This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for The Study of an Investigational Drug, Revusiran (ALN-TTRSC), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Patients Whose Disease Has Continued to Worsen Following Liver Transplant (NCT02595983), a na phase 2 study. The primary outcome is Percentage Change From Baseline in Serum TTR at Month 6.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02595983 |
| Phase | Phase 2 |
| Condition | Transthyretin (TTR)-Mediated Amyloidosis, Familial Amyloidotic Polyneuropathy (FAP), ATTR Amyloidosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alnylam Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Adults with transthyretin-mediated amyloidosis whose disease continued to worsen after liver transplantation. The official title specifies familial amyloidotic polyneuropathy with progression after orthotopic liver transplant. The registry record lists 12 enrolled participants.
Intervention
Revusiran, also identified as ALN-TTRSC. The study evaluated its safety and effectiveness. The brief summary says dosing was discontinued and patients were being followed for safety.
Comparator
There was no concurrent control group. The registry describes a single-group study with no allocation and no masking. The study therefore does not provide a randomized, like-for-like comparison against another treatment or a control condition.
Primary question
The primary endpoint was the percentage change from baseline in serum TTR at Month 6. A negative change indicates a reduction in serum TTR. The registry record does not report the Month 6 mean, its standard deviation, or an estimate of the change, so the primary result cannot be quantified from the posted results.
This question concerns a defined group with disease progression after liver transplantation, rather than all people with transthyretin-mediated amyloidosis. The endpoint focuses on serum TTR, a laboratory measure, while the listed secondary outcomes include neurological impairment, quality of life, and disability stage. Those measures address different aspects of disease and should not be treated as interchangeable. The record reports five outcome measures and lists four secondary outcome descriptions. It does not report results for those secondary measures. Consequently, the available registry information identifies what the study set out to assess, but does not establish the observed direction, size, or precision of the primary or secondary outcomes.
3. Trial Design
The registry classifies this as a phase 2, open-label, single-group study. It lists an enrollment of 12 and identifies revusiran as the intervention. Allocation is recorded as not applicable, and masking as none. All patients who received at least one dose of revusiran are described as the study arm. There is no concurrent control arm, so the design cannot directly compare outcomes under revusiran with outcomes under another treatment or under a control condition.
The population of interest was patients with transthyretin-mediated familial amyloidotic polyneuropathy whose disease progressed after orthotopic liver transplant. The study began in 2015-10, had primary completion on 2017-02-06, and is listed as completed. The brief summary states that dosing was discontinued and that patients were being followed for safety. The reason for discontinuation and details of the follow-up schedule are not reported in the registry record.
The primary outcome was percentage change from baseline in serum TTR at Month 6. Secondary outcomes included percentage change in serum TTR over 18 months, change in the modified Neurological Impairment Score composite over 18 months, Norfolk QoL-DN questionnaire score, and the number of participants in each Polyneuropathy Disability stage based on the worst post-baseline score. The record names these outcomes but does not report their results.
Because there is no randomized comparison, a change from baseline would describe participants’ observed course after treatment began; it would not by itself distinguish a treatment effect from other explanations for change over time. The registry record does not report the protocol’s sample-size justification, the detailed statistical plan, or whether interim analyses were planned.
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
| Stage | All Patients |
|---|---|
| STARTED | 12 |
| COMPLETED | 8 |
| NOT COMPLETED | 4 |
Analysis population for the primary outcome, as defined in the registry: Safety analysis set: All participants who received at least a single dose of study drug and for whom data were collected at Month 6.
