A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis (CARES): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis (CARES) (NCT04504825), a randomized phase 3 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

The registry lists additional outcomes spanning health status, walking distance, mortality, cardiovascular hospitalizations, cardiac function and a blood biomarker. These outcomes give the trial a broader focus than the safety endpoint alone, but the outcome names do not establish what the results were. The posted information does not include comparative estimates for those measures.

3. Trial Design

CARES is a Phase 3, randomized, quadruple-masked, parallel-group study. It compares CAEL-101 plus plasma cell dyscrasia treatment with placebo plus plasma cell dyscrasia treatment in patients with Mayo Stage IIIb AL amyloidosis who are naïve to plasma cell dyscrasia treatment. The registry lists an enrollment of 125. This is the registry’s enrollment figure and should not be confused with the group sizes in the posted safety results.

The intervention list includes CAEL-101, placebo and a cyclophosphamide, bortezomib, and dexamethasone regimen. The arm descriptions identify the background therapy as standard-of-care plasma cell dyscrasia treatment. The registry describes CAEL-101 as an intravenous infusion over approximately 2 hours; the placebo group receives normal saline in an equivalent volume. The full details of how background treatment was selected or administered are not reported in the registry record.

The study began on 2020-08-25, and the listed primary completion date is 2025-05-10. Its current status is active, not recruiting. The treatment description says participants were intended to continue double-blind treatment until the last participant was randomized plus 18 months. It also describes the study as having a Primary Evaluation Treatment period, but further details of that period are not reported in the registry record.

Masking is listed as quadruple, but the registry entries do not specify which roles were masked or how masking was maintained. Randomization methods, allocation concealment procedures and the statistical plan are not reported in the registry record. The design therefore establishes the broad comparison, but not the operational details needed to assess those procedures.

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: Subgroup analyses reported for 2 free light chain (FLC) isotypes (Kappa, Lambda) as following subgroups, 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. The sum of the participants for the "CAEL-101 + Plasma Cell Dyscrasia Treatment" Arm/Group in the "Kappa FLC Subtype" and "Lambda FLC Subtype" Rows (25+57=82) appears inconsistent with the number of participants specified in the "Received at Least 1 Dose of Study Drug" Row (84) due to 2 participants were not classified as either kappa or lambda

PETP

Reasons for not completing this period:

OLEP

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat Set: all participants who were randomized. As prespecified, data collected and reported as 'Overall (All Randomized Participants)' and per subgroups 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. For the win-ratio analysis, comparisons were made between participants in the 'CAEL-101 + Plasma Cell Dyscrasia Treatment' arm and the 'Placebo + Plasma Cell Dyscrasia Treatment' arm of each reporting group.

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: Intent-to-treat Set: all participants who were randomized, presented as 'Overall (All Randomized Participants)' and 2 subgroups, 'Kappa FLC Subtype' and 'Lambda FLC Subtype'.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (TEAEs), measured over Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, the primary analysis for the study was conducted 18-47 months after the study randomization.).

The listed primary endpoint is the number of participants with treatment-emergent adverse events, reported as a count of participants. The registry defines an adverse event as an untoward medical occurrence after a participant receives a pharmaceutical product, at any dose, whether or not the occurrence is considered related to treatment. A treatment-emergent adverse event is defined by timing: the event occurs from the first study intervention day through the last study intervention day plus 140 days.

A participant count is a way to summarize how many people experienced an event meeting the endpoint definition. It is not the same as a count of every event, since one participant could have more than one event. The endpoint is intended to describe safety during the defined treatment-emergent period; it does not, by itself, establish whether an event was caused by the study intervention.

Safety endpoints are used to characterize adverse experiences observed during a trial. Their interpretation depends on the event definition, time window, population included and completeness of reporting. Here, the primary endpoint population is the Safety Set: randomized participants who received at least one dose of study intervention. The registry also describes reporting for all Safety Set participants and by Kappa FLC and Lambda FLC subgroups.

