A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Prospective, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Administration of GV1001 1.12 mg/Day in Patients With Moderate to Severe Alzheimer Disease
概览
- 阶段
- 3 期
- 干预措施
- GV1001 Placebo
- 疾病 / 适应症
- Moderate to Severe Alzheimer's Disease
- 发起方
- Samsung Pharmaceutical Co., Ltd.
- 入组人数
- 750
- 主要终点
- Change from baseline in SIB(Severe Impairment Battery) score after GV1001 administration for 24 weeks
- 状态
- 尚未招募
- 最后更新
- 2个月前
概览
简要总结
The objective of this study is to evaluate the safety and efficacy of GV1001 administered subcutaneously in patients with moderate to severe Alzheimer's disease (AD).
详细描述
Studies using in vivo and in vitro Alzheimer's Disease (AD) models have shown that GV1001 inhibits neurotoxicity, apoptosis, and the production of reactive oxygen species induced by amyloid beta (Aβ) in neural stem cells by mimicking the extra-telomeric functions of human telomerase reverse transcriptase (hTERT). In nonclinical studies, using both mild (early stage) and severe (late stage) AD mouse models, GV1001 was shown to improve cognitive function and memory, as well as significantly reduce the amount of Aβ and tau proteins. The multifunctional effect of GV1001 makes it a promising therapeutic option for the treatment for AD. In a completed Phase 2 study (NCT03184467) conducted in Korea, GV1001 showed significant improvement in change from baseline of Severe Impairment Battery score at Week 24 and demonstrated a clinically acceptable safety profile in patients with moderate to severe AD. This is a multi-center, randomized, double-blinded, placebo-controlled, parallel design, prospective phase 3 study in participants with moderate to severe AD. The study consists of 24 weeks of Double-blind phase and 25 weeks of open-label phase.
研究者
入排标准
入选标准
- •Subjects aged ≥ 55 to ≤ 85 years
- •Subjects who satisfy diagnostic criteria for dementia in DSM-IV (Diagnostic and Statistical Manual of Mental Disorders Fourth edition)
- •Subjects who are clinically diagnosed with probable Alzheimer's disease as defined in the NINCDS-ADRDA (National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) criteria
- •Subjects with a K-MMSE (Korea Mini-Mental State Examination) score ≤ 19 at the screening visit
- •Subjects with GDS (Global Deterioration Scale) grade 5 to 6
- •Subjects who have no other diseases to cause dementia other than AD as a result of MRI or CT scan within 12 months from the screening visit
- •Subjects who are taking donepezil alone or donepezil and memantine in combination at a stable dose without a dose change over 3 months before screening
- •Subjects who are not illiterate
- •Subjects who can walk with or without assist device to visit hospitals or clinics to undergo cognitive tests and other tests
- •Subjects with caregiver who can accompany all visits with the subjects as scheduled for this trial, supervise subject's compliance for the tests and examination process and provide information about the subject's indications, and who give written consent
排除标准
- •Subjects who have other causes of dementia as listed below according to CT/MRI test and neurologic examination within 12 months of screening or at the time of screening.
- •Subjects with possible, probable or definite vascular dementia according to NINDS-AIREN (National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences) criteria
- •Subjects with other central nervous system diseases that can cause the impairment of cognitive function (cerebrovascular disease including cerebrovascular dementia, Parkinsonism, Huntington's disease, subdural hematoma, normal pressure hydrocephalus, brain tumor, Creutzfeldt-Jakob disease, etc.)
- •Subjects with neuropathy such as delusion, delirium, epilepsy, etc.
- •Subjects who have abnormal test results which are considered to contribute to the severity of their dementia or be the cause of dementia in the vitamin B12, folic acid, syphilis serology, and the thyroid stimulating hormone (TSH) tests
- •Subjects who have a history of significant psychiatric illness such as schizophrenia or bipolar affective disorders which may interfere with the participation of this clinical trial according to the investigator's judgment or who are suffering from depression
- •Subjects with a history of known or suspected seizures including febrile seizure, recent loss of consciousness which is not explained or history of significant head trauma accompanied by loss of consciousness
- •Subjects in any medical condition that may interfere with the evaluation and progression of the clinical trial according to the investigator's judgment (acute or unstable cardiovascular disease, uncontrolled hypertension (\>160/100 mmHg) at Visit 1 and Visit 2, insulin-dependent or uncontrolled diabetes at Visit 1 (HbA1c\> 8% on screening test), etc.).