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.
| Characteristic | Unit | All Patients |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | years | 55.8 (SD 8.65) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 10 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 12 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Familial Amyloidotic Polyneuropathy (FAP) Stage: FAP Stage I: Unimpaired ambulation | Participants | 3 |
| Familial Amyloidotic Polyneuropathy (FAP) Stage: FAP Stage II: Assistance with ambulation required | Participants | 9 |
| Familial Amyloidotic Polyneuropathy (FAP) Stage: FAP Stage III: Wheelchair-bound or bedridden | Participants | 0 |
| Serum Transthyretin (TTR) | micrograms/milliliter (μg/mL) | 192.3 (SD 43.28) |
6. Primary Endpoint
The registry lists the primary outcome as Percentage Change From Baseline in Serum TTR at Month 6, measured over Month 6.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage change from baseline in TTR |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the percentage change from baseline in serum transthyretin (TTR) at Month 6. The registry defines the endpoint as a mean and identifies standard deviation as the measure of dispersion. It also states that a negative percentage change indicates a reduction in serum TTR. The analysis population is described as participants who received at least a single dose of study drug and for whom Month 6 data were collected.
A laboratory measure can provide a defined, quantitative way to assess change over time. A percentage change expresses the change relative to a participant’s own baseline, which can make the result easier to interpret across participants with different starting levels. The mean describes the average change in the analysis population, while the standard deviation describes how much individual observed values vary around that mean. These are general interpretations of the stated statistical measures, not a report of this study’s result.
The registry record does not report the Month 6 mean percentage change or its standard deviation. It also does not report a confidence interval or other estimate of precision for this endpoint. Without those results, the direction and size of the observed average change cannot be established from the posted results, and its variability cannot be described. The endpoint is a serum measure; it should not be read as a direct result for neurological function, quality of life, or disability, which are listed separately as secondary outcomes.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary endpoint and its analysis population, but it does not report the endpoint estimate. In particular, the Month 6 mean percentage change from baseline in serum TTR and its standard deviation are not reported in the registry record. The posted results therefore do not show whether the average change was negative or positive, how large it was, or how variable participant measurements were. Although the endpoint description explains that a negative change indicates a reduction in serum TTR, that definition cannot substitute for the missing result.
There is also no reported confidence interval or other precision estimate for the primary outcome. In general, a confidence interval conveys the range of values compatible with the data under the assumptions of the analysis. Without an estimate and its uncertainty, readers cannot judge how precisely the mean change was estimated. A standard deviation, if reported, would describe variability among observations, but it is not itself a confidence interval for the mean.
The study is listed as open-label and single-group, with no allocation and no masking. Thus, even if a before-and-after change were reported, it would not be a randomized comparison. A baseline-to-follow-up change can describe what happened in the observed group; by itself it cannot establish that revusiran caused the change. Other influences over time, including the course of the condition and differences in who had follow-up measurements, may also matter. The registry record does not report a control group that could help distinguish these possibilities.
The record lists secondary outcomes concerning serum TTR over 18 months, neurological impairment, quality of life, and disability stage, but does not report their results. It also lists no analyses in the registry record. The reason for the discontinuation of dosing is not reported in the registry record; the brief summary only states that dosing was discontinued and patients were followed for safety. These details limit interpretation of the study’s clinical outcomes.
The safety information is separate from the missing efficacy results. The safety population is listed as 12, with 8 affected by serious adverse events, 11 affected in the other adverse-event category, and 2 deaths. The record also lists serious-event terms, each with a reported percentage of 8.3%. Those data describe events recorded in the treated study population; with no concurrent control group, they do not estimate how event frequency compares with an alternative treatment or with no study treatment. Overall, the registry record supports a description of study design and selected safety counts, but not an estimate of the primary treatment effect.
9. Statistical Methods Explained
The registry describes a continuous primary outcome summarized by a mean and standard deviation. The mean is the arithmetic average of the measured percentage changes in the stated analysis population. The standard deviation describes the spread of individual measurements around that average. These measures answer different questions: the mean describes the group’s average observed change, while the standard deviation describes variation among the observations. Neither measure is reported for the primary endpoint in the registry record.
What does percentage change describe?
