Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis (CARES) (NCT NCT04512235)

This study consisted of 2 periods: the Primary Evaluation Treatment Period (PETP) and the Open-label Extension Period (OLEP). Primary analysis data reported based only on data collected through the end of the participant's PETP (last participant in \[LPI\] plus 18 months). Final data will be reported after study completion.

Subgroup analyses reported for 2 free light chain (FLC) isotypes (Kappa, Lambda) as following subgroups, 'Kappa FLC Subtype' and 'Lambda FLC Subtype'.

Data reported for Overall participants and for 2 FLC subtypes (Kappa and Lambda).

Time to all-cause mortality was defined as the number of weeks from the date of randomization to the date of death if it is on or before the end of PETP. Participants alive at the end of PETP (LPI+18 months) were censored at their last known alive date recorded within the PETP. CVHs were events adjudicated and confirmed as such by the Clinical Event Adjudication Committee (CEAC). Hypothesis testing with the Finkelstein-Schoenfeld test and treatment effect estimation with the win-ratio method based on pairwise comparisons of participant outcomes with comparisons performed in a hierarchical manner. To calculate win ratio, participant outcomes based on time to all-cause mortality were first compared and if there was no 'winner' due to censoring then a comparison based on frequency of cardiovascular hospitalization was made. A win ratio \>1 represents a more favorable outcome for CAEL-101 over placebo.

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, at any dose, that was not necessarily related to the treatment. A TEAE was an AE with an occurrence defined as follows: last study intervention day-first study intervention day + 140 days. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

The KCCQ-OS is a 23-item self-administered questionnaire that quantifies physical function, symptoms, social function, self-efficacy and knowledge and quality of life. It uses an ordinal, adjectival (Likert) scale. Participants provide their level of agreement or disagreement with an agree-disagree scale for a series of statements. The questionnaire captures how the participants feel physically. The overall score was calculated as the sum from all 23 items and ranges from 0 to 100, where higher scores reflected better health status (fewer symptoms, fewer social or physical limitations, and better quality of life).

The 6MWT measures the distance a participant can quickly walk on a flat, hard surface in a period of 6 minutes. It evaluates the global and integrated response of all the systems involved during exercise. This is a self-paced test; participants choose their own intensity of exercise and are allowed to stop and rest during the test.

All-cause mortality was defined as death on or before the end of the PETP. Otherwise, participants who were alive at the end of the PETP (last participant randomized plus 18 months) were censored at their last known alive date recorded within the PETP. All deaths, regardless of causality or whether they were reported as a reason for study discontinuation, are reported in the All-Cause Mortality section.

CVHs were those events that were adjudicated and confirmed as such by the CEAC. Frequency of CVH was calculated using negative binomial regression analysis with study intervention, study, geographic region, daratumumab usage at Baseline, and offset term equal to log of each participant's follow-up time for cardiovascular hospitalization included in the model.

Change in heart function was measured by GLS%, a noninvasive imaging technique that uses echocardiography to assess heart. GLS% expresses longitudinal shortening as a percentage (change in length as a proportion to baseline length) and is reported as a negative value. A more negative value is usually associated with cardiac enhancement.

The SF-36v2 is a self-administered questionnaire containing 36 items that measure health on functional status, well-being, and overall evaluation of health in 8 domains, including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health, using scaled, ordinal responses (for example, All of the time, Most of the time, A good bit of the time). The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, with higher scores indicating an increased quality of life. The 8 multi-item scales are aggregated and summed to give the final PCS. The final score ranges from 0-100, with higher scores indicating an increased quality of life.

For each participant, blood samples were assayed for NT-proBNP, comparing the participant's baseline value over time to assess reduced amyloidosis, as measured by a decrease in NT-proBNP. A decrease indicates cardiac enhancement. Results reported as nanograms/milliliter (ng/mL).