Study of AG10 in Amyloid Cardiomyopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of AG10 in Amyloid Cardiomyopathy (NCT03458130), a randomized phase 2 study. The primary outcome is Change in Diastolic Blood Pressure.

2. Clinical Question

The study was designed to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of AG10 compared with placebo. Its listed secondary outcomes include threshold levels of overall stabilization measured by fluorescent probe exclusion and steady-state trough concentration of AG10. These outcomes address different aspects of the study: stabilization is a pharmacodynamic measure, while trough concentration is a pharmacokinetic measure. Neither can substitute for a reported result on the primary blood-pressure outcome.

The clinical question is therefore about the short-term measurements specified in the registry, not about long-term clinical outcomes. The record describes a 28-day blinded treatment period and does not report outcomes beyond that period. It also does not report an analysis comparing the two AG10 doses with one another or with placebo.

3. Trial Design

This was a Phase 2, randomized, placebo-controlled, dose-ranging study of AG10 in participants with symptomatic transthyretin amyloid cardiomyopathy. The record lists familial ATTR-CM and wild-type ATTR-CM as the conditions studied. It reports an enrollment of 49 and a parallel-group design. Participants were assigned to one of two AG10 dose groups or placebo; the arm descriptions specify AG10 400mg twice daily, AG10 800mg twice daily, and placebo twice daily, each for 28 days.

The study description says treatment was given against a background of stable heart failure therapy. The registry lists masking as quadruple, while the brief summary describes the study as double-blind. The record does not explain how masking was implemented or which parties were masked. It describes the study as prospective and multicenter, and says screening and randomization were followed by a 28-day blinded, placebo-controlled treatment period.

The registry lists the study as completed. It gives a start date of 2018-04-27 and a primary completion date of 2018-10-05. Those dates describe the study record; they do not establish when any particular participant completed treatment or when analyses were conducted.

The stated emphasis is safety, tolerability, pharmacokinetics and pharmacodynamics. The primary outcome is change in diastolic blood pressure from baseline to Day 28, postdose. Secondary outcomes include stabilization thresholds assessed by fluorescent probe exclusion and steady-state trough concentration of AG10. The registry record does not report the allocation ratio, site count, eligibility criteria in detail, treatment adherence, or the full schedule of assessments.

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

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 Change in Diastolic Blood Pressure, measured over Baseline to Day 28.

The primary outcome is the change in diastolic blood pressure from baseline to Day 28, measured postdose, in mm Hg. Diastolic blood pressure is the lower pressure value recorded during a heartbeat cycle. A change score represents how that measurement differs from a participant’s baseline value at the specified follow-up assessment.

The registry identifies the outcome summary as a mean with standard deviation. In general, a mean describes the central value of a set of measurements, while a standard deviation describes how spread out those measurements are around the mean. Considering change from baseline focuses the outcome on within-participant movement over the treatment period, rather than on a single follow-up measurement alone.

Blood pressure is a physiological measure, and its inclusion gives a quantified measure for the short treatment period. The record does not state why this measure was selected as the primary endpoint or what direction or size of change was considered important. It also does not report the mean changes, standard deviations, confidence intervals, or a statistical comparison among the treatment groups. Consequently, the endpoint can be described, but its results and their precision cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary outcome summarize?

The primary outcome is a continuous measure: change in diastolic blood pressure from baseline to Day 28, postdose. The registry specifies a mean and standard deviation. In general, the mean summarizes the average measured change, while the standard deviation describes participant-to-participant spread around that average. Neither statistic alone gives the treatment contrast. To assess a randomized comparison, readers would also need the group-specific outcome estimates and a comparison between groups.

The registry record does not report the values needed to describe the observed primary outcome. It provides no group mean changes or standard deviations, and no estimated between-group difference. A change score and a group contrast answer related but distinct questions: a group’s mean change describes movement within that group, while the contrast describes how the average changes differ between randomized groups. The latter is generally the central quantity for interpreting a treatment comparison.

How should uncertainty be considered?

General statistical explanation: a confidence interval describes a range of values reasonably compatible with the data and the analysis assumptions. Its width conveys precision: a narrower interval indicates more precision than a wider interval. A p-value, when reported, assesses how compatible the data are with a specified null hypothesis under the statistical model. Neither a p-value nor an interval measures clinical importance on its own. For this study, the registry record does not report a confidence interval or p-value for the primary outcome, so neither statistical significance nor precision can be assessed from the recorded information.

Standard deviations are measures of variability among participant measurements; they are not confidence intervals for the mean or for a group difference. General statistical explanation: estimates from small groups can be imprecise, and the amount of imprecision depends on factors including the observed variability and analysis. No confidence interval or other precision estimate for the primary endpoint is reported, so the uncertainty of its results cannot be quantified from this record.

What does randomization contribute?

