Multiple Treatment Session Study to Assess GSK2398852 Administered Following and Along With GSK2315698: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multiple Treatment Session Study to Assess GSK2398852 Administered Following and Along With GSK2315698 (NCT03044353), a non-randomized phase 2 study. The primary outcome is Change From Baseline in Left Ventricular (LV) Mass Over Time up to 8-week Follow-up.

2. Clinical Question

The study asked whether repeated anti-SAP treatment was associated with a reduction in cardiac amyloid load in people with cardiac amyloidosis, and whether changes in amyloid load were accompanied by changes in cardiac function. Cardiac magnetic resonance imaging was used to assess left ventricular mass as the primary endpoint. Echocardiography was also identified in the study summary as a method for monitoring cardiac status.

The planned treatment involved GSK2315698, also called CPHPC, and GSK2398852, an anti-SAP monoclonal antibody. The summary describes monthly repeat courses in which GSK2315698 was followed by GSK2398852. The study title also refers to administration following and along with GSK2315698. Participants could receive up to 6 courses.

The study included three clinical groups: people with transthyretin cardiomyopathy, people with AL amyloidosis who were more than 6 months after chemotherapy, and people with newly diagnosed AL amyloidosis undergoing chemotherapy. Its objectives included evaluating the cardiac imaging endpoint across the groups and assessing safety and tolerability, including compatibility with chemotherapy for people with AL amyloidosis.

The registry record does not report numerical changes in left ventricular mass, comparative estimates, or an analysis of whether imaging changes were associated with cardiac function. It therefore describes the question the study was intended to address, but does not provide results that resolve it.

3. Trial Design

This was a phase 2, open-label, non-randomized, parallel-group study sponsored by GlaxoSmithKline. The registry record lists an enrollment of 7 and a status of terminated. The recorded study start was 2017-07-10, and the primary completion date was 2019-01-03. The reason for termination is not reported in the registry record.

Three clinical groups were planned. Group 1 comprised participants with cardiac transthyretin amyloidosis, including people with mutant genotypes primarily associated with familial amyloidotic cardiomyopathy and people with wild-type transthyretin. Group 2 comprised people with AL amyloidosis who had attained a very good partial response or complete response to systemic chemotherapy, including autologous stem cell transplantation. Group 3 comprised newly diagnosed Mayo stage II/IIIa AL participants who attained a free light chain complete response during the first 3 cycles of first-line chemotherapy, where the first cycle was CyBorD.

The study summary describes monthly repeat anti-SAP treatment, with GSK2315698 followed by GSK2398852, and a maximum of 6 courses. Maximum total time in the study was described as approximately 18 months. The title also refers to administration following and together with GSK2315698. The exact treatment schedule for each participant and the details of any deviations from that schedule are not reported in the registry record.

Because allocation was non-randomized and masking was absent, the groups should not be read as randomized treatment arms or as a like-for-like control comparison. Their clinical characteristics and chemotherapy context differ by design. The registry record does not report a separate untreated control group, random assignment procedure, or blinding. It also does not report the protocol's sample-size justification, a detailed statistical analysis plan, or interim analysis procedures. The small enrollment and the inclusion of distinct patient groups are important context for interpreting any estimates that might be reported; numerical primary endpoint results are not reported in the registry record.

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: Twelve participants were screened; seven were enrolled in to study (six were enrolled in Group 1 and one in Group 2). No participant was enrolled in Group 3. The study was terminated by sponsor due to a change in the benefit:risk profile of GSK2315698+GSK2398852 (anti-SAP treatment).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

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.

Population: No participant was enrolled in "Group 3: Newly diagnosed Mayo stage II/IIIa AL participant" due to early termination of the study.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Left Ventricular (LV) Mass Over Time up to 8-week Follow-up, measured over Baseline (Day -1) and Session 2 Day 24, Session 3 Day 24, Session 4 Day 24, Session 5 Day 24, 8 Weeks Follow-up.

The primary endpoint was change from baseline in left ventricular mass over time up to 8-week follow-up, measured in grams by cardiac magnetic resonance imaging. The listed time points were baseline on Day -1, Session 2 Day 24, Session 3 Day 24, Session 4 Day 24, Session 5 Day 24, and 8 Weeks Follow-up. Change was defined as the post-dose visit value minus the baseline value. Baseline was the latest assessment before the first administration of either study drug.

