Efficacy and Safety of AMG0001 in Subjects With Critical Limb Ischemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of AMG0001 in Subjects With Critical Limb Ischemia (NCT02144610), a randomized phase 3 study. The primary outcome is Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI).

2. Clinical Question

The clinical question is whether outcomes recorded after assignment to AMG0001 differ from outcomes after assignment to matching placebo among participants with critical limb ischemia. The record identifies a parallel-group, randomized trial and describes the treatments, but it does not provide detailed eligibility criteria, participant flow, or baseline clinical characteristics. Those omissions limit assessment of how closely the enrolled population corresponds to any particular clinical setting.

The primary outcome description names several kinds of events and multiple follow-up intervals. It does not reduce those elements to a single reported comparison in the available record. The registry therefore frames a broad clinical question, but the information recorded does not establish a result for any individual event, interval, or combined measure.

3. Trial Design

The registry describes a Phase 3, randomized, double-blind, placebo-controlled study with a parallel-group model and quadruple masking. Enrollment is recorded as 46. The sponsor was AnGes USA, Inc. The study started on 2014-11-12, and the primary completion date is recorded as 2016-11-28. Its status is terminated; the reason for termination is not reported in the registry record.

Participants assigned to the AMG0001 arm were scheduled to receive intramuscular HGF plasmid injections in muscles of the affected lower limb. The arm description specifies four sets of injections, with injections two weeks apart, starting at Day 0 and again at Month 3 in the first cycle, then at Month 9 and Month 12 in the second cycle. Participants assigned to placebo were scheduled to receive matching placebo using the same described schedule. The registry record does not report whether all participants completed the planned injections or whether the schedule changed during conduct of the trial.

The primary outcome timeframe is 18 months. The registered description gives frequency tables for intervals from Day 0 to 6 months, Day 0 to 12 months, and Day 0 to 18 months, with Fisher's Exact test identified for treatment comparison. The record lists 12 outcome measures and 79 analyses, but does not explain how those measures and analyses relate to the registered primary question or how they were prioritized.

Randomization and masking are design features intended to reduce bias in treatment assignment and outcome assessment. The record does not describe the randomization sequence, allocation concealment, or which people were masked. It also does not report the analysis populations, participant flow, protocol deviations, or a statistical analysis plan. These details are important for judging how the planned design was implemented and how the reported comparisons should be interpreted.

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: Of the 98 subjects screened, 46 met the entry criteria and were randomized (1:1) into the study to receive AMG0001 or placebo as 4 sets of injections 2 weeks apart at Day 0, Month 3, Month 9, and Month 12.

Overall Study

Reasons for not completing this period:

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 Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI), measured over 18 months.

The primary outcome is described as major amputation or revascularization of the index leg, all-cause death, and incidence of stroke and myocardial infarction. The registry labels its unit as participants and describes frequency tables across intervals from Day 0 to 6 months, Day 0 to 12 months, and Day 0 to 18 months. It identifies Fisher's Exact test for treatment comparison. The registry record does not provide the frequencies, comparison estimates, or test results for this outcome.

These events represent different kinds of clinical outcomes. Amputation and revascularization concern the affected leg; death is an outcome regardless of cause; stroke and myocardial infarction are additional events. Measuring such events can describe important clinical consequences over follow-up, while intervals can show how event frequencies accumulate or vary over time. That is a general explanation of why an endpoint may include event counts and follow-up periods, not evidence that any particular result occurred in this trial.

The description names several event categories and several time intervals, but the registry record does not clarify whether the categories were analyzed as a combined endpoint, as separate outcomes, or in another arrangement. It also does not report a participant-level rule for handling multiple events. Accordingly, the registered wording should not be read as a single interpretable treatment effect without the actual outcome definitions and results. Those details, including whether the listed outcomes are mutually exclusive and how repeated events were counted, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a specific statistical test for the primary treatment comparison: Fisher's Exact test. It also describes the outcome as participant counts and gives multiple follow-up intervals. The record does not report the test results, the underlying primary outcome counts, or an effect estimate. The following explains the named method in general and distinguishes it from information that is not documented for this trial.

What does Fisher's Exact test assess?

Fisher's Exact test is a method for comparing categorical outcomes between groups. A categorical outcome places observations into categories, such as whether a participant experienced an event or did not experience an event during a defined period. The test evaluates how compatible the observed pattern of counts is with a hypothesis of no association between group assignment and outcome category. It is called exact because its calculation uses the possible arrangements of the observed counts under that hypothesis, rather than relying on a large-sample approximation.

In general, the test can be useful when counts are limited, because it does not depend on the same large-sample approximation used by some other categorical-data tests. That general property does not establish whether its assumptions or implementation were appropriate in this particular trial. The record does not report the exact data arrangement used for each comparison, whether observations were treated as independent for each interval, or whether other methods were used for analyses beyond the stated treatment comparison.

A test result alone would not describe the magnitude of a treatment difference. A p-value, if reported, would address how compatible the observed data are with a specified null hypothesis under the test assumptions; it would not be the probability that the null hypothesis is true. The registry record does not give a primary-outcome p-value. Nor does it give a confidence interval or another measure of the range of effect sizes compatible with the data. In general, a confidence interval conveys statistical uncertainty around an estimate, but no such primary-outcome interval is reported.