General statistical explanation: random assignment is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. It supports a fair comparison when the assigned groups are analyzed appropriately. It does not guarantee that groups will be identical, especially in a study with limited enrollment, and it does not remove the need to report outcome results, missing data, or the analysis population. The registry record says the study was randomized but does not report the allocation ratio or enough analysis details to assess how the randomization was used in the primary analysis.

The design is described as parallel-group and placebo-controlled. The two AG10 regimens and placebo were planned as distinct arms over the 28-day treatment period. The record labels masking as quadruple and also describes the study as double-blind, but does not explain which people were masked or how masking was maintained. Further operational details are not reported in the registry record.

How should the planning illustrations be read?

The stated sample-size assumptions describe planning illustrations based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, the description says the illustration uses total events; for other outcomes, it uses participants per arm. These are general calculation assumptions, not a report of the trial’s actual design rationale.

General statistical explanation: a planning calculation asks how many participants might be needed under chosen assumptions about an effect, variability, allocation and statistical threshold. Changing the assumed effect changes the resulting planning requirement. Such figures are illustrations rather than observed power: observed power is not a substitute for reporting an effect estimate and its uncertainty. The registry record does not report the trial’s own sample-size justification or indicate that the illustration assumptions were used to determine enrollment.

The primary outcome is not presented as a single comparison in the posted results, and its numerical effect is not reported. Therefore, any illustration tied to a fraction of an observed effect should not be treated as evidence about the primary endpoint. The record does not identify an observed primary effect on which to base such an interpretation.

What can be inferred from the outcome listing?

The record lists seven outcome measures, but the number of analyses is recorded as zero. That is not a report of null findings; it means the record does not contain analysis results in the available entry. The listed outcome definitions help identify what was intended to be measured, but outcome definitions do not show what participants experienced. For the primary endpoint, interpretation would require numerical results and an analysis description, neither of which is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, spanning the primary blood-pressure measure and secondary pharmacodynamic and pharmacokinetic measures. It does not report how the study handled the possibility of multiple outcomes, multiple dose comparisons, or repeated assessments. A multiplicity adjustment, a hierarchy among outcomes, or another prespecified approach is not reported in the registry record. Without that information, the record does not establish how statistical error across multiple tests was controlled, if at all.

Missing-data methods are also not reported. The record does not state how missing Day 28 blood-pressure measurements, withdrawals, or incomplete assessments were handled, or whether any imputation or sensitivity analysis was used. The enrollment figure does not identify how many participants contributed to each outcome analysis. Although adverse-event group sizes are listed, those counts cannot be assumed to be the analysis populations for the primary endpoint.

The primary outcome’s population field is blank. The registry record does not identify whether the primary analysis used all randomized participants, participants who received treatment, participants with available measurements, or another population. It also does not report whether participants were analyzed according to randomized assignment or describe exclusions from an analysis.

These omissions limit the ability to evaluate how the reported endpoint would have been analyzed and how robust a treatment comparison might be to incomplete data or multiple testing. No assumptions about a statistical analysis plan, interim analyses, missing-data strategy, or analysis population can be inferred from the study design description alone.

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 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnoea (6.2%), atrial fibrillation (5.9%), cardiac failure congestive (5.9%), cellulitis (5.9%).

The registry reports serious adverse events for each of the three groups. For AG10 400mg, 16 participants were at risk and 1 was affected by a serious adverse event. For AG10 800mg, 16 were at risk and 0 were affected. For placebo, 17 were at risk and 2 were affected. The record reports 0 deaths in each group. These are participant counts as listed in the registry, not estimates of comparative risk.

The record also reports other adverse events: 10 participants in the AG10 400mg group, 11 in the AG10 800mg group, and 15 in the placebo group were affected, with the listed at-risk counts of 16, 16, and 17, respectively. These counts are distinct from the serious adverse-event counts in the record. They do not establish that events were caused by study treatment, and they should not be read as a treatment-effect comparison.

The registry lists dyspnoea at 6.2%, atrial fibrillation at 5.9%, cardiac failure congestive at 5.9%, and cellulitis at 5.9% among its top serious terms. The record does not provide enough detail to interpret those percentages by treatment group or to establish how the terms relate to the participant counts. Small group counts and the short treatment period also limit what can be concluded from these figures. The record does not report detailed event timing, severity grading beyond seriousness, relatedness assessments, or exposure-adjusted summaries.

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

The registry record describes what the study was set up to examine: short-term safety, tolerability, pharmacokinetics and pharmacodynamics of AG10 compared with placebo in participants with symptomatic transthyretin amyloid cardiomyopathy. It specifies two AG10 doses, a placebo group, a 28-day treatment period, and change in diastolic blood pressure as the primary outcome. These details establish the study question and design, not the answer to the primary question.