Percentage change expresses follow-up measurement relative to baseline. It is a way to describe change using each participant’s starting measurement as the reference. The endpoint description specifies that a negative percentage change at Month 6 indicates a reduction in serum TTR. This direction rule clarifies how to read a reported value, but the registry record does not report the value itself. It is therefore not possible to characterize the observed average change as a reduction or an increase.
What would a standard deviation tell a reader?
In general, a standard deviation indicates how dispersed the observed values are around their mean. A smaller spread indicates that measurements are more concentrated around the mean; a wider spread indicates more variation. It is not a measure of the precision of the mean on its own. Precision also depends on how much information contributes to the estimate. The standard deviation for this endpoint is not reported in the registry record, so the variation in Month 6 percentage changes cannot be described.
How does a confidence interval differ?
In general, a confidence interval is an uncertainty interval for an estimated quantity. It helps readers assess the range of values that are reasonably compatible with the observed data and the statistical assumptions. It does not show the spread of individual observations in the same way as a standard deviation. No confidence interval for the primary endpoint is reported in the registry record. Nor does the record provide a p-value or a reported hypothesis test for that endpoint. Without an estimate and an uncertainty measure, neither the size nor the precision of an average change can be assessed.
What does the single-group design allow?
The study is classified as single-group, open-label, with allocation recorded as not applicable and masking recorded as none. In general, a single-group design can describe outcomes observed in a treated population over time. A change from baseline is not, by itself, a comparison with what would have happened without the study intervention. A concurrent control group can support a direct comparison, while random allocation can help make groups comparable on average. This study’s registry record does not describe a concurrent control group or random allocation. Therefore, any within-group change, if reported, would need to be interpreted as an observed course rather than as a controlled estimate of a treatment effect.
What is the role of the analysis population?
The primary endpoint population is defined as participants who received at least a single dose of study drug and for whom Month 6 data were collected. This is a treatment-exposed population with an available-data requirement for the endpoint. In general, results from an available-data population can differ from results that would have been obtained if measurements were available for everyone, particularly if missingness is related to health status or outcome. The registry record does not report the number with Month 6 measurements, the reasons for missing measurements, or a method for handling missing primary endpoint data.
What can be said about planning calculations?
In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, allocation, and statistical method. It is not an observed result, and it is not observed power. The planning assumptions described for the posted sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. The assumptions also distinguish participant-per-arm planning for non-time-to-event outcomes from total-event planning for time-to-event outcomes. These are planning conventions, not features that establish the design or analysis used for this single-group study. The registry record does not report the protocol’s sample-size justification. No calculated planning values or observed primary effect are reported in the registry record, so no planning result can be interpreted from the stated assumptions alone.
10. Multiplicity, Missing Data and Analysis Populations
The record lists five outcome measures, including the primary serum TTR endpoint and secondary outcomes for longer-term serum TTR, neurological impairment, quality of life, and disability stage. It does not report outcome results or a statistical analysis plan describing how multiple outcomes were handled. In general, testing multiple outcomes can increase the chance of a result appearing notable by chance if no multiplicity strategy is used. Whether or how that issue was addressed is not reported in the registry record. The listing of several outcomes alone does not establish that formal hypothesis tests were conducted.
The registry record lists no analyses. It does not report p-values, confidence intervals, or other inferential results for the primary or secondary outcomes. It also does not report whether interim analyses were planned or performed. These details should not be inferred from the outcome list or the study’s phase.
The primary endpoint population includes participants who received at least a single dose and for whom Month 6 data were collected. The record does not report how many participants had those measurements, whether any were missing, why data may have been missing, or what method was used to address missingness. In general, missing-data methods depend on assumptions about why observations are unavailable; different assumptions can affect an estimate. Since neither the amount of missing data nor the handling method is reported, the impact of missing observations cannot be assessed.
