AllogeneiC Human Mesenchymal Stem Cells (hMSC) in Patients With Aging FRAilTy Via IntravenoUS Delivery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AllogeneiC Human Mesenchymal Stem Cells (hMSC) in Patients With Aging FRAilTy Via IntravenoUS Delivery (NCT02065245), a randomized phase 1, phase 2 study. The primary outcome is Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs).

2. Clinical Question

The central question is about short-term safety after infusion, rather than a single measure of improvement in frailty. The primary endpoint counts serious events within the stated period; the registry record does not provide a single comparative treatment-effect estimate or statistical test for that endpoint.

The record also identifies secondary measures related to frailty, mobility, weight, hand grip strength, exhaustion, and quality of life. These measures describe additional areas of interest, but their outcome results and analyses are not reported in the registry record. Consequently, the posted information supports a description of the registered study question and reported safety counts, not a conclusion about comparative changes in frailty or function.

3. Trial Design

The registry describes NCT02065245 as a Phase I/II, randomized, double-blind, placebo-controlled, parallel-group trial. It lists an enrollment of 65 participants, the condition frailty, and Longeveron Inc. as the sponsor. The study started on 2014-03-03, reached primary completion on 2019-10-02, and has completed status in the record.

The study included pilot-phase groups receiving different cell doses, randomized-phase groups receiving cell doses or placebo, and an Addendum B antibiotic-free cell group. The listed cell doses include 20 million allo-hMSCs/kg, 100 million allo-hMSCs/kg, and 200 million allo-hMSCs/kg. The randomized phase included two cell groups and a placebo group. These groups are not interchangeable for interpretation: they belong to different phases or addenda, and the registry record does not report a single analysis comparing all groups.

Some group descriptions allow additional infusions, and the primary endpoint population description says participants could opt in to additional infusion based on cohort. For the randomized placebo group, the description also allows one additional cell infusion. These options mean the listed groups can involve differing exposure plans. The record does not report how many participants opted in, whether additional infusions occurred for each participant, or how such exposure was incorporated into outcome analyses.

The record names several interventions and describes intravenous administration. It does not report the detailed allocation sequence, the procedures used to maintain masking, or a protocol-level explanation of how the pilot and randomized phases related to one another. Those details should not be inferred from the broad design labels.

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.

Only the first 6 of 7 groups are shown.

Infusion 1

Reasons for not completing this period:

Infusion 2

Reasons for not completing this period:

Infusion 3

Reasons for not completing this period:

Infusion 4

Analysis population for the primary outcome, as defined in the registry: Participants were allowed to opt-in to receive additional infusion based on cohort

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.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs), measured over One Month post infusion.

The primary endpoint is the incidence of any treatment-emergent serious adverse events, measured as incidents one month post infusion. The registry defines the composite to include death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically significant laboratory test abnormalities. The listed laboratory measures include serum chemistry and hematology results.

A serious-event endpoint is used to capture important safety outcomes rather than focusing only on a single symptom or laboratory value. Combining several event types can make a broad safety assessment possible, but the composite can include events with different clinical meanings and different causes. A count of composite events does not, by itself, show which component drove the count or whether an event was related to treatment.

The registry record does not report the specific thresholds used to classify laboratory abnormalities as clinically significant, nor does it provide event-level detail or a statistical comparison for the endpoint. It also describes participants as able to opt in to additional infusion based on cohort. The reported time frame is one month post infusion, but the record does not explain how follow-up timing was handled for participants receiving additional infusions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry labels the study randomized, double-blind, and parallel-group. These terms describe aspects of the intended design: random allocation is meant to reduce systematic differences between groups, masking is intended to limit the influence of expectations, and a parallel-group design assigns participants to a group for comparison. The record does not report the randomization procedure or masking details, so the exact safeguards cannot be assessed from the registry description alone.

What does a count endpoint show?

The primary outcome is reported as a number of treatment-emergent serious adverse events, with participants at risk and participants affected listed by group. A count is directly interpretable as a description of what was recorded in those groups. It is not automatically a treatment-effect estimate. A comparative estimate would require a defined contrast, an analysis method, and a measure of uncertainty. Those comparative analyses are not reported in the registry record.

In general, a confidence interval expresses the range of values reasonably compatible with the data under the assumptions of an analysis. It can show how uncertain an estimate is, which matters especially when groups are small or events are uncommon. No confidence intervals for the primary endpoint are reported in the registry record, so the precision of a treatment-group contrast cannot be evaluated from the posted counts alone.

