{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:55:52Z","timestamp":1791320152142,"version":"4.3.1"},"reference-count":26,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2020,8,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Crenezumab is a fully humanized, monoclonal anti-amyloid-\u03b2 immunoglobulin G4 antibody.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This Phase Ib study (NCT02353598) evaluated the safety, tolerability, and pharmacokinetics of crenezumabat doses of \u2264120\u200amg\/kg administered intravenously every 4 weeks (q4w). Immunogenicity and exploratory biomarkers were also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In this multicenter, double-blind study, participants (aged 50\u201390 years) with mild-to-moderate Alzheimer\u2019s disease (AD) and amyloid-positive positron emission tomography (PET) scan were randomized to receive crenezumab 30 or 45\u200amg\/kg (Cohort 1, n\u200a=\u200a21), 60\u200amg\/kg (Cohort 2, n\u200a=\u200a21), or 120\u200amg\/kg (Cohort 3, n\u200a=\u200a19) or corresponding placebo ( n\u200a=\u200a14) intravenously q4w for 13 weeks. Seventy-one participants were subsequently enrolled in an optional open-label extension (OLE) and received crenezumab at the originally assigned dose level, except for Cohort 3 (crenezumab 60\u200amg\/kg during OLE). Participants received regular brain MRIs to assess amyloid-related imaging abnormalities (ARIA). Results up to Week 133 are reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Approximately 94% of participants experienced \u22651 adverse event (AE). Most AEs were mild or moderate; 15.5% experienced a Grade \u22653 AE. No ARIA-edema\/effusion (ARIA-E) events were observed. New ARIA-micro hemorrhages and hemosiderosis (ARIA-H) were reported in 4.9% (double-blind treatment period) and 9.9% (combined double-blind treatment and OLE periods) of participants. Steady-state trough concentrations of crenezumab were dose-proportional and maintained for each dose level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Crenezumab doses of \u2264120\u200amg\/kg intravenously q4w were well tolerated. The observed safety profile for \u2264133 weeks of treatment in a mild-to-moderate AD population was similar to that seen in previous trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-200134","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T12:09:43Z","timestamp":1592568583000},"page":"967-979","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":62,"title":["Safety, Tolerability, and Pharmacokinetics of Crenezumab in Patients with Mild-to-Moderate Alzheimer\u2019s Disease Treated with Escalating Doses for up to 133\u00a0Weeks"],"prefix":"10.1177","volume":"76","author":[{"given":"Heather","family":"Guthrie","sequence":"first","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence S.","family":"Honig","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Lin","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaycee M.","family":"Sink","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Blondeau","sequence":"additional","affiliation":[{"name":"F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Quartino","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dolton","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Carrasco-Triguero","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinshu","family":"Lian","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bittner","sequence":"additional","affiliation":[{"name":"F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Clayton","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Smith","sequence":"additional","affiliation":[{"name":"F. Hoffmann-La Roche Ltd, Welwyn Garden City, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Ostrowitzki","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,6,17]]},"reference":[{"key":"ref001","unstructured":"PrinceM, Comas-HerreraA, KnappM, GuerchetM, KaragiannidouM (2016)\n                      World Alzheimer Report 2016. Improving healthcare for peopleliving with dementia coverage: Quality and costs now and in the future\n                      . Alzheimer\u2019s Disease International, London, UK."},{"key":"ref002","unstructured":"Alzheimer\u2019s Association, What is Alzheimer\u2019s? Alzheimer\u2019s and Dementia basics, https:\/\/www.alz.org\/alzheimers-dementia\/what-is-alzheimers"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.56"},{"key":"ref004","first-page":"205","volume":"1","author":"Cummings J","year":"2012","journal-title":"Am J Neurodegener Dis"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3586"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070055"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811698106"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq056"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2583"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006338"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12191"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4742-11.2012"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1038\/srep39374"},{"key":"ref015","first-page":"P1669","volume":"14","author":"Yang T","year":"2018","journal-title":"Alzheimers Dement"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0553-5"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005550"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-018-0424-5"},{"key":"ref019","unstructured":"ClinicalTrials.gov, CREAD Study: A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer\u2019s Disease (AD). ClinicalTrials.gov Identifier: NCT02670083, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02670083."},{"key":"ref020","unstructured":"ClinicalTrials.gov, A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer\u2019s Disease (AD) (CREAD 2). ClinicalTrials.gov Identifier: NCT03114657, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03114657"},{"key":"ref021","first-page":"150","volume":"4","author":"Tariot PN","year":"2018","journal-title":"Alzheimers Dement"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3475"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-0580-2"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.90.15_supplement.P6.182"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.88.16_supplement.S7.005"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2016.10.015"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-200134","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-200134","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-200134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:08:25Z","timestamp":1777370905000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-200134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,17]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,8,4]]}},"alternative-id":["10.3233\/JAD-200134"],"URL":"https:\/\/doi.org\/10.3233\/jad-200134","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,17]]}}}