The safety population is defined in the adverse-event information, but the record does not give additional detail about endpoint-specific analysis populations or any sensitivity analyses. The registry record also does not report a protocol-based sample-size justification. As a result, the available information does not establish how the study was planned to control error across outcomes, assess missing data, or support the precision of its estimates.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Safety Population | 8 | 12 | 66.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Safety Population | 2 of 12 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Safety Population | 11 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | Safety Population |
|---|---|---|
| Cardiac Arrest | Cardiac disorders | 1 of 12 |
| Cardiac Failure | Cardiac disorders | 1 of 12 |
| Pericardial effusion | Cardiac disorders | 1 of 12 |
| Ascites | Gastrointestinal disorders | 1 of 12 |
| Dysphagia | Gastrointestinal disorders | 1 of 12 |
| Nausea | Gastrointestinal disorders | 1 of 12 |
| Vomiting | Gastrointestinal disorders | 1 of 12 |
| Death | General disorders | 1 of 12 |
| Aspergillus infection | Infections and infestations | 1 of 12 |
| Pyelonephritis acute | Infections and infestations | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Safety Population |
|---|---|---|
| Oedema peripheral | General disorders | 4 of 12 |
| Diarrhoea | Gastrointestinal disorders | 4 of 12 |
| Muscular Weakness | Musculoskeletal and connective tissue disorders | 3 of 12 |
| Nausea | Gastrointestinal disorders | 3 of 12 |
| Renal Failure | Renal and urinary disorders | 3 of 12 |
| Headache | Nervous system disorders | 3 of 12 |
| Nasopharyngitis | Infections and infestations | 3 of 12 |
| Marcocytosis | Blood and lymphatic system disorders | 3 of 12 |
| Vomiting | Gastrointestinal disorders | 2 of 12 |
| Urinary tract infection | Infections and infestations | 2 of 12 |
Serious events with the highest arm-level rate: cardiac arrest (8.3%), cardiac failure (8.3%), pericardial effusion (8.3%), ascites (8.3%), dysphagia (8.3%).
The safety population is listed as 12. The registry reports 8 affected by serious adverse events among 12 at risk, and 11 affected in the other adverse-event category among 12 at risk. It also reports 2 deaths. The record does not provide further detail in these figures about event timing, recurrence, severity beyond the serious-event classification, or the relationship of events to study treatment. These counts should be read as safety observations in the study population, not as comparative estimates.
The serious-event terms listed are Cardiac Arrest, Cardiac Failure, Pericardial effusion, Ascites, Dysphagia, and Nausea. Each term is reported as 8.3%. The percentages are reported as registry values and should not be interpreted as an estimate of comparative risk. The record does not explain whether participants experienced more than one listed event, or provide event-level timing and attribution in the information.
Because this was a single-group, open-label study, these safety figures do not show how often the same events would have occurred in a control group. They also do not establish whether an event was caused by revusiran. The brief summary states that dosing was discontinued and patients were followed for safety, but the reason for discontinuation is not reported in the registry record. These figures describe reported safety experience; they do not establish a comparative safety profile.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase 2, open-label, single-group study of revusiran was conducted in patients with transthyretin-mediated amyloidosis whose disease progressed after liver transplantation. It identifies the primary endpoint as percentage change from baseline in serum TTR at Month 6 and specifies that a negative change represents a reduction. It also reports safety counts and lists secondary outcomes. These registry entries describe the study’s question and selected observations, but they do not supply the primary endpoint estimate.
The primary Month 6 mean, standard deviation, and confidence interval are not reported in the registry record. Consequently, the posted results do not establish the magnitude or direction of the average serum TTR change, or its precision. Results for the listed secondary outcomes are also not reported in the registry record. No conclusion about neurological impairment, quality of life, or disability change can be drawn from outcome titles alone.
Even if a within-group change were available, the study’s single-group design would not provide a randomized comparison. In general, a before-and-after pattern does not isolate the effect of an intervention from other changes over time. This design feature limits causal interpretation, independently of whether the observed measurements changed.