Left ventricular mass was selected as an imaging measure intended to assess reduction in cardiac amyloid load. The study summary also framed reduction in cardiac amyloid load and possible improvement in cardiac function as objectives. In general, a repeated-measures endpoint can describe how a measurement changes across scheduled visits, rather than only comparing one post-treatment measurement with baseline. The interpretation depends on the observed values, the number of participants assessed at each time point, and how missing measurements are handled.

The registry record describes the measurement and its intended purpose but does not report the numerical baseline or follow-up means, standard deviations, changes, confidence intervals, or hypothesis tests. It therefore does not establish the direction, magnitude, or precision of change in left ventricular mass.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a change-from-baseline endpoint mean?

The endpoint is defined as the post-dose visit value minus the baseline value. In general, this expresses each post-baseline measurement relative to that participant's own starting measurement. A negative value would mean the measured value was lower than baseline, while a positive value would mean it was higher; this is a general interpretation of the subtraction definition, not a claim about results in this study. The registry record does not report the actual changes.

The primary measure is continuous: left ventricular mass in grams, with a mean and standard deviation specified as the summary statistics. In general, a mean describes the average value in the analyzed group, while a standard deviation describes how spread out individual values are around that average. A mean alone does not show how variable the measurements were or how precisely the group mean was estimated. The registry record does not report the endpoint means or standard deviations.

Why assess more than one time point?

The listed endpoint times span baseline, several treatment sessions, and follow-up. In general, repeated assessments can help describe whether a measure changes over time and whether a change is maintained at a later assessment. They also raise analytic issues: measurements from one participant are related to one another, and the number of participants with available measurements may differ by visit. Appropriate analysis may account for within-participant correlation, but the method used for this endpoint is not reported in the registry record.

The primary endpoint description says that only participants with data available at the specified time points were analyzed and indicates that participant counts were intended to appear in category titles. The recorded titles contain an “n= X” placeholder rather than actual counts. The record does not state whether the analysis used a separate available-case mean at each visit, a repeated-measures model, or another approach. It also does not report an imputation method or sensitivity analysis for missing values.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data under the analysis assumptions and conveys uncertainty around an estimate. A narrower interval indicates greater precision than a wider interval, while neither width nor position alone establishes clinical importance. The primary endpoint's confidence intervals are not reported in the registry record, so its precision cannot be evaluated. No new interval can be reconstructed from the record because the relevant endpoint estimates and dispersion values are absent.

How should hypothesis tests be read?

In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions were true. It is not the probability that the null hypothesis is true and does not measure the size or importance of an effect. No primary endpoint p-value or test is reported in the registry record. The record also does not describe the planned hypothesis, significance threshold, or whether the primary analysis was intended as a formal confirmatory test.

What is the implication of the non-randomized design?

In general, random assignment helps balance measured and unmeasured prognostic factors between treatment groups. Without randomization, differences in patient characteristics, disease course, treatment context, or selection into a group can contribute to differences in observed outcomes. This study is listed as non-randomized and open-label, with groups defined by disease type and chemotherapy context. The groups therefore do not constitute a randomized treatment comparison. Any within-group change, if reported, would be descriptive unless supported by additional design and analysis features; those features are not reported in the registry record.

Open-label means that masking was absent. In general, knowledge of treatment can affect care, participant experience, or assessment. Cardiac magnetic resonance is an imaging measure, but the record does not report whether image readers were centrally assessed or blinded to visit order or participant group. Such procedures should not be assumed.

What do the planning illustrations mean?

In general, sample-size planning illustrations use assumptions about the target effect, significance level, allocation, and statistical model to show how many participants might be needed for a specified power under those assumptions. They are not observed results and do not establish the power achieved by a completed study. The registry record states that its planning illustration is based on an observed effect, uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a stated fraction of the observed effect. It also specifies that non-time-to-event illustrations express participants per arm, while time-to-event illustrations express total events. These are planning assumptions, not the trial's own design justification; that justification is not reported in the registry record. No planning output or protocol rationale should be treated as evidence about the primary endpoint results.