The registry directs readers to the reported adverse events section for serious and other adverse events regardless of causality. The primary endpoint’s comparative analysis is not reported in the registry record, so the available counts should not be treated as a complete report of the primary endpoint analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count of participants describe?

A count endpoint records the number of people meeting a stated event definition. For this trial, the endpoint is the number of participants with treatment-emergent adverse events. This differs from counting every adverse event: a person with more than one event is still a participant with an event for a participant-count endpoint. A count also needs a defined population and observation window to be interpretable. The registry specifies the Safety Set and defines the treatment-emergent period in relation to the first and last intervention days.

Counts are descriptive unless paired with an appropriate comparison and uncertainty estimate. The posted serious and other adverse-event figures show how many participants were affected in each group, but those figures alone do not provide an adjusted or unadjusted treatment effect, a confidence interval or a test of a group difference. None of those comparative results for the primary endpoint is reported in the registry record.

Why do event definitions and time windows matter?

An adverse event is not necessarily caused by treatment. The registry definition explicitly includes untoward medical occurrences whether or not they are considered related to the pharmaceutical product. Treatment-emergent status is a timing classification: the event must occur in the specified interval, which extends from the first intervention day through the last intervention day plus 140 days. This definition helps identify events observed during a relevant period, but it does not establish causation.

Follow-up time can differ across participants, particularly in a study where participants were enrolled on a rolling basis. The registry states that the primary analysis was conducted 18-47 months after study randomization. The exact participant-level follow-up durations and their handling in the endpoint analysis are not reported in the registry record. For outcomes affected by time at risk, analysis methods may need to account for how long each participant was observed; the specific method used is not reported.

What can randomization and masking contribute?

In general, random assignment aims to create groups that are comparable on average at the start of a study, including on characteristics that may not have been measured. Masking is generally intended to limit the influence of expectations on treatment delivery, assessments or reporting. CARES is listed as randomized and quadruple-masked, but the roles masked, randomization procedure and allocation concealment details are not reported in the registry record. The design labels alone do not document how these procedures were implemented.

Even with randomization, a result depends on the analysis population, endpoint definition, follow-up and handling of missing observations. The primary endpoint population is the Safety Set, defined as randomized participants who received at least one dose. This is a safety-focused population definition. The registry’s definition does not state which population was used for each efficacy analysis; those analysis populations are not reported in the registry record.

How should the sample-size illustration be read?

The sample-size section is described as a planning illustration computed from an observed effect, not as the trial’s original design calculation. It uses a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustration gives a total number of events; for other outcomes, it gives participants per arm.

Such values describe hypothetical planning requirements under the stated assumptions. They are not evidence that the trial had a particular probability of detecting an effect, and they are not observed power. The registry’s sample-size justification and original design assumptions are not reported in the registry record. A planning illustration based on the observed effect should therefore be read separately from both the trial’s enrollment and the results.

Why does over-dispersion matter in general?

For count outcomes in general, over-dispersion means that observed variability exceeds what a simple model assumes. If a model understates variability, its uncertainty estimates may be too narrow. Appropriate modelling can depend on the outcome distribution, the study design and the intended comparison. The endpoint is described as a participant count, but the analysis model and any assessment of over-dispersion are not reported in the registry record. It would not be appropriate to infer a particular model from the endpoint label alone.

Likewise, a confidence interval and a significance test answer related but distinct questions. A confidence interval communicates uncertainty about an estimated effect; a test evaluates compatibility with a specified null hypothesis under its assumptions. Neither can be reconstructed from the posted group counts without choosing an analysis and making assumptions. No recalculated comparative estimate is presented.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including changes in questionnaire scores, walking distance, cardiac strain, a physical component score and a blood biomarker, as well as mortality and cardiovascular-related hospitalizations. When several outcomes are evaluated, the chance of at least one apparently unusual result can depend on how many tests are conducted and how they are interpreted. Statistical approaches for addressing this issue vary, from prespecified testing sequences to adjustments or clearly exploratory interpretation.

