Seong-Ho Koh1,2, Hyuk Sung Kwon3, Seong Hye Choi4, Jee Hyang Jeong5, Hae Ri Na6, Chan Nyoung Lee7, YoungSoon Yang8, Ae Young Lee9, Jae-Hong Lee10, Kyung Won Park11, Hyun Jeong Han12, Byeong C Kim13, Jin Se Park14, Jee-Young Lee15, Sangjae Kim16, Kyu-Yong Lee3. 1. Department of Neurology, Hanyang University Guri Hospital, Hanyang University College of Medicine, 153, Gyeongchun-ro, Guri, 11923, South Korea. ksh213@hanyang.ac.kr. 2. Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering, Seoul, 04763, South Korea. ksh213@hanyang.ac.kr. 3. Department of Neurology, Hanyang University Guri Hospital, Hanyang University College of Medicine, 153, Gyeongchun-ro, Guri, 11923, South Korea. 4. Department of Neurology, Inha University School of Medicine, Incheon, 22332, South Korea. 5. Department of Neurology, Ewha Womans University School of Medicine, Seoul, 07985, South Korea. 6. Department of Neurology, Bobath Memorial Hospital, Seongnam, 13552, South Korea. 7. Department of Neurology, Korea University Anam Hospital, Seoul, 02856, South Korea. 8. Department of Neurology, Veterans Health Service Medical Center, Seoul, 05368, South Korea. 9. Department of Neurology, Chungnam National University Hospital, Daejeon, 35015, South Korea. 10. Department of Neurology, Asan Medical Center, Seoul, 05505, South Korea. 11. Department of Neurology, Dong-A University Hospital, Busan, 49201, South Korea. 12. Department of Neurology, Myongji Hospital, Hanyang University College of Medicine, Goyang, 10475, South Korea. 13. Department of Neurology, Chonnam National University Hospital, Gwangju, 61469, South Korea. 14. Department of Neurology, Inje University Haeundae Paik Hospital, Buasn, 48108, South Korea. 15. Department of Neurology, Seoul National University Boramae Medical Center, Seoul, 07061, South Korea. 16. Teloid Inc., 920 Westholme Ave, Los Angeles, CA, 90024, USA.
Abstract
BACKGROUND: Our previous studies showed that GV1001 has various protective effects against β-amyloid and other stressors. Based on these findings, we hypothesized that GV1001 might have beneficial effects in patients with Alzheimer's disease (AD). METHODS: A phase 2, double-blind, parallel-group, placebo-controlled, 6-month randomized clinical trial was performed to evaluate the safety and efficacy of subcutaneously administered GV1001. Between September 2017 and September 2019, 13 centers in South Korea recruited participants. A total of 106 patients were screened, and 96 patients with moderate-to-severe AD were randomized 1:1:1 to the placebo (group 1, n = 31), GV1001 0.56 mg (group 2, n = 33), and 1.12 mg (group 3, n = 32) groups. GV1001 was administered every week for 4 weeks (4 times), followed by every 2 weeks until week 24 (10 times). The primary endpoint was the change in the Severe Impairment Battery (SIB) score from baseline to week 24. The key secondary efficacy endpoints were the change in the Clinical Dementia Rating Sum of Box (CDR-SOB), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination, and Global Deterioration Scale scores. The safety endpoints were also assessed based on adverse events, laboratory test results, vital signs, and other observations related to safety. RESULTS: Group 3 showed less decrease in the SIB score at 12 and 24 weeks compared with group 1 (P < 0.05). These were not significantly observed in group 2. Among the secondary endpoints, only the NPI score showed significantly better improvement in group 2 than in group 3 at week 12; however, there were no other significant differences between the groups. Although the ADCS-ADL and CDR-SOB scores showed a pattern similar to SIB scores, a statistically significant result was not found. Adverse events were similar across all three groups. CONCLUSIONS: The results indicate that GV1001 1.12 mg met the primary endpoint of a statistically significant difference. GV1001 was well tolerated without safety concerns. This study warrants a larger clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03184467 . Registered on June 12, 2017.
RCT Entities:
BACKGROUND: Our previous studies showed that GV1001 has various protective effects against β-amyloid and other stressors. Based on these findings, we hypothesized that GV1001 might have beneficial effects in patients with Alzheimer's disease (AD). METHODS: A phase 2, double-blind, parallel-group, placebo-controlled, 6-month randomized clinical trial was performed to evaluate the safety and efficacy of subcutaneously administered GV1001. Between September 2017 and September 2019, 13 centers in South Korea recruited participants. A total of 106 patients were screened, and 96 patients with moderate-to-severe AD were randomized 1:1:1 to the placebo (group 1, n = 31), GV1001 0.56 mg (group 2, n = 33), and 1.12 mg (group 3, n = 32) groups. GV1001 was administered every week for 4 weeks (4 times), followed by every 2 weeks until week 24 (10 times). The primary endpoint was the change in the Severe Impairment Battery (SIB) score from baseline to week 24. The key secondary efficacy endpoints were the change in the Clinical Dementia Rating Sum of Box (CDR-SOB), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination, and Global Deterioration Scale scores. The safety endpoints were also assessed based on adverse events, laboratory test results, vital signs, and other observations related to safety. RESULTS: Group 3 showed less decrease in the SIB score at 12 and 24 weeks compared with group 1 (P < 0.05). These were not significantly observed in group 2. Among the secondary endpoints, only the NPI score showed significantly better improvement in group 2 than in group 3 at week 12; however, there were no other significant differences between the groups. Although the ADCS-ADL and CDR-SOB scores showed a pattern similar to SIB scores, a statistically significant result was not found. Adverse events were similar across all three groups. CONCLUSIONS: The results indicate that GV1001 1.12 mg met the primary endpoint of a statistically significant difference. GV1001 was well tolerated without safety concerns. This study warrants a larger clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03184467 . Registered on June 12, 2017.
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