Finally, the registry lists 40 outcome measures and 0 analyses. In general, multiple endpoints and repeated time points require clear reporting of which analyses were prespecified and how multiplicity was handled. The statistical plan and multiplicity approach are not reported in the registry record. The outcome count alone does not reveal which outcomes were prioritized, how tests were conducted, or whether any adjustment was made.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 40 outcome measures, including the primary left ventricular mass endpoint and secondary measures involving skin biopsies, blood biomarkers, plasma cytokines, and complement markers. It lists 0 analyses. The multiplicity strategy and any hierarchy among outcomes are not reported in the registry record.

In general, when many outcomes, visits, or subgroup assessments are examined, the chance of at least one apparently unusual result can increase. Prespecifying a primary endpoint and a testing hierarchy, or applying an adjustment, can help clarify the interpretation of multiple tests. The record identifies a primary endpoint, but does not describe how results across the many listed measures were to be interpreted together. Numerical primary endpoint results and inferential analyses are not reported in the registry record.

Missing-data handling is also incompletely described. The primary endpoint population is defined as participants who received at least one dose of either study treatment, and the endpoint text says that only participants with data available at specified time points were analyzed. The actual numbers assessed at each time are not reported in the registry record; category titles contain an “n= X” placeholder. The record does not report reasons for missing measurements, an imputation procedure, assumptions about missingness, or sensitivity analyses.

In general, an available-data analysis uses the measurements observed for a particular assessment, whereas imputation or longitudinal models may make use of additional assumptions about incomplete follow-up. Missingness can affect both precision and interpretation, especially if participants without measurements differ systematically from those with measurements. The record does not provide enough information to assess whether that concern arose or how it was addressed.

The safety population is defined as participants receiving at least one dose of any study treatment. The relationship between that population and the analyzed endpoint counts at each time point is not reported in the registry record. The record also does not report an intention-to-treat population or a detailed analysis-population plan.

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: vasculitis (100.0%), transient ischaemic attack (16.7%), cardiac failure (16.7%).

The safety listing gives results for two groups. In group 1, 2 of 6 participants at risk were reported as affected by serious adverse events, and 6 of 6 were affected by other adverse events. In group 2, 1 of 1 was reported as affected by serious adverse events, and 1 of 1 by other adverse events. The listed number of deaths was 0 in each of these groups. No corresponding group 3 safety entry appears in the registry record.

The registry also lists serious adverse-event terms with percentages: vasculitis at 100.0%, transient ischaemic attack at 16.7%, and cardiac failure at 16.7%. The denominator and counting method for these term percentages are not reported in the registry record. They should not be read as rates among all enrolled participants or used to infer how many individuals experienced each term without that denominator.

In general, “at risk” indicates the group count used for the listed safety summary, while “affected” indicates participants recorded with the relevant event category. These are descriptive counts; they do not by themselves establish causality, comparative risk, or the completeness of adverse-event ascertainment. The open-label, non-randomized design and small group sizes also mean that comparisons between groups would not be like-for-like randomized comparisons. The registry record does not report event timing, severity beyond the serious-event classification, relatedness assessments, exposure-adjusted rates, or detailed follow-up for the listed safety results.

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

The record establishes that a phase 2 study was designed to assess repeated anti-SAP treatment in people with cardiac amyloidosis and that left ventricular mass by cardiac magnetic resonance was its primary endpoint. It also documents the planned clinical groups, the repeated-treatment concept, the outcome time points, and a safety population definition. Those details clarify what the investigators intended to measure.

It does not establish whether left ventricular mass decreased, increased, or remained similar to baseline. Numerical endpoint results, variability estimates, confidence intervals, and primary analysis results are not reported in the registry record. Without these values, the magnitude and precision of any change cannot be evaluated, and no conclusion about the endpoint can be drawn from the registry record alone.

Even if numerical within-group changes were available, the non-randomized, open-label design would not by itself show that treatment caused those changes. The three groups differ in disease type and chemotherapy context, and no randomized control group is described. Natural changes in disease, concurrent care, selection, and other factors could contribute to observed patterns. The registry record does not describe an adjustment strategy that would address these issues.

The safety listing records adverse events in two groups and gives counts for serious and other adverse events, but it does not establish that a listed event was caused by either study drug. The term percentages have no reported denominator in the registry record, and group 3 safety figures are not shown. These limitations prevent a complete interpretation of safety across the full enrolled study population.

