Early Alzheimers disease
Conditions
Interventions
VHB937 10 mg/kg:VHB937
VHB937 30 mg/kg:VHB937
placebo:NA
Sponsors
Huashan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
50 Years to 85 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. Male and female participants 50 to 85 years of age, with a maximum body weight of 180kg at the time of signing the informed consent. 3. Diagnosis of Mild Cognitive Impairment (MCI) due to AD or mild AD according to theNational Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria(Jack et al 2018) at Screening. 4. Clinical Dementia Rating (CDR) Global score of 0.5 or 1.0 at Screening and Baseline. 5. ADAS-Cog14 total score between 13 and 54 (inclusive) at Screening. 6. Biomarker-based confirmation of Alzheimer disease (AD) at Screening based on cerebra lspinal fluid (CSF) biomarkers or amyloid PET imaging. Historical confirmation of amyloid positivity by CSF or PET is accepted. 7. Fluency in local language in which study assessments are administered and evidence of adequate pre-morbid intellectual functioning and adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments; 8. Reliable study partner such as spouse, sibling, close friend, or caregiver who can accompany the participant at study visits in which informant scales are administered. The study partner should be fluent in and able to read the local language in which study assessments are administered and also willing and able to provide information to study Investigator/staff. The study partner must, in the opinion of the Investigator, spend sufficient time with the participant on a regular basis such that this person can reliably fulfill the study requirements. There should be no foreseeable plan for the study partner to change during the Double-blind period. 9. Participants receiving an acetylcholinesterase inhibitor (AChEI) or memantine or both for AD must be on a stable dose for at least 12 weeks prior to Randomization. For participants who discontinued these medications before Screening, the stop date should be at least 12 weeks before Randomization. Treatment-naïve participants can also be enrolled into the study.
Exclusion criteria
Exclusion criteria: 1. Dementia due to a condition other than AD including, but not limited to, frontal temporal dementia (FTD), Parkinson's disease, dementia with Lewy bodies, Huntington disease, vascular dementia. 2. APOE4 HM status. Participants with APOE4 HM status will be allowed only after DMC safety review and following positive recommendation from data monitoring committee (DMC). 3. Prior or current treatment with an anti-amyloid antibody. 4. Transient ischemic attacks (TIA) or stroke occurring within 12 months prior to randomization. 5. Other significant neurological disease affecting the central nervous system other than dementia, that may affect cognition or ability to complete the study, including but not limited to, serious infection of the brain, traumatic brain injury, multiple concussions,epilepsy or recurrent seizures (except febrile childhood seizures). 6. Any