INmune Bio Inc. has announced results from an additional blinded interim analysis of its AD02 Phase II Alzheimer's Disease (AD) trial, demonstrating a significant correlation between the novel cognitive measure EMACC (Early AD/MCI Alzheimer’s Cognitive Composite) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB). The analysis, conducted independently, showed a highly significant correlation (p<0.001) between baseline EMACC scores and CDR-SB, the accepted endpoint for AD trials.
The Early AD/ MCI Alzheimer’s Cognitive Composite (EMACC) is an empirically derived cognitive measure composed of standardized and widely used neuropsychological tests. These tests, in combination, showed the greatest sensitivity to change in Early Alzheimer’s Disease (AD) patients over two years of follow-up. The performance characteristics of EMACC in early AD were first reported by Biogen at CTAD in 2021. Notably, EMACC was also found to be strongly associated with biological markers of inflammation in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) AD study.
EMACC Performance and Reliability
The analysis also highlighted the reliability of EMACC, with a correlation of 0.93 observed when measured during the screening process and at the first study visit before treatment. This high degree of precision suggests that EMACC can produce robust and replicable results even with smaller sample sizes. Furthermore, EMACC demonstrated a strong ability to differentiate between patients with CDR global ratings of 0.5 (prodromal AD) and those with ratings of 1.0 (mild dementia), with an effect size (Cohen’s d) of 0.87 (p<.0001).
Expert Commentary
Judith Jaeger, Ph.D., the principal developer of EMACC, stated, "Based on how the EMACC was developed, we expected a robust correlation between EMACC and CDR when used side-by-side in a clinical trial, and this analysis, while confirming our hypothesis, also validates the selection of the cognitive endpoints measured in the AD02 trial. The CDR-SB was not designed to measure cognitive change in clinical trials; it was developed as a staging instrument and relies largely on subjective assessments. The EMACC, on the other hand, was empirically derived to measure cognitive change in early AD patients objectively. This high degree of precision offers a more accurate assessment of cognitive function."
Trial Design and Future Outlook
C.J. Barnum, Ph.D., VP of Neuroscience at INmune Bio, commented on the trial design, stating, "We believe the novel design elements used in our AD02 Phase 2 trial significantly de-risk our clinical program compared to traditional trial designs in AD drug development, and this analysis overwhelmingly supports our decision to use EMACC as the primary endpoint while further validating both size and duration of the trial." The company anticipates completing enrollment near the end of the current quarter and expects to announce topline data approximately six months after the last patient is enrolled.
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