Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Japanese participant data from three gantenerumab trials in early Alzheimer's disease.
СтатьяРандомизированное исследованиеКлиническое исследование II фазыКлиническое исследование III фазыНазвание и аннотация: Перевод пока не подготовлен
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Asada Takashi, Thanasopoulou Angeliki, Delmar Paul, Wojtowicz Jakub, Smith Janice, Yoshiyama Yasumasa, Yokoi Katsunori, Watanabe Chigusa, Isozaki Mitsuhiro, Ozaki Ryoto, Ishida Takaaki, Tatsuda Hironori, Tamaoka Akira
Аннотация
INTRODUCTION: Gantenerumab was investigated in Japanese participants with mild cognitive impairment due to Alzheimer's disease (AD) or mild AD in two global phase 3 trials (GRADUATE I/II), and a phase 2 trial in Japan (JP40959).
METHODS: Of 1965 participants randomized in GRADUATE I/II (global-GRADUATE), 132 participants were enrolled from Japan (Japanese-GRADUATE) and 67 Japanese participants were randomized 2:1:1 to high-, low-dose gantenerumab, and placebo in JP40959.
RESULTS: Slowing of cognitive and functional decline, and amyloid reduction in gantenerumab group compared to placebo group were greater in Japanese-GRADUATE than in the global-GRADUATE and JP40959. Plasma gantenerumab concentrations in the Japanese-GRADUATE were slightly higher than in the global-GRADUATE and comparable to JP40959. Gantenerumab was well tolerated in the Japanese-GRADUATE and JP40959, matching the safety profile of the global-GRADUATE.
DISCUSSION: Differences in results across the populations studied could be related to imbalances in baseline body weight, amyloid load, and disease severity.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT03444870, NCT03443973; Japan Registry for Clinical Trials ID: jRCT2080224569.
HIGHLIGHTS: Gantenerumab was evaluated in Japanese participants with Alzheimer's disease (AD) in two global phase 3 trials and a phase 2 trial in Japan. Relative reduction in Clinical Dementia Rating Sum of Boxes (CDR-SB) deterioration favored gantenerumab in Japanese-GRADUATE (42%) more than in global-GRADUATE (9%) and JP40959 (-24%). Amyloid reduction in Japanese-GRADUATE was greater than in global-GRADUATE and JP40959. Overall, 72.7% and 27.5% of Japanese- and global-GRADUATE, respectively, achieved an amyloid-negative status. Cognitive and functional decline, and amyloid reduction could be related to baseline body weight and disease severity.
METHODS: Of 1965 participants randomized in GRADUATE I/II (global-GRADUATE), 132 participants were enrolled from Japan (Japanese-GRADUATE) and 67 Japanese participants were randomized 2:1:1 to high-, low-dose gantenerumab, and placebo in JP40959.
RESULTS: Slowing of cognitive and functional decline, and amyloid reduction in gantenerumab group compared to placebo group were greater in Japanese-GRADUATE than in the global-GRADUATE and JP40959. Plasma gantenerumab concentrations in the Japanese-GRADUATE were slightly higher than in the global-GRADUATE and comparable to JP40959. Gantenerumab was well tolerated in the Japanese-GRADUATE and JP40959, matching the safety profile of the global-GRADUATE.
DISCUSSION: Differences in results across the populations studied could be related to imbalances in baseline body weight, amyloid load, and disease severity.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT03444870, NCT03443973; Japan Registry for Clinical Trials ID: jRCT2080224569.
HIGHLIGHTS: Gantenerumab was evaluated in Japanese participants with Alzheimer's disease (AD) in two global phase 3 trials and a phase 2 trial in Japan. Relative reduction in Clinical Dementia Rating Sum of Boxes (CDR-SB) deterioration favored gantenerumab in Japanese-GRADUATE (42%) more than in global-GRADUATE (9%) and JP40959 (-24%). Amyloid reduction in Japanese-GRADUATE was greater than in global-GRADUATE and JP40959. Overall, 72.7% and 27.5% of Japanese- and global-GRADUATE, respectively, achieved an amyloid-negative status. Cognitive and functional decline, and amyloid reduction could be related to baseline body weight and disease severity.