unmasked and sequential, and the cohort roles differ. No like-for-like control arm is described. The record does not report enough detail to evaluate the animal-model reference, including its variability or how expected values were matched to participant observations.

The safety figures are limited to group-level counts and listed event terms. Event-level timing, duration, severity grading, outcomes and causal attribution are not reported in the registry record. The meaning and denominators for the listed serious-event percentages are also not specified.

The registry lists the study as terminated, but the reason is not reported in the registry record. A complete statistical analysis plan, sample-size rationale, interim-analysis details and explanation of any planned multiplicity handling are likewise not reported. These gaps limit interpretation and do not establish why the study ended or what conclusions its investigators intended to draw.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate Safety, Engraftment, and Efficacy of VC-01 in Subjects With T1 Diabetes Mellitus — NCT04678557.
• Registry record last updated 2023-10-18; status last verified 2023-09.
• Results first posted 2023-10-18.
• 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

NCT04678557 is a terminated, open-label Phase 1/2 study of the VC-01 Combination Product in subjects with Type 1 diabetes. It was non-randomized and sequential, with no masking. The registry lists enrollment of 31, ViaCyte as sponsor, a study start of 2019-06-25 and primary completion on 2021-11-12.

The primary outcome evaluates viable graft cells in Cohort 1 sentinel-unit explants relative to pre-clinical animal-model expectations at Weeks 4, 8, 12 and 26. The description includes a Week 4 example of 18.27%, but the registry entries do not include complete outcome summaries or analyses. The registry lists serious adverse events in 1 of 17 Sentinel Units subjects and 3 of 14 Dose-finding Units subjects, with 0 deaths in each group.

The design and incomplete results support a cautious descriptive interpretation. The registry record does not report a randomized control comparison, complete missing-data methods, a full statistical analysis plan, or the reason for termination.