How should counts and intervals be understood?

For a binary outcome, a participant is generally classified according to whether the defined event occurred within the relevant observation period. The record describes the primary outcome unit as participants and lists intervals from Day 0 to 6 months, Day 0 to 12 months, and Day 0 to 18 months. It does not report the counts for these intervals or clarify whether the intervals are cumulative, mutually exclusive, or analyzed in another way. That distinction matters: cumulative intervals can include participants whose events were already counted in an earlier interval, whereas separate intervals can represent different periods of follow-up.

The registered outcome also names several event types. Combining event types can create a composite outcome, while analyzing each event separately yields several comparisons. Those approaches answer different questions. A composite result can be influenced by the more frequent or differently consequential components; separate results can raise the number of statistical comparisons. The record does not specify whether the named events were combined, analyzed separately, or reported using both approaches. It therefore does not support attributing a single treatment effect to a specific interpretation of the endpoint.

In general, repeated events and overlapping event categories require clear rules. A participant might experience more than one type of event or more than one event over follow-up. Whether the analysis counts participants with any event, counts all events, or uses time to first event changes the estimand and the statistical method. The primary outcome description uses participant counts, but the registry record does not state how multiple events within a participant were handled. It also does not report a time-to-event analysis for the primary outcome.

What do the planning assumptions mean?

The registry record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustration considers an effect to detect stated as a fraction of the observed effect. Such an illustration asks how a hypothetical future study might be planned under chosen assumptions; it does not describe a randomized comparison in the current trial.

In general, a sample-size calculation depends on assumptions about the effect to detect, variability or event frequency, allocation, and the chosen statistical error rate. Changing those assumptions changes the resulting planning requirement. The record characterizes these calculations as planning illustrations, not as the trial's own design justification. Their results are not reported in the registry record. They must not be interpreted as observed power, which is not a useful substitute for an effect estimate and uncertainty interval after a study has been conducted.

What remains undocumented?

The record does not report whether treatment effects were adjusted for covariates, how missing outcome data were handled, what analysis population was used, or whether the analysis followed randomized assignment. It does not report a prespecified hierarchy for the 12 outcome measures or the 79 analyses, or whether multiplicity adjustments were applied. It also does not provide the primary outcome estimates or their uncertainty. These are not minor presentation details: they affect what population and question an analysis represents, how robust a comparison is to incomplete follow-up, and how the chance of misleading findings is managed across multiple analyses.

Thus, the documented method is limited to the named Fisher's Exact test for treatment comparison and the stated frequency-table approach. General properties of that test can explain how categorical comparisons are made, but they cannot fill in unreported design choices or results. Interpretation should remain anchored to the actual outcomes and analysis details recorded in the registry.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures and 79 analyses. That indicates a broad set of recorded outcome and analysis entries, but the record does not explain their relationship, identify a complete hierarchy, or state which comparisons were primary, secondary, or exploratory beyond the named primary outcome. It also does not report whether any multiplicity adjustment was planned or applied. When many outcomes or comparisons are examined, the chance of obtaining apparently notable results by chance can increase; methods such as prespecification, hierarchy, or adjustment can help address that issue in general. No particular approach can be attributed to this trial from the registry information.

Missing-data methods are not reported in the registry record. The record does not explain how participants with incomplete follow-up, unavailable outcome measurements, or withdrawal were handled. It also does not report whether missingness was summarized by treatment group or whether sensitivity analyses assessed alternative assumptions. These details matter because an analysis based only on observed outcomes may represent a different set of participants than the randomized groups, and conclusions can depend on why data are missing.

The analysis population is also not reported. The record does not say whether the primary comparison used all randomized participants, participants who received treatment, participants with available outcome data, or another defined population. Randomization supports fair group comparisons when analysis and follow-up preserve the assigned groups, but the registry information does not establish how that principle was implemented.

Termination is recorded as the study status, but the reason and its implications for follow-up, missingness, and planned analyses are not reported. These omissions prevent assessment of whether the number or timing of analyses changed during the study. They also make it impossible to assess how multiplicity and incomplete data may have affected any primary outcome findings, which themselves are not reported in 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: acute myocardial infarction (8.7%), suicidal ideation (4.3%), pneumonia (4.3%), respiratory failure (4.3%), angina unstable (4.3%).

The registry records serious adverse events for the AMG0001 group as 7 participants affected among 23 at risk, and for the placebo group as 9 among 23 at risk. Other adverse events are recorded as 5 participants affected among 23 at risk in the AMG0001 group and 7 among 23 at risk in the placebo group. Deaths are recorded as 3 in the AMG0001 group and 2 in the placebo group. These are descriptive counts from the registry record; they do not establish that treatment caused or prevented any event.

