2023 American Academy of Neurology Abstract Website

Sheila Seleri¹, Sharon Brangman², J. Neil Henderson³, Monica Parker⁴, Stephanie Monroe⁵, Jacobo Mintzer⁶, Alexandria Wise-Brown¹, Michael Grundman⁷, Janice Smith⁸, Rachelle Doody⁸, Helen Lin¹, Beverly Assman¹, Gregory Rippon¹
¹Genentech, Inc., a member of the Roche Group, ²SUNY Upstate Medical University, ³University of Minnesota, ⁴Goizueta Alzheimer’s Disease Research Center, Emory University School of Medicine, ⁵UsAgainstAlzheimer's, ⁶Medical University of South Carolina, ⁷Global R&D Partners, LLC, ⁸F. Hoffmann-La Roche Ltd.

Objective:

We aim to evaluate efficacy, safety, and pharmacokinetics/pharmacodynamics of gantenerumab in amyloid-positive participants with early symptomatic Alzheimer’s disease ([AD]; ie, mild cognitive impairment [MCI] due to AD or mild AD dementia) in historically underrepresented populations. Gantenerumab is a fully human anti-amyloid antibody currently being evaluated in two phase III trials (GRADUATE I and II).

Background:

Historic underrepresentation of many racial/ethnic groups in AD clinical trials limits our understanding of AD and hinders data generalizability.

Design/Methods:

ALUMNI AD, a Phase IIIb, multisite, single-arm, open-label US-based study, will evaluate gantenerumab over a 2-year treatment period and 2-year extension. Sites will be distributed across the US based on local AD prevalence and racial/ethnic demographics, and providers’ experience/engagement providing care in diverse communities. Key eligibility criteria include self-reported race/ethnicity as Black/African American, Hispanic/Latinx, American Indian/Alaska Native, Asian American, or Native Hawaiian or Other Pacific Islander; early symptomatic AD diagnosis; age 50-90 years; evidence of amyloid-beta pathology (measured by amyloid positron emission tomography [PET]); and a reliable study partner/partners. Eligibility assessments include the Quick Dementia Rating System and Mini Mental State Examination. The primary endpoint is change from baseline to Week 104 in brain amyloid load (PET). Secondary and exploratory endpoints include changes in additional AD biomarkers (eg, tau), safety assessments, and cognitive and functional outcomes.

Results:

Planned enrollment is approximately 200 participants from up to 40 US sites. The study is expected to start in the first quarter of 2023 pending supportive data from the GRADUATE program, which will be available in the fourth quarter of 2022.

Conclusions:

This study will further our understanding of gantenerumab in historically underrepresented populations who are disproportionately impacted by AD and have been historically excluded from clinical trials.