{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:33:28Z","timestamp":1793298808876,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T00:00:00Z","timestamp":1552867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Cerebral amyloid angiopathy (\n                      <jats:styled-content style=\"fixed-case\">CAA<\/jats:styled-content>\n                      ) is caused by cerebrovascular deposition of\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010amyloid fragments leading to cerebrovascular dysfunction and other brain injuries. This phase 2, randomized, double\u2013blind trial in patients with probable\n                      <jats:styled-content style=\"fixed-case\">CAA<\/jats:styled-content>\n                      assessed the efficacy and safety of ponezumab, a novel monoclonal antibody against A\n                      <jats:italic>\u03b2<\/jats:italic>\n                      <jats:sub>1\u201340<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Thirty\u2010six participants aged 55\u201380\u00a0years with probable\n                      <jats:styled-content style=\"fixed-case\">CAA<\/jats:styled-content>\n                      received intravenous placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a012) or ponezumab (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a024). The change from baseline to Days 2 and 90 in cerebrovascular reactivity (\n                      <jats:styled-content style=\"fixed-case\">CVR<\/jats:styled-content>\n                      ) was measured in the visual cortex as the natural log of the rising slope of the\n                      <jats:styled-content style=\"fixed-case\">BOLD fMRI<\/jats:styled-content>\n                      response to a visual stimulus. Safety and tolerability were also assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The mean change from baseline to Day 90 was 0.817 (ponezumab) and 0.958 (placebo): a mean ratio of 0.852 (90%\n                      <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\n                      0.735\u20130.989) representing a trend towards\n                      <jats:italic>reduced<\/jats:italic>\n                      <jats:styled-content style=\"fixed-case\">CVR<\/jats:styled-content>\n                      in the ponezumab group. This trend was not present at Day 2. There was one asymptomatic occurrence of amyloid\u2013related imaging abnormality\u2013edema 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Ponezumab was safe and well\u2010tolerated. The ponezumab group showed a trend towards treatment effect at Day 90 that was opposite to the hypothesized direction. The prespecified efficacy criteria were thus not met.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.761","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T11:44:33Z","timestamp":1552909473000},"page":"795-806","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Immunotherapy with ponezumab for probable cerebral amyloid angiopathy"],"prefix":"10.1002","volume":"6","author":[{"given":"Claire","family":"Leurent","sequence":"first","affiliation":[{"name":"Pfizer Worldwide Research &amp; Development Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research &amp; Development Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pfizer 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