Why does the composite definition matter?

A composite outcome combines several event types into one endpoint. This can make it easier to monitor a broad set of safety concerns, but an overall count can conceal which components occurred. Components can also differ in severity, frequency, and clinical interpretation. The registry lists the components of its serious-event definition, but it does not report a component-by-component breakdown that connects each event to its group and classification. Laboratory abnormalities are included when clinically significant, but the criteria for that classification are not reported in the registry record.

How should the groups be compared?

There are pilot groups, randomized-phase groups, and an antibiotic-free cell group. Their group sizes and treatment descriptions differ, and the record describes options for additional infusions in some cohorts. A comparison across all groups would need to account for which phase a participant entered, the assigned treatment and dose, and actual exposure to further infusions. The registry record does not report a single analysis combining these groups, or an analysis plan specifying which comparisons were intended. The randomized-phase placebo group is a comparator within that phase, but the posted counts alone do not provide an inferential estimate of the difference between it and either cell group.

General statistical interpretation also depends on the unit of analysis. The endpoint description uses incidents, while the adverse-event listing gives counts of participants affected and at risk. A participant can potentially have more than one incident, so event counts and participant counts are not necessarily equivalent. The record does not report event-level counts or clarify how repeated events were handled. The group-level figures should therefore be interpreted as participant counts in the adverse-event listing, not as a complete account of all event occurrences.

What do planning illustrations mean?

Planning sample-size illustrations are based on assumptions and are not observed trial outcomes. The stated assumptions for the illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. Such illustrations are hypothetical planning aids, not evidence that the trial had a particular power after completion. The record does not report a protocol-based sample-size justification, and the posted information does not identify an original target effect or explain how enrollment was selected.

The registry reports no analyses for the outcomes. As a result, no model, adjustment method, inferential procedure, or analysis population can be described as the trial's reported method. General methods can explain what would be needed for interpretation, but they cannot replace an analysis that is not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary serious adverse event outcome and secondary measures of frailty, mobility, weight, grip strength, exhaustion, and quality of life. When a study evaluates many outcomes or comparisons, the chance of finding at least one apparently unusual result can increase if each is tested separately. Statistical approaches can address this multiplicity, but the choice depends on which outcomes and contrasts were prespecified and how confirmatory the analyses were intended to be.

The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which comparisons were designated as primary for inference. It also reports no analyses for the listed outcomes. Therefore, there is no basis in the record to determine whether multiplicity was controlled or how secondary findings should be prioritized.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not state how many participants completed each assessment, how missing outcome values were handled, or whether the analyses followed intention-to-treat, per-protocol, or another population definition. Those details matter because incomplete follow-up can affect both the estimated outcome and its uncertainty. The option for additional infusions makes exposure and follow-up handling particularly relevant, but the registry record does not explain how either was incorporated into analyses.

These are reporting gaps, not evidence that a particular method was or was not used outside the registry record. Without the analysis plan and outcome analyses, the influence of multiplicity, missing data, and population selection cannot be assessed.

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

Serious events with the highest arm-level rate: upper respiratory infection (20.0%), microscopic hematuria (20.0%), congestive heart failure (10.0%), leukocytosis (10.0%), stroke (5.0%).

The serious adverse event listing reports participants at risk and participants affected for each group. The affected counts are 0 of 5, 1 of 5, and 1 of 5 in the three pilot groups; 0 of 10, 2 of 10, and 0 of 10 in the randomized-phase groups; and 1 of 20 in the antibiotic-free cell group. These counts describe the registry's group-level record. They are not adjusted comparisons and do not establish that a treatment caused an event.

The registry separately lists deaths as 0, 0, 1, 0, 1, 0, and 1 across the groups in their displayed order. Because death is part of the primary composite definition, the separate listing should not be added to the affected counts. The record does not clarify whether the listed deaths overlap with the participants counted as affected, nor does it report event-level details or attribution.

The registry lists serious-event terms with percentages, but does not report their denominator or group distribution. These percentages therefore should not be treated as rates for a specific treatment arm. Small group counts also mean that the absence of a recorded event in a group is not proof that no risk exists.

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

The posted information establishes that the trial enrolled participants with frailty and evaluated intravenous allogeneic human mesenchymal stem cells, including different dose groups and a placebo group in the randomized phase. It also provides group-level serious adverse event counts and separately reported death counts. These are descriptive safety data from the registry record.

