CognitionMetrics, LLC and Albert Einstein College of Medicine
Psychiatry and Behavioral Sciences
Judith Jaeger is neuropsychologist and pharmaceutical executive with more than 30 years’ experience in clinical and experimental neuropsychology and psychopathology. She is Clinical Professor of Psychiatry and Behavioral Science at Albert Einstein College of Medicine, New York as well as President and Principal Scientist at CognitionMetrics, LLC in Wilmington, Delaware, USA. Previously she was Vice President for Clinical Trials at Cogstate, Inc. and Director of Clinical Development at AstraZeneca Pharmaceuticals where she served as company-wide cognition expert for programs in Alzheimer’s disease, ADHD, schizophrenia, bipolar disorder and oncology. Prof. Jaeger’s pharmaceutical industry work has included Phase 0 experimental medicine studies that she has initiated, as well as innovative (Phase Ib/IIa) and conventional (Phase II) PoP/PoC studies as well as pivotal (Phase III) and post-marketing studies. Her global regulatory experience includes speaking before regulatory bodies including the PMDA (Japanese regulatory authories) and with FDA including at an Advisory Committee. She has consulted to clinical teams in 15 of the top 25 pharmaceutical companies in all phases of development on a range of CNS and non-CNS (safety) indications. Professor Jaeger is known for her research on measurement of cognition across a range of central nervous system diseases, with particular attention to measurement of change over time in clinical trials. She has also studied cognitive impairments and their association with disability in psychiatric disorders, including schizophrenia, bipolar and major depressive disorder. She has over 70 peer-reviewed publications, one edited book, seven book chapters and more than 200 published abstracts, conference presentations and invited lectures.

Moderator of 1 Session

Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
05:15 PM - 07:45 PM
Room
ONSITE: 113

Presenter of 1 Presentation

ENDPOINT SELECTION AND POWER ESTIMATES FOR TH PRIMARY COGNITIVE ENDPOINT IN A PHASE 2 TRIAL OF XPRO1595 IN ALZHEIMER’S DISEASE (AD) WITH INFLAMMATION (ADI)

Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
05:15 PM - 07:45 PM
Room
ONSITE: 113
Lecture Time
05:30 PM - 05:45 PM

Abstract

Aims

An alternative cognitive endpoint is needed to the ADAS-Cog, which is almost uniformly used in clinical trials in Mild Alzheimer’s Disease (AD). This is despite extensive empirical evidence of ceiling effects on most items rendering them 1) insensitive to change in the mild stage of the disease and 2) inaccurate estimators of change magnitude since it is unknown how much change must occur to move the measure off the ceiling.

Methods

An alternative endpoint, the Early Mild Alzheimer’s Cognitive Composite (EMACC) was empirically developed in a four cohort collaboration (Jaeger, 2018) and includes 6 validated neuropsychological test paradigms that together demonstrate the steepest slope decline in amyloid confirmed Early/Mild AD. All these paradigms have reliably been used in global clinical trials.


The statistical power of EMACC was calculated in the ADNI cohort and compared with that of ADAS-Cog and CDR while planning a phase 2 trial of XPro1595, an immune modulator being tested in early Mild Alzheimer’s patients with inflammation (ADi).

Results

Mild ADi patients declined more during 12 months than the non-inflammed (ADAS-Cog 13 ES=0.46 vs 0.33; EMACC ES=0.76 vs 0.37). The N required to detect a clinically meaningful drug effect (80%power, 2-sided, Alpha=0.05) at 12 months in patients with ADi (given upper and lower ES assumptions) ranged from 130 to 188 for ADAS-Cog, 126 to 224 for CDR-SB and 56 to 86 for EMACC.

Conclusions

Inflammation accelerates AD cognitive decline. EMACC’s superior sensitivity to disease progression permits half the sample size to test the hypothesis of immune modulator XPro1595’s benefit to cognition.

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