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Here, we report the results of TANGO (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03352557\">NCT03352557<\/jats:ext-link>\n                    ), a randomized, double-blind, placebo-controlled, parallel-group and multiple-dose long-term trial of gosuranemab\u2014a monoclonal antibody to N-terminal tau\u2014in patients with early Alzheimer\u2019s disease. The primary objective was to assess the safety and tolerability of gosuranemab compared to placebo. The secondary objectives were to assess the efficacy of multiple doses of gosuranemab in slowing cognitive and functional impairment (using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores at week 78) and evaluate the immunogenicity of gosuranemab (using the incidence of anti-gosuranemab antibody responses). Participants were randomized (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009654); received (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009650) low-dose (125\u2009mg once every 4 weeks (q4w),\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200958; 375\u2009mg q12w,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200958), intermediate-dose (600\u2009mg q4w,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009106) or high-dose (2,000\u2009mg q4w,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009214) gosuranemab or placebo (q4w,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009214) intravenously for 78 weeks; and assigned to cerebrospinal fluid (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009327) and\/or tau positron emission tomography (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009357) biomarker substudies. Gosuranemab had an acceptable safety profile and was generally well tolerated (incidence of serious adverse events: placebo, 12.1%; low dose, 10.3%; intermediate dose, 12.3%; high dose, 11.7%). The incidence of treatment-emergent gosuranemab antibody responses was low at all time points. No significant effects were identified in cognitive and functional tests as no dose resulted in a favorable change from the baseline CDR-SB score at week 78 compared to placebo control (adjusted mean change: placebo, 1.85; low dose, 2.20; intermediate dose, 2.24; high dose, 1.85). At week 76, all doses caused significant (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001) reductions in the cerebrospinal fluid levels of unbound N-terminal tau compared to placebo.\n                  <\/jats:p>","DOI":"10.1038\/s43587-023-00523-w","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T12:04:46Z","timestamp":1701086686000},"page":"1591-1601","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["TANGO: a placebo-controlled randomized phase 2 study of efficacy and safety of the anti-tau monoclonal antibody gosuranemab in early Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5550-9077","authenticated-orcid":false,"given":"Melanie","family":"Shulman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"O\u2019Gorman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ratti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajasimhan","family":"Rajagovindan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Viollet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie M.","family":"Racine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Czerkowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Hering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4824-646X","authenticated-orcid":false,"given":"Samantha Budd","family":"Haeberlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"523_CR1","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","volume":"179","author":"JM Long","year":"2019","unstructured":"Long, J. 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