Abstract

BackgroundOur 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).MethodsA 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.ResultsGroup 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.ConclusionsThe 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 registrationClinicalTrials.gov NCT03184467. Registered on June 12, 2017.

Highlights

  • Our previous studies showed that GV1001 has various protective effects against β-amyloid and other stressors

  • Significant differences in baseline characteristics, including age, sex, and age at Alzheimer’s disease (AD) diagnosis, years since diagnosis, and K-Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Box (CDR-SOB), Neuropsychiatric Inventory (NPI), Global Deterioration Scale (GDS), ADCSADL, and Clinician Interview-based Impression of Severity scores were not observed between the three groups (Table 1 and Additional file 2, Table S3)

  • In this study, we demonstrated that GV1001 might have beneficial effects on the cognition and activities of daily living in patients with moderate-to-severe AD already receiving donepezil

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Summary

Introduction

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). The most important pathological findings of AD include senile plaques caused by βamyloid (Aβ) and neurofibrillary tangles due to hyperphosphorylated tau [3]. Neuroinflammation is another important pathological finding that accompanies AD [4]. A total of five drugs have been approved for the symptomatic treatment of AD, from tacrine in 1993 to memantine in 2003 They did not modify the pathologic progression, and tacrine treatment was discontinued in 2013 because of its hepatotoxicity. There are huge unmet medical needs for AD worldwide

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