The record lists acute myocardial infarction at 8.7%, and suicidal ideation, pneumonia, respiratory failure, angina unstable, and multiple organ dysfunction syndrome at 4.3% each among the top serious adverse event terms. The registry information does not clarify the denominator or treatment-group distribution for each listed percentage. The percentages should therefore be read as reported terms, not as group-specific risks.

Adverse-event counts do not by themselves show event severity beyond the serious-event classification, timing, duration, recurrence, or relationship to treatment. The registry record does not provide those details or uncertainty intervals for safety comparisons. Differences in raw counts should not be treated as causal effects, particularly without information on follow-up completeness, event ascertainment, or analysis methods.

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

The registry record establishes that a randomized, placebo-controlled Phase 3 study of AMG0001 in critical limb ischemia was conducted and later marked terminated. It describes the injection schedule, the primary outcome categories and follow-up intervals, and selected adverse-event counts. These registry entries help define the design and the questions the study was intended to address.

The record does not report the primary outcome frequencies or treatment-comparison results. It therefore does not show whether AMG0001 and placebo differed in major amputation or revascularization of the index leg, all-cause death, stroke, or myocardial infarction. The absence of those results is not evidence of no effect, and it is not evidence of an effect. The size, direction, and precision of a primary treatment comparison cannot be determined from the information recorded.

The safety information is also limited. Counts for serious adverse events, other adverse events, and deaths are recorded by treatment group, and selected serious-event terms are listed with percentages. These summaries do not establish causation, comparative risk, or the clinical importance of any difference. The record does not report the details needed to assess event timing, treatment relatedness, or uncertainty in the group comparisons.

More broadly, the record does not report why the study was terminated, the analysis populations, missing-data handling, or multiplicity procedures. Those details would help readers understand how closely the analyses followed the randomized design and how much confidence to place in any reported comparisons. The trial's recorded design and safety counts can be described, but efficacy interpretation requires primary outcome results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registered primary outcome spans different clinical event types and multiple follow-up intervals. A major amputation, revascularization, death, stroke, and myocardial infarction are not interchangeable events. How they are combined, counted, and timed determines the question answered by a treatment comparison. The registry record does not clarify the analysis structure for these components, which makes the endpoint definition central to interpretation.

The study is recorded as randomized, placebo-controlled, and quadruple-masked, features designed in general to limit bias in group assignment and assessment. Yet a design label does not replace reporting of the randomization procedure, masking roles, participant flow, and analysis population. Those details matter when deciding whether observed comparisons preserve the protections intended by randomization. The record does not report these implementation details.

The registry lists 12 outcome measures and 79 analyses. A large set of outcomes and analyses raises questions about which comparisons were prespecified and how the risk of chance findings was managed. The record does not report a hierarchy or multiplicity strategy. This is particularly relevant when the primary outcome itself includes several event categories and intervals.

The status is terminated, but the reason is not reported. Without that context, readers cannot assess whether termination affected follow-up, data completeness, or planned analyses. Further, the primary outcome results are not reported, so this record cannot support an efficacy conclusion. These statistical limitations do not erase the design information; they define what the registry can and cannot establish.

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 provides limited detail for assessing the primary outcome. It names several event categories and multiple time intervals but does not report outcome frequencies, comparison results, estimates, or uncertainty intervals. It also does not explain whether the events were analyzed as a composite, separately, or by another approach. The handling of participants with multiple event types or repeated events is not reported.

The record does not report detailed eligibility criteria or baseline characteristics. Without them, readers cannot assess the clinical profile of enrolled participants or how well the study population reflects a particular care setting. Participant flow, treatment adherence, and the extent of follow-up are also not reported. The scheduled injection regimen is described, but actual receipt and completion are not.

The registry status is terminated, but the reason is not reported in the registry record. It is therefore not possible to assess whether termination affected the planned follow-up, data completeness, or statistical analyses. The analysis population and approach to missing data are not reported, nor is there information about whether the primary analysis followed randomized assignment.

Although Fisher's Exact test is named for treatment comparison, the record does not give the primary test result or explain other analysis choices. It does not report a statistical analysis plan, multiplicity procedures, or the relationship among the 12 outcome measures and 79 analyses. The reported safety counts also lack detailed timing, event-level context, and uncertainty measures. These gaps constrain interpretation of both efficacy and safety without establishing that the study's underlying data or analyses were necessarily inadequate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of AMG0001 in Subjects With Critical Limb Ischemia — NCT02144610.
• Registry record last updated 2019-08-13; status last verified 2019-07.
• Results first posted 2019-08-13.
• 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 randomized, parallel-group, quadruple-masked, placebo-controlled Phase 3 study of AMG0001 in people with critical limb ischemia. Enrollment is recorded as 46, the sponsor is AnGes USA, Inc., and the study status is terminated. The reason for termination is not reported in the registry record.

The primary outcome concerns major amputation or revascularization of the index leg, all-cause death, stroke, and myocardial infarction, assessed over intervals through 18 months. Fisher's Exact test is identified for treatment comparison, but primary outcome counts and results are not reported. The record lists serious and other adverse-event counts and deaths by treatment group, along with selected serious-event terms. Analysis populations, missing-data methods, multiplicity procedures, and detailed participant flow are not reported.