Alzheimer's Disease
Conditions
Interventions
All eligible participants will be randomized in a 1:1 ratio to GV-971 and
placebo groups.
Both GV-971 and placebo will be administered orally, twice a day.
The dose of the product will be 450mg twi
Sponsors
Green Valley (Shanghai) Pharmaceuticals Co., Ltd.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male and female participants aged 50 to 85 years (inclusive) at the time of screening. 2. Willing and able to give informed consent by GCP and local guidance. If the study participant is not competent to give informed consent, in the opinion of the principal investigator, a legally authorized representative (per applicable laws, rules, and regulations) must provide informed consent on his/her behalf, and the participant must provide assent (or local equivalent). 3. Mild to moderate AD as characterized by the following clinical, cognitive, and functional criteria per National Institute on Aging - Alzheimer's Association (NIA-AA) diagnostic criteria (refer to Section 11.5 for additional details). a. Clear history of cognitive and functional decline over at least 1 year that is either (1) documented in medical records or (2) documented by history taken from a study partner or other person who knows the participant well (eg, personal physician). b. MMSE scores between 11 and 24, inclusive, at screening and at baseline. Note: Screening MMSE must be performed after obtaining consent. 4. Have a study partner/caregiver who has known the participant for at least 1 year and assists the participant regularly at least 3 times per week and has intimate knowledge of the participant's cognitive, functional, and emotional states and of the participant's personal care. The study partner must be willing to accompany the participant to all study visits, assure that all of the participant's medications and the study drug are stored and dispensed safely, and report adverse events. The study partner must be willing and able to give informed consent for their own participation, be able to read and write, and be capable of providing partner responses to scales such as ADL scales, ADCS-CGIC, and NPI. Note: Use of the same study partner/caregiver during the study period is encouraged. Any change in study partner/caregiver should be recorded with reasons detailed in the medical chart and case report form (CRF). Informed consent must be obtained from the new study partner/caregiver. 5. Investigator confirmation of participant's ability to complete efficacy assessments and have physical, cognitive, hearing, speech, literacy, and language capacity to participate in all testing. 6. A brain magnetic resonance imaging (MRI) scan during screening. All imaging is evaluated by a central reader vendor (refer to imaging manual for details). MRI will have oblique coronal hippocampus scan and must show the highest possibility of AD, including: a. Medial temporal lobe atrophy visual rating scale (MTA) * grade 2 by central read; b. Fazekas scale for white matter lesions grade 24 months), surgically sterilized, or of childbearing potential who agree to take highly effective contraceptive measures throughout the study (see Section 9 for details regarding contraception). Women of childbearing potential (WOCBP) must undergo a urin
Exclusion criteria
Exclusion criteria: 1. Diagnosis of a dementia-related central nervous system disease other than AD (eg, Parkinson's Disease, Huntington's Disease, frontotemporal dementia, multi-infarct dementia, dementia with Lewy bodies, normal pressure hydrocephalus). 2. Abnormally low folate, thyroid, and/or vitamin B12 values or evidence of hypothyroidism thought to be the cause of or to contribute to the severity of the participant's dementia. 3. Abnormalities found on brain MRI, including ischemic and hemorrhagic infarctions, hydrocephalus, and brain tumors will be flagged for discussion with the Medical Monitor. The NIA-AA criteria will be applied to determine if vascular lesions are exclusionary. NOTE: CT scan may be substituted, with similar review by central reading when there are MRI contraindications such as heart valve replacement, pacemaker, or implants, if medical monitor approves. CT, unlike MRI, would not be repeated in double-blind or OLE period (see Section 8.2.7.4). 4. Mental/psychiatric illness determined by Diagnostic and Statistical Manual of Mental Disorders (DSM) V criteria, that is unstable within 12 months, or would interfere with study assessments, including schizophrenia or other psychotic disorders, bipolar disorder, severe depression, or delirium. 5. History of suicidal actions within the past 12 months or current suicide risk determined by a positive response ('Yes') to either Question 4 or Question 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening. 6. DSM V diagnosis of alcohol or other substance abuse dependence within the last 12 months. 7. Gastrointestinal illness that may substantially impact absorption such as gastric bypass or recurrent diarrhea. 8. History within the last 12 months or current diagnosis of clinically significant cardiovascular or cerebrovascular diseases/disorders such as serious cardiac arrhythmias, heart rate abnormalities, myocardial infarction, well-documented transient ischemic attack, or cerebrovascular accident, uncompensated congestive heart failure New York Heart Association class III and IV. 9. A resting heart rate of 3 years from the screening. b. Basal cell or stage 1 squamous cell carcinoma of the skin or stable untreated cancer such as prostate or meningioma. c. Chronic carcinomas that do not require treatment (eg, prostate carcinoma restricted to the prostate). 12. Any participants who have previously been treated with GV-971 but discontinued due to safety issues or lack of efficacy. 13. Any participants who have taken any dose of GV-97
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1 Change from baseline to End of Double-blind Study (EODB) in Alzheimer's Disease Assessments Scale * cognitive subscale/11-item (ADAS-cog/11) score. 2 Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) scale total score at EODB. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change from baseline to Weeks 36, and 52 in Neuropsychiatric Inventory (NPI) score. 2. Change from baseline to EODB in Mini Mental State Examination (MMSE) score. 3. End point * Change from baseline to Weeks 36 and 52 in Alzheimer's Disease Cooperative Study * Activities of Daily Living; 23-item Scale (ADCSADL23). * Change from baseline to Weeks 36 and 52 in Amsterdam Instrumental Activities of Daily Living scale (A-IADL). 4. Change from baseline to Weeks 12, 24, and 36 in ADAS-cog/11 and ADCS-CGIC scores. 5. end point * Incidence of treatment emergent adverse events (TEAEs) and SAEs * Vital signs * Clinical laboratory values * Physical exam findings * Electrocardiogram (ECG) * Brain magnetic resonance imaging (MRI) * Columbia-Suicide Severity Rating Scale (C-SSRS) * Change from baseline in Zarit Burden Interview (ZBI). * Change from baseline in NPI caregiver items. 6. End point * Change from baseline in the primary and secondary caregiver time components of the Resource Utilization in Dementia (RUD) * Lite Version * The change from baseline in the RUD-Lite total score 7. Changes from baseline through End of Study (EOS) and from Week 52 to Week 78 in: o ADAS-cog/11, o ADCS-CGIC, o NPI, o MMSE, o ADCS-ADL23, o A-IADL, o Incidence of adverse events (AEs), o Vital signs, o Clinical laboratory values, o Physical exam findings, o Electrocardiogram (ECG), oMRI - for safety, o Columbia-Suicide Severity Rating Scale (C-SSRS). | — |
Countries
Netherlands
Outcome results
None listed