The counts do not by themselves identify a causal effect of treatment. The groups differ by phase, dose, and addendum, and some group descriptions allow additional infusions. The record does not provide an adjusted comparison, uncertainty intervals, or enough event-level detail to evaluate whether differences in counts are compatible with chance or reflect treatment-related differences. The listed deaths are not accompanied by narratives or attribution.

The primary endpoint has a specified timeframe of one month post infusion and a composite definition. The registry record does not report how the timeframe was applied when additional infusions occurred, nor does it report criteria for laboratory abnormality severity. These details limit interpretation of exactly what each group-level count represents.

The study also names secondary outcomes relevant to frailty and quality of life, but the results and analyses for those measures are not reported in the registry record. No conclusion about changes in mobility, strength, exhaustion, or quality of life can be drawn from the posted results. Likewise, the record does not report a statistical analysis showing whether cell treatment differed from placebo.

In short, the posted results are a limited descriptive account of serious adverse events. They do not provide a definitive estimate of comparative safety or evidence about efficacy. Interpreting broader trial conclusions would require outcome analyses, uncertainty measures, participant follow-up information, and details of event classification that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registered primary endpoint is a safety composite, while the study also includes several phases, dose groups, and an addendum group. That structure makes clear comparison definitions important. A simple reading across every listed group could mix distinct study components and exposure plans rather than isolate a single randomized contrast.

The group counts also illustrate why descriptive event counts need context. The number of participants at risk varies across groups, and the affected counts are sparse. Without uncertainty estimates or a reported comparison, raw counts cannot show how precisely the groups differ. A zero count is still compatible with nonzero underlying risk, while a small difference in counts does not automatically establish a meaningful treatment effect.

The composite endpoint combines death, serious clinical events, hospitalization, and laboratory abnormalities. Such a broad endpoint can support safety surveillance, but interpretation depends on knowing which components occurred and how events were classified. The registry record does not provide the component-level analysis or detailed event attribution needed for that assessment.

Finally, the trial's outcome list extends beyond safety to frailty, mobility, and quality of life, but those outcome analyses are not reported in the registry record. This distinction is important: a registered outcome is not the same as a posted result, and a planning illustration is not observed evidence. The available record supports careful description of design and safety counts, while leaving comparative inference and secondary outcome interpretation 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 registry record does not report statistical analyses for the outcomes, so no treatment-effect estimates, confidence intervals, or hypothesis tests are available for interpretation. It does not report the protocol-based sample-size justification, the analysis populations, handling of missing data, or a multiplicity plan. These omissions limit evaluation of precision, bias, and the intended priority of outcomes.

The primary endpoint combines multiple kinds of events, but the record does not provide a component-level breakdown or the criteria for clinically significant laboratory abnormalities. The serious-event term percentages have no stated denominator or group assignment in the record, so they cannot be interpreted as arm-specific event rates.

The listed study components include pilot groups, randomized-phase groups, and an antibiotic-free cell group. Some descriptions permit additional infusions, but the registry record does not state how many participants received them or how those exposures were reflected in follow-up and analysis. It also does not provide enough information to establish whether separate death counts overlap with the participants counted for the serious-event endpoint.

The group-level event counts are small and descriptive. Without inferential analyses or uncertainty measures, they do not support a precise comparison among doses or against placebo. Further details about randomization, masking procedures, event adjudication, follow-up completeness, and participant-level outcomes are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: AllogeneiC Human Mesenchymal Stem Cells (hMSC) in Patients With Aging FRAilTy Via IntravenoUS Delivery — NCT02065245.
• Registry record last updated 2021-07-14; status last verified 2021-07.
• Results first posted 2021-04-27.
• 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

NCT02065245 is a completed Phase I/II randomized, double-blind, placebo-controlled, parallel-group trial sponsored by Longeveron Inc. It enrolled 65 participants with frailty and evaluated intravenous allogeneic human mesenchymal stem cells in pilot, randomized, and addendum groups. The primary endpoint was treatment-emergent serious adverse events one month post infusion.

The registry reports group-level counts of participants affected by serious adverse events and separate death counts. It lists secondary outcomes related to frailty, mobility, weight, strength, exhaustion, and quality of life, but their analyses are not reported in the registry record. No inferential outcome analyses, confidence intervals, missing-data methods, or analysis populations are reported.