In general, a registry entry is most informative when it reports the prespecified outcomes, participant counts, estimates of effect, uncertainty, and analysis methods. Here, the study's stated objectives and endpoint definitions are available, while numerical primary outcome results and key analytic details are not reported in the registry record. The study status is listed as terminated, but the reason is not reported; the status alone does not explain why the study ended or what conclusions its investigators reached.

13. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between a clearly defined endpoint and a reported result. The registry identifies a continuous imaging measure, a baseline definition, a subtraction rule for change, and scheduled assessments through follow-up. Those elements make the intended measurement understandable. But without observed values, participant counts at each assessment, and uncertainty estimates, readers cannot determine the size or precision of the endpoint changes.

The study also highlights the limits of interpreting small, non-randomized clinical groups. Enrollment was 7, and the study included distinct amyloidosis and chemotherapy contexts. In general, a small study can provide descriptive information but will often have limited precision, particularly when follow-up measurements are incomplete or participants are divided among groups. The record does not report a sample-size justification or enough outcome data to quantify the precision actually achieved.

Its repeated-measures structure raises practical issues common to longitudinal studies: measurements within a participant are correlated, available participant counts can change over time, and missing outcomes may affect interpretation. The record defines an available-data approach in broad terms but does not identify the statistical model, missing-data assumptions, or sensitivity analyses. These omissions make it difficult to assess how robust any potential longitudinal pattern would be.

Finally, the registry lists many outcomes and no analyses. This makes transparent reporting of endpoint prioritization and multiplicity especially relevant. Without a reported analysis plan and numerical results, readers cannot distinguish confirmatory conclusions from exploratory descriptions. The record is therefore useful for understanding the question and intended design, but not for judging the primary endpoint's observed effect or its statistical uncertainty.

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 primary limitation is the absence of numerical primary endpoint results in the registry record. No visit-specific means, standard deviations, changes from baseline, confidence intervals, or p-values are reported. The number of participants with available imaging data at each time point is also not reported; the outcome description retains an “n= X” placeholder.

The small enrollment of 7 limits the amount of information available for estimating outcomes, and the study's three groups represent different clinical settings. The record does not report the number enrolled or treated within group 3 in the safety listing, and no group 3 adverse-event counts are shown there. The reason the study was terminated is not reported in the registry record.

The design was open-label and non-randomized. There is no randomized control group described, so any observed change over time would not isolate a treatment effect from other influences. The registry does not report blinded image assessment, detailed treatment exposure, participant-level follow-up, or methods for adjusting for differences between groups.

Other important analytic details are absent: the statistical model for repeated measurements, the handling of missing values, sensitivity analyses, a multiplicity strategy, and a protocol-based sample-size justification are not reported in the registry record. Although the record lists 40 outcome measures, it lists 0 analyses. These omissions constrain evaluation of both the prespecified analysis and the completeness of outcome reporting.

Safety interpretation is limited by the lack of a group 3 listing and by the absence of denominators and counting details for the serious-event term percentages. The listed counts are descriptive and do not establish causality. The registry record also does not report the duration of safety follow-up by participant or whether all adverse events were captured over the same exposure period.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Multiple Treatment Session Study to Assess GSK2398852 Administered Following and Along With GSK2315698 — NCT03044353.
• Registry record last updated 2019-10-16; status last verified 2019-09.
• Results first posted 2019-10-16.
• 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

NCT03044353 was a GlaxoSmithKline-sponsored, phase 2, open-label, non-randomized, parallel-group study in cardiac amyloidosis. The registry lists enrollment of 7 and status as terminated. The recorded study start was 2017-07-10, and primary completion was 2019-01-03; the reason for termination is not reported in the registry record.

The study planned repeated treatment with GSK2315698 and GSK2398852, with up to 6 courses, across transthyretin cardiomyopathy and two AL amyloidosis groups. Its primary endpoint was change from baseline in left ventricular mass by cardiac magnetic resonance over the listed treatment and follow-up assessments.

The registry record describes the endpoint but does not report its numerical results or the actual participant counts at each assessment. Safety counts are listed for two groups, with 0 deaths in each; a corresponding group 3 safety entry is not reported. The record lists 40 outcome measures and 0 analyses, while the statistical analysis plan, multiplicity approach, and sample-size justification are not reported in the registry record.