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O1‐09‐06: 24‐MONTH ANALYSIS OF CHANGE FROM BASELINE IN CLINICAL DEMENTIA RATING SCALE COGNITIVE AND FUNCTIONAL DOMAINS IN PRIME: A RANDOMIZED PHASE 1B STUDY OF THE ANTI–AMYLOID BETA MONOCLONAL ANTIBODY ADUCANUMAB
Author(s) -
Haeberlein Samantha Budd,
Castrillo-Viguera Carmen,
Gheuens Sarah,
Chen Tianle,
O'Gorman John,
Chiao Ping,
Wang Guanfang,
Hehn Christian,
Skordos LeAnne,
Hock Christoph,
Nitsch Roger M.,
Rosenstiel Philip,
Sandrock Alfred
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2383
Subject(s) - placebo , medicine , randomized controlled trial , population , clinical endpoint , clinical dementia rating , dementia , cohort , disease , pathology , alternative medicine , environmental health
blind dose. Target dose and titration schemes were modelled based on all available data with mAb targeting aggregated amyloid, to achieve maximum amyloid reduction while maintaining safety and tolerability. Protocol measures included MRI monitoring and dosing algorithm. Results:As of January 16, 2018, OLE duration ranged 12–101 weeks (median: 63.9 weeks). 103/154 patients received 1200mg gantenerumab for 1–81 weeks. ARIAs were detected in 47/133 patients with a post-baseline MRI; 38 patients had ARIA-E, 61% of whom had ARIA-H. ARIA-E incidence increased with dose (Table), with overall rate 28.6%. Most ARIAs (84%) were asymptomatic and non-serious. Incidence (79%) and severity of adverse events (including ISRs) remained comparable to SCarlet RoAD low-dose double-blind treatment. Conclusions: This updated Scarlet RoAD OLE safety analysis showed no new or unexpected findings with longer exposure to high-dose gantenerumab. ARIA-E rate increased with dose, but the titration appeared to reduce ARIA-E risk with overall incidence <30%. ARIAs appeared manageable with implemented protocol measures. These data support the use of titration to high-dose gantenerumab in the phase 3 GRADUATE program. 1. Andjelkovic, CTAD 2017.