Efficacy and safety of GV1001 in patients with moderate-to-severe Alzheimer’s disease already receiving donepezil: a phase 2 randomized, double-blind, placebo-controlled, multicenter clinical trial

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.

Beyond lecanemab: Examining Phase III potential in Alzheimer's therapeutics

“…Participants received either 0.56 or 1.12 mg of the drug weekly for 4 weeks, followed by 10 injections every 2 weeks until Week 24. The findings indicated good tolerability, with statistical significance in efficacy observed only with the higher concentration (1.12 mg) as measured by the Clinical Dementia Rating Box‐Summary (CDR‐SB) and Alzheimer's Disease Cooperative Study‐Activities of Daily Living (ADCS‐ADL) 21 . Common adverse effects included nasopharyngitis, diarrhea, anxiety, back pain, arthralgia, and loss of appetite, occurring at an incidence rate of less than 10% 21 …”

“…The findings indicated good tolerability, with statistical significance in efficacy observed only with the higher concentration (1.12 mg) as measured by the Clinical Dementia Rating Box-Summary (CDR-SB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). 21 Common adverse effects included nasopharyngitis, diarrhea, anxiety, back pain, arthralgia, and loss of appetite, occurring at an incidence rate of less than 10%. 21 In Korea, an endorsed Phase III clinical trial for AD has been initiated, 22 while a Phase II clinical trial for AD has commenced in the United States.…”

“…21 Common adverse effects included nasopharyngitis, diarrhea, anxiety, back pain, arthralgia, and loss of appetite, occurring at an incidence rate of less than 10%. 21 In Korea, an endorsed Phase III clinical trial for AD has been initiated, 22 while a Phase II clinical trial for AD has commenced in the United States. 22 Fosgonimeton (ATH-1017) Fosgonimeton (ATH-1017) is a small compound developed to enhance the activity of hepatocyte growth factor (HGF) and its receptor, mesenchymal-epithelial transition factor (MET).…”

Tangeretin Inhibits BACE1 Activity and Attenuates Cognitive Impairments in AD Model Mice

“…4 Drugs targeting cholinergic and N-methyl-D-aspartic acid (NMDA) receptors have been used clinically to improve AD symptoms, although their neuroprotective activity remains debatable. 5,6 Therefore, disease-modifying pharmaceutical therapeutic strategies are warranted to prevent or slow the course of AD, especially focusing on the reduction of Aβ production. 1,2,7,8 β-secretase (BACE1) is essential for the generation of all monomeric forms of Aβ.…”

“…In 2018, Alzheimer’s Disease International estimated that approximately 50 million AD patients exist worldwide, and the prevalence of AD may triple by 2050 . Drugs targeting cholinergic and N -methyl- d -aspartic acid (NMDA) receptors have been used clinically to improve AD symptoms, although their neuroprotective activity remains debatable. , Therefore, disease-modifying pharmaceutical therapeutic strategies are warranted to prevent or slow the course of AD, especially focusing on the reduction of Aβ production. ,,, …”