| Title: |
Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial |
| Authors: |
Bateman, RJ; Li, Y; McDade, EM; Llibre-Guerra, JJ; Clifford, DB; Atri, A; Mills, SL; Santacruz, AM; Wang, G; Supnet, C; Benzinger, TLS; Gordon, BA; Ibanez, L; Klein, G; Baudler, M; Doody, RS; Delmar, P; Kerchner, GA; Bittner, T; Wojtowicz, J; Bonni, A; Fontoura, P; Hofmann, C; Kulic, L; Hassenstab, J; Aschenbrenner, AJ; Perrin, RJ; Cruchaga, C; Renton, AE; Xiong, C; Goate, AA; Morris, JC; Holtzman, DM; Snider, BJ; Mummery, C; Brooks, WS; Wallon, D; Berman, SB; Roberson, E; Masters, CL; Galasko, DR; Jayadev, S; Sanchez-Valle, R; Pariente, J; Kinsella, J; van Dyck, CH; Gauthier, S; Hsiung, GYR; Masellis, M; Dubois, B; Honig, LS; Jack, CR; Daniels, A; Aguillón, D; Allegri, R; Chhatwal, J; Day, G; Fox, NC; Huey, E; Ikeuchi, T; Jucker, M; Lee, JH; Levey, AI; Levin, J; Lopera, F; Roh, JH; Rosa-Neto, P; Schofield, PR |
| Source: |
The Lancet Neurology , 24 (4) pp. 316-330. (2025) |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2025 |
| Collection: |
University College London: UCL Discovery |
| Description: |
BACKGROUND: Amyloid plaque removal by monoclonal antibody therapies slows clinical progression in symptomatic Alzheimer's disease; however, the potential for delaying the onset of clinical symptoms in asymptomatic people is unknown. The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) is an ongoing platform trial assessing the safety and efficacy of multiple investigational products in participants with dominantly inherited Alzheimer's disease (DIAD). Based on findings of amyloid removal and downstream biological effects from the gantenerumab group of the platform trial, we continued a 3-year open-label extension (OLE) study to assess the safety and efficacy of long-term treatment with high doses of gantenerumab. METHODS: The randomised, placebo-controlled, double-blind, phase 2/3 multi-arm trial (DIAN-TU-001) assessed solanezumab or gantenerumab versus placebo in participants who were between 15 years before and 10 years after their estimated years to symptom onset and who had a Clinical Dementia Rating (CDR) global score of 0 (cognitively normal) to 1 (mild dementia). This study was followed by an OLE study of gantenerumab treatment, conducted at 18 study sites in Australia, Canada, France, Ireland, Puerto Rico, Spain, the UK, and the USA. For inclusion in the OLE, participants at risk for DIAD had participated in the double-blind period of DIAN-TU-001 and were required to know their mutation status. We investigated increasing doses of subcutaneous gantenerumab up to 1500 mg every 2 weeks. Due to the lack of a regulatory path for gantenerumab, the study was stopped early after a prespecified interim analysis (when most participants had completed 2 years of treatment) of the clinical measure CDR-Sum of Boxes (CDR-SB). The primary outcome for the final analysis was the amyloid plaque measure 11C-Pittsburgh compound-B positron emission tomography (PiB-PET) standardised uptake value ratio (SUVR [PiB-PET SUVR]) at 3 years, assessed in the modified intention-to-treat group (mITT; defined as participants ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10208456/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10208456/1/Accepted%20version%20Safety%20and%20efficacy%20of%20long-term%20gantenerumab%20treatment%20in%20dominantly%20inherited%20Alzheimer%27s.pdf; https://discovery.ucl.ac.uk/id/eprint/10208456/ |
| Rights: |
open |
| Accession Number: |
edsbas.45BCC7E3 |
| Database: |
BASE |