The multiplicity strategy, hierarchy of outcomes, and any adjustment for multiple comparisons are not reported in the registry record. The number of outcome measures and analyses listed in the posted record does not, by itself, reveal whether or how multiplicity was handled. No conclusion about statistical significance across outcomes can be drawn from the outcome list alone.

Missing-data procedures are also not reported in the registry record. The information does not specify how missing questionnaire responses, incomplete follow-up, withdrawals or other absent measurements were handled. For outcomes measured over time, the method for using partial records can affect estimates and uncertainty. No imputation method, sensitivity analysis or missingness assumption is described.

The primary endpoint’s stated population is the Safety Set, comprising randomized participants who received at least one dose. The record also describes reporting overall and by Kappa FLC and Lambda FLC subgroups. These definitions identify the stated safety population and subgroup presentation, but do not explain the population used for each secondary outcome or the analysis rules for subgroup comparisons. Those details are not reported in the registry record.

Accordingly, readers should treat the posted results as a limited record rather than assume that unreported methods were or were not used. A complete interpretation of multiplicity, missing data and analysis populations would require details not present 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: cardiac failure (30.0%), acute kidney injury (22.5%), cardiac arrest (14.3%), pneumonia (14.3%), cardiac failure congestive (8.3%).

The serious adverse-event figures are participant counts in the posted groups. The CAEL-101 plus plasma cell dyscrasia treatment group lists 84 participants at risk and 73 affected; the placebo plus plasma cell dyscrasia treatment group lists 40 at risk and 33 affected. For other adverse events, the corresponding counts are 77 of 84 and 37 of 40. The record also lists 46 deaths and 22 deaths in the respective groups. These figures should be read as reported counts, not as a comparative treatment effect.

Serious adverse events and other adverse events are presented separately, and the registry states that the reported events are regardless of causality. The counts do not establish that the study intervention caused an event. Nor do the counts alone describe event timing, duration, recurrence or severity beyond the serious-event classification. The registry directs readers to the reported adverse events section for event details.

The listed serious-event terms include Cardiac Failure, Acute Kidney Injury, Cardiac Arrest, Pneumonia, Cardiac Failure Congestive and Atrial Fibrillation, each with a percentage shown in the record. The denominator and calculation details for these percentages are not reported in the information, so they should be read as registry-listed values rather than recalculated or compared. Participants may have different event histories, and these term percentages should not be treated as mutually exclusive categories.

The posted safety figures are informative as descriptive reporting, but a full comparative safety interpretation would require a defined analysis, uncertainty estimates and relevant follow-up context. Those are not reported in the registry record.

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

This record describes a randomized, masked Phase 3 comparison in patients with Mayo Stage IIIb AL amyloidosis who were naïve to plasma cell dyscrasia treatment. It shows the study’s stated aim, design, endpoint definitions and selected safety counts. The registry lists overall survival, cardiovascular-related hospitalizations and other measures among the outcomes of interest, but the available information does not report comparative results for those efficacy outcomes.

The serious and other adverse-event counts describe the participants recorded in each group. They do not establish that the treatment caused or prevented an event, and they do not quantify a between-group effect. The reported death counts likewise should not be treated as a survival comparison without an analysis that accounts for follow-up and uncertainty. No such comparative analysis is reported in the registry record.

The absence of a comparative estimate is important. A difference between raw counts could reflect the unequal group sizes, follow-up, underlying outcome patterns or other factors; determining the extent of any treatment effect requires a specified analysis. No new difference or ratio has been calculated from the posted counts. Comparative confidence intervals and tests for the primary endpoint and listed efficacy outcomes are not reported in the registry record.

The outcome definitions also matter. The primary endpoint counts participants with treatment-emergent adverse events over a specified interval, while the registry’s posted safety section separates serious from other events. Those descriptions are related to safety but do not constitute a reported primary endpoint comparison. The population used for the primary safety outcome is defined, while analysis populations for the listed efficacy outcomes are not reported in the registry record.