- •Subjects who are hypersensitive to the components of the investigational product.
- •Subjects with a history of alcohol and drug abuse or dependence (except nicotine dependence) within the last 2 years.
研究组 & 干预措施
GV1001 Placebo
GV1001 placebo (0.9% saline) subcutaneous injection will be administered once a week for 4 weeks and then administered every 2 weeks for 20 weeks in a double-blind phase. During the open-label extension phase, patients assigned to the GV1001 Placebo arm in the double-blind phase will receive a placebo in the first week, followed by 1.12 mg of GV1001 weekly for 4 weeks and then every 2 weeks until EOT (End of Treatment).
干预措施: GV1001 Placebo
GV1001 Placebo
GV1001 placebo (0.9% saline) subcutaneous injection will be administered once a week for 4 weeks and then administered every 2 weeks for 20 weeks in a double-blind phase. During the open-label extension phase, patients assigned to the GV1001 Placebo arm in the double-blind phase will receive a placebo in the first week, followed by 1.12 mg of GV1001 weekly for 4 weeks and then every 2 weeks until EOT (End of Treatment).
干预措施: GV1001 1.12mg
GV1001 1.12 mg
GV1001 1.12 mg subcutaneous injection will be administered once a week for 4 weeks and then administered every 2 weeks for 20 weeks in a double blind phase. During the open-label extension phase, patients will alternate between 1.12 mg of GV1001 and placebo weekly for the first 5 weeks to maintain double blindness, and then 1.12mg of GV1001 every 2 weeks until EOT.
干预措施: GV1001 Placebo
GV1001 1.12 mg
GV1001 1.12 mg subcutaneous injection will be administered once a week for 4 weeks and then administered every 2 weeks for 20 weeks in a double blind phase. During the open-label extension phase, patients will alternate between 1.12 mg of GV1001 and placebo weekly for the first 5 weeks to maintain double blindness, and then 1.12mg of GV1001 every 2 weeks until EOT.
干预措施: GV1001 1.12mg
结局指标
主要结局
Change from baseline in SIB(Severe Impairment Battery) score after GV1001 administration for 24 weeks
时间窗: Baseline, Week 26
SIB includes 51 questions to assess cognition in an individual. SIB consists of nine symptom domains such as attention, language, orientation, memory, praxis, visuospatial perception, construction, social skills and orientating head to name. The possible total scores range from 0 to 100 with a higher score indicating greater cognitive function.
CIBIC-plus (Clinician Interview-Based Impression of Change-Plus) score after GV1001 administration for 24 weeks
时间窗: Baseline, Week 26
CIBIC-plus consists of 4 items: "Overall," "Mental and Cognitive Function," "Behavior," and "Daily Function." CIBIS, a 7-point severity assessment, is administered at baseline. CIBIC-plus is implemented at follow-up visits to evaluate the degree of change in overall functional status in 7 levels by referring to the CIBIS results evaluated at baseline. The overall clinical condition of the dementia patient is assessed based on information obtained from semi-structured interviews of patients and caregivers. The rater is independent, has clinical experience, and will evaluate the subjects after completing the training required for this study.
次要结局
- Change from baseline in GDS(Global Deterioration Scale) score after GV1001 administration(Baseline, Week 6 week, Week 14, and Week 26)
- Change from baseline in ADCS-ADL-severe(Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-severe) score after GV1001 administration(Baseline, Week 6 week, Week 14, and Week 26)
- Change from baseline in SIB(Severe Impairment Battery) score(Baseline, Week 6, and Week 14)
- Change from baseline in CDR-SOB(Clinical Dementia Rating Scale Sum of Boxes) score after GV1001 administration(Baseline, Week 6 week, Week 14, and Week 26)
- CIBIC-plus (Clinician Interview-Based Impression of Change-Plus) score after GV1001 administration(Baseline, Week 6, and Week 14)
- Change from baseline in K-MMSE(Korea Mini-Mental State Examination) score after GV1001 administration(Baseline, Week 6 week, Week 14, and Week 26)
- Change from baseline in NPI-Q(Neuropsychiatric Inventory Questionnaire) score after GV1001 administration(Baseline, Week 6 week, Week 14, and Week 26)