{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:23:41Z","timestamp":1789712621947,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>This proof\u2010of\u2010concept, dose\u2010finding phase IIb trial evaluated treatment with ABBV\u2010552 compared with placebo in participants with clinically diagnosed mild Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Participants aged 50 to 90 years with a Mini\u2010Mental State Examination score of 20 to 26 and a global Clinical Dementia Rating score of 0.5 to 1.0 were randomized 1:1:1:1 to placebo or ABBV\u2010552 (1, 5, or 15\u00a0mg) daily. The primary endpoint was the change from baseline in the 14\u2010item Alzheimer's Disease Assessment Scale\u2010Cognitive Subscale (ADAS\u2010Cog 14) at week 12.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Two hundred sixty\u2010three participants were randomized. The least\u2010squares mean difference (vs placebo) in change from baseline at week 12 in ADAS\u2010Cog 14 total score (95% confidence interval) for ABBV\u2010552 1\u00a0mg was \u22120.02 (\u22121.87, 1.83), nominal\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.9819; 5\u00a0mg, \u22120.42 (\u22122.25, 1.42), nominal\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.6545; 15\u00a0mg, 0.25 (\u22121.58, 2.08), nominal\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.7860. Treatment\u2010emergent adverse events occurred in 48.5% of ABBV\u2010552 recipients versus 42.2% in the placebo group; no safety concerns were identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>ABBV\u2010552 did not demonstrate a meaningful difference versus placebo on the primary endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>ABBV\u2010552 is a small molecule that modulates the SV2A receptor in neurons<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>ABBV\u2010552 may enhance synaptic efficiency leading to improved cognition in patients with Alzheimer's disease (AD)<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Participants with mild AD were treated with either placebo, 1 mg, 5 mg, or 15 mg of ABBV\u2010552 covering an estimated 35% to 80% SV2A receptor occupancy in a phase II randomized clinical trial<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Results failed to show efficacy over placebo as measured by ADAS\u2010Cog 14 at week 12<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>ABBV\u2010552 was generally safe and well tolerated<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70994","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T11:55:17Z","timestamp":1766750117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ABBV\u2010552 in patients with mild Alzheimer's disease: a randomized phase IIb trial"],"prefix":"10.1002","volume":"21","author":[{"given":"Shau Yu","family":"Lynch","sequence":"first","affiliation":[{"name":"Clinical Development AbbVie Inc. North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Jia","sequence":"additional","affiliation":[{"name":"Statistics AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Miles","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey","family":"Boiser","sequence":"additional","affiliation":[{"name":"Pharmacovigilance and Patient Safety AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek L.","family":"Buhl","sequence":"additional","affiliation":[{"name":"Precision Medicine AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Graff","sequence":"additional","affiliation":[{"name":"Clinical Development AbbVie Inc. North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Zadikoff","sequence":"additional","affiliation":[{"name":"Clinical Development AbbVie Inc. North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"US Food and Drug Adminstration.FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia due to Alzheimer's Disease.2023.https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010approves\u2010first\u2010drug\u2010treat\u2010agitation\u2010symptoms\u2010associated\u2010dementia\u2010due\u2010alzheimers\u2010disease"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12516"},{"key":"e_1_2_10_4_1","unstructured":"World Health Organization.Dementia 2023. Accessed October 29 2024.https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010approves\u2010first\u2010drug\u2010treat\u2010agitation\u2010symptoms\u2010associated\u2010dementia\u2010due\u2010alzheimers\u2010disease"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2016.1216972"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1179573520907397"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa013128"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/s1092852915000954"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj\u20102021\u2010069780"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2022.02.456"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00557-x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.12548"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2023.2233892"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010020\u20100884\u20102"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.56105"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1066447"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010016\u20100384\u2010x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12097"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010023\u201002376\u20106"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.9.1021"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.318.7184.633"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000011554"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.09.010"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2015.06.001"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010016\u20100210\u20101"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.05.2091"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533558"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.13855"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13764"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543406.2013.834911"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad\u2010130575"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.937486"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2016.1258060"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.12.1852"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035\u2010022\u201000296\u2010z"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12017"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20225536"},{"key":"e_1_2_10_39_1","unstructured":"Immunoassay Blood Test for Amyloid Pathology Assessment. Accessed July 8 2025.https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfpmn\/pmn.cfm?ID=K242706"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70994","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70994","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T03:37:21Z","timestamp":1780285041000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/alz.70994"],"URL":"https:\/\/doi.org\/10.1002\/alz.70994","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70994"}}