The safety population figures describe events recorded in the study group, including serious adverse events, other adverse events, and deaths. Without a concurrent control group, those counts cannot quantify excess risk attributable to treatment or compare revusiran with another option. The registry record does not report the reason dosing was discontinued, so that circumstance should not be assigned an explanation based on the available information.
In short, the registry record permits a description of the study design, endpoints, and some safety observations. It does not provide the numerical primary efficacy result or the comparative evidence needed to attribute changes or event frequencies to treatment. The distinction between what was measured and what the record reports is central to interpreting this study.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of how design and reporting determine what a result can support. The registry identifies a specific population, intervention, and primary laboratory endpoint, but its single-group, open-label design has no concurrent comparison. A measured change over time could describe the participants’ observed experience, but it would not by itself establish what would have happened without the intervention.
The endpoint is clearly defined in direction: a negative percentage change from baseline at Month 6 means a reduction in serum TTR. Yet the registry record does not report the mean change or its standard deviation. This illustrates why an endpoint definition is not a result. Without the estimate, readers cannot assess magnitude; without a measure of uncertainty, they cannot assess precision. The listed secondary outcomes cannot fill that gap because their results are also not reported in the registry record.
The safety information also shows the difference between event counts in a study population and comparative safety evidence. The record gives counts and percentages for the treated group, but there is no control group against which to compare those observations. The figures therefore have a descriptive role in the available record.
Finally, the stated analysis population depends on Month 6 data being collected. The registry record does not describe missing measurements or their handling. This leaves uncertainty about the endpoint analysis set and its representativeness. Taken together, these features make the study’s statistical contribution depend on careful boundaries: design can define the question, but interpretation also requires reported estimates, uncertainty, analysis details, and a valid comparison when causal claims are at issue.
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 limitation for interpreting the primary outcome is that the registry record does not report its result. Although the primary endpoint is defined as mean percentage change in serum TTR at Month 6 and standard deviation is identified as the dispersion measure, neither statistic is reported. No confidence interval or other precision estimate is reported either. The available record therefore cannot support a quantitative assessment of the primary outcome.
The single-group, open-label design limits comparative interpretation. There is no concurrent control group, and the record lists no allocation or masking. A change from baseline, if reported, would be an observation over time rather than a randomized treatment contrast. The study’s small listed enrollment of 12 also means the safety counts arise from a limited study population; the registry record does not report a control-group comparison.
The primary analysis population requires Month 6 data, but the number with those data and the amount and reasons for missingness are not reported in the registry record. The record also does not report the approach to missing data, detailed statistical methods, interim analyses, or the protocol’s sample-size justification. These omissions prevent assessment of how the primary analysis was implemented and how robust it may be to incomplete follow-up.
Secondary outcomes are named, but their numerical results are not reported in the registry record. The reason dosing was discontinued is also not reported. The safety counts and listed event percentages are descriptive and do not establish comparative risk or treatment causation. These limitations apply to interpretation of the registry record and should not be replaced with assumptions about the protocol or study conduct.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Study of an Investigational Drug, Revusiran (ALN-TTRSC), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Patients Whose Disease Has Continued to Worsen Following Liver Transplant — NCT02595983.
- Registry record last updated 2019-03-28; status last verified 2019-03.
- Results first posted 2019-03-28.
- 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.
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18. Record Summary
The registry record describes a completed phase 2, open-label, single-group study of revusiran in patients with transthyretin-mediated amyloidosis and disease progression after liver transplantation. Enrollment is listed as 12. The primary endpoint was percentage change from baseline in serum TTR at Month 6, with a negative value defined as a reduction. The record does not report the primary endpoint estimate or its precision.
Listed secondary outcomes cover serum TTR over 18 months, neurological impairment, quality of life, and disability stage; their results are not reported in the registry record. The safety population is listed as 12, with 8 affected by serious adverse events, 11 affected in the other adverse-event category, and 2 deaths. Six serious-event terms are listed, each at 8.3%. The single-group design does not provide a concurrent comparison, so the safety figures are descriptive rather than comparative.