In short, the posted information supports a description of trial design and recorded safety counts, not a conclusion about efficacy or a definitive comparative safety effect. Readers should distinguish the trial’s purpose from its reported results and should not interpret missing comparative analyses as evidence for either benefit or lack of benefit.

13. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a broad clinical objective and the limited comparative results available in the registry information. The stated purpose includes survival, cardiovascular-related hospitalizations, safety and tolerability, while the listed primary endpoint is a count of participants with treatment-emergent adverse events. The outcome list also spans patient-reported measures, physical function, cardiac measures and a blood biomarker. Each type of outcome raises different questions about definition, follow-up, analysis and precision.

The randomized, quadruple-masked, parallel-group design establishes an intention to compare assigned groups under masking. But design labels do not substitute for the analysis plan or results. Without comparative estimates and uncertainty intervals, readers cannot assess the size or precision of any treatment effect from the posted counts alone. That distinction is especially important when the visible safety information is descriptive and the primary endpoint is not reduced to a single comparison.

The record also illustrates why the analysis population and observation window belong in any safety interpretation. The Safety Set includes randomized participants who received at least one dose, and the endpoint definition extends beyond the last intervention day. These choices define what observations count, but further details about follow-up and analysis are not available.

Finally, the sample-size section should be kept separate from the trial design. It is a planning illustration based on an observed effect and stated assumptions, not a record of the original design justification or evidence of observed power. Keeping descriptive counts, inferential analyses and planning illustrations distinct is essential to reading clinical trial statistics accurately.

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 available registry information does not include comparative estimates, confidence intervals or significance tests for the listed primary endpoint or the efficacy outcomes. This prevents assessment of the magnitude and precision of any between-group effect from the details. The primary endpoint is described as having several categories or time points and is not reduced to one comparison.

The group sizes in the safety results are not identical, and the record does not provide a comparative analysis that accounts for follow-up or other features of the outcome data. The registry reports the primary analysis as occurring 18-47 months after study randomization, but participant-level follow-up, censoring details and analytic handling of time are not reported in the registry record. The death counts therefore cannot be interpreted as a survival estimate on their own.

The primary endpoint has a defined Safety Set, but analysis populations for secondary outcomes are not reported in the registry record. Missing-data methods, sensitivity analyses, multiplicity handling and subgroup analysis procedures are also not reported. The registry identifies Kappa FLC and Lambda FLC subgroups for safety reporting, but their analysis details are not available.

Further details of randomization, allocation concealment and the roles covered by quadruple masking are not reported in the registry record. The registry lists a plasma cell dyscrasia regimen among interventions, but the available arm descriptions do not fully specify background-treatment use or variation. The listed top serious-event percentages have no denominator details in the information.

These limitations concern what can be concluded from the record details, not necessarily what was done during the full study. The sample-size illustration cannot fill these gaps: it is based on the observed effect and stated assumptions, while the original sample-size justification and statistical plan are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis (CARES) — NCT04504825.
• Registry record last updated 2026-07-02; status last verified 2026-06.
• Results first posted 2026-07-02.
• 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

CARES is a Phase 3 randomized, quadruple-masked, parallel-group study of CAEL-101 plus plasma cell dyscrasia treatment versus placebo plus plasma cell dyscrasia treatment in treatment-naïve patients with Mayo Stage IIIb AL amyloidosis. The registry lists enrollment of 125 and status as active, not recruiting. The primary endpoint is the number of participants with treatment-emergent adverse events in the Safety Set.

The posted safety figures list serious adverse events in 73 of 84 participants in the CAEL-101 group and 33 of 40 in the placebo group, other adverse events in 77 of 84 and 37 of 40, and 46 and 22 deaths, respectively. These are descriptive counts; comparative endpoint analyses and efficacy estimates are not reported in the registry record. The registry’s stated aims include survival, cardiovascular-related hospitalizations, safety and tolerability.