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Immunotherapy with ponezumab for probable cerebral amyloid angiopathy

Leurent, C; Goodman, JA; Zhang, Y; He, P; Polimeni, JR; Gurol, ME; Lindsay, M; ... Savitz, SI; + view all (2019) Immunotherapy with ponezumab for probable cerebral amyloid angiopathy. Annals of Clinical and Translational Neurology , 6 (4) pp. 795-806. 10.1002/acn3.761. Green open access

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Abstract

Objective: Cerebral amyloid angiopathy (CAA) is caused by cerebrovascular deposition of β‐amyloid fragments leading to cerebrovascular dysfunction and other brain injuries. This phase 2, randomized, double–blind trial in patients with probable CAA assessed the efficacy and safety of ponezumab, a novel monoclonal antibody against Aβ1–40. Methods: Thirty‐six participants aged 55–80 years with probable CAA received intravenous placebo (n = 12) or ponezumab (n = 24). The change from baseline to Days 2 and 90 in cerebrovascular reactivity (CVR) was measured in the visual cortex as the natural log of the rising slope of the BOLD fMRI response to a visual stimulus. Safety and tolerability were also assessed. Results: The mean change from baseline to Day 90 was 0.817 (ponezumab) and 0.958 (placebo): a mean ratio of 0.852 (90% CI 0.735–0.989) representing a trend towards reduced CVR in the ponezumab group. This trend was not present at Day 2. There was one asymptomatic occurrence of amyloid–related imaging abnormality–edema in the ponezumab group. The total number of new cerebral microbleeds from baseline to day 90 did not differ between groups. The ponezumab group had a participant with nonfatal new cerebral hemorrhage with aphasia and a participant with subdural hemorrhage that site investigators deemed to be nondrug related. In the placebo group one participant had a fatal intracerebral hemorrhage and one participant had migraine with aura.

Type: Article
Title: Immunotherapy with ponezumab for probable cerebral amyloid angiopathy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/acn3.761
Publisher version: https://doi.org/10.1002/acn3.761
Language: English
Additional information: © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/10075305
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