The record does not report the primary outcome results. It gives no observed mean change in diastolic blood pressure, no group comparison, and no uncertainty interval. The available information therefore cannot show the direction or size of any primary-outcome difference, or how precisely it was estimated. Completion of the study and enrollment of 49 participants do not fill that reporting gap.

The safety counts describe participants affected by reported adverse events during the study as recorded. They are not, by themselves, proof that an event was caused by a study treatment or that one group had a higher underlying risk. The registry’s short follow-up period and lack of detailed comparative analyses further limit interpretation of the safety information.

The listed secondary outcomes point to additional pharmacodynamic and pharmacokinetic questions, but their numerical findings are not reported in the registry record. Definitions such as stabilization thresholds are not evidence that participants reached those thresholds. Likewise, no clinical outcome beyond the stated study measures can be inferred from the title or rationale.

The study can be understood as a randomized, placebo-controlled dose-ranging investigation with a defined short-term endpoint and reported safety counts. It cannot be used, from the available registry results, to quantify an effect on the primary measure, judge the precision of a treatment contrast, or make conclusions about longer-term outcomes. Those questions require outcome results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable for setting out a randomized, placebo-controlled comparison across two AG10 dose groups and placebo, while defining a continuous primary outcome measured as change from baseline. That structure makes the intended comparison clear: the dose groups can be considered alongside a concurrent placebo group over the same 28-day treatment period. The presence of two dose levels also makes it important to know how comparisons among arms and multiple outcomes were planned and reported.

The registry record illustrates the distinction between trial design information and trial results. Randomization, masking, the endpoint definition and enrollment describe how a study was organized. They do not establish an effect or its precision. In this record, the primary endpoint is named but its numerical results and comparison are not reported, so readers cannot use the design alone to evaluate that outcome.

The study also has several types of outcomes with different interpretations. A blood-pressure change is a continuous physiological measure; stabilization thresholds are pharmacodynamic; and trough concentration is pharmacokinetic. These address different questions and should not be treated as interchangeable evidence. Their multiplicity makes transparent reporting of analysis methods especially useful, but the registry record does not describe an adjustment or hierarchy among outcomes.

Finally, the safety counts offer a reminder that participant counts and comparative inference are not the same. Counts can describe what was recorded in each group, but a fuller comparison depends on event definitions, exposure, follow-up, and analysis details. The record is therefore informative about the trial’s planned structure and the types of measurements collected, while leaving key statistical questions about results and analysis unanswered.

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 this trial from the registry record is that it does not report numerical results for the primary endpoint. No group-specific mean changes, standard deviations, estimated contrasts, confidence intervals, or p-values are reported. Without those, the effect and its precision cannot be assessed.

The record lists enrollment of 49, but does not give group sizes for the primary endpoint analysis or state how many participants contributed data at baseline and Day 28. The population field for the primary outcome is blank. It does not report analysis exclusions, adherence, missingness, or methods for handling missing measurements. Adverse-event group counts should not be assumed to describe the primary outcome population.

Although the study is described as randomized, placebo-controlled, parallel-group and masked, the registry does not provide the allocation ratio or explain masking procedures. It labels masking as quadruple in one field, while the summary uses double-blind language. The record does not reconcile those descriptions. It also does not provide detailed eligibility criteria, site information, or a full assessment schedule.

The stated study focus includes safety, tolerability, pharmacokinetics and pharmacodynamics, but the numerical results for the listed secondary outcomes are not reported in the available record. The record also does not describe the statistical analysis plan, multiplicity handling, interim analyses, or the trial’s sample-size justification. A planning illustration based on observed-effect assumptions is not a substitute for that design rationale or for actual outcome estimates.

The reported safety counts are limited to the listed group-level participant counts and selected serious-event terms. Further details about timing, severity, attribution, exposure, and comparative analysis are not reported in the registry record. The short, 28-day treatment period also means the record does not describe longer-term outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of AG10 in Amyloid Cardiomyopathy — NCT03458130.
• Registry record last updated 2022-11-16; status last verified 2022-10.
• Results first posted 2022-11-16.
• 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

NCT03458130 is a completed Phase 2 randomized, placebo-controlled, dose-ranging study of AG10 in symptomatic transthyretin amyloid cardiomyopathy. The record reports enrollment of 49 and describes a parallel-group study with AG10 400mg twice daily, AG10 800mg twice daily, or placebo twice daily for 28 days, on a background of stable heart failure therapy.

The primary outcome is change in diastolic blood pressure from baseline to Day 28, postdose, summarized as a mean with standard deviation. Listed secondary outcomes concern stabilization thresholds and steady-state trough concentration. Serious adverse-event counts and selected serious terms are recorded by group.

The primary outcome’s numerical results, treatment comparisons, precision estimates, analysis population, missing-data approach, and multiplicity strategy are not reported in the registry record. The posted information therefore describes the study design and selected safety counts, but does not permit interpretation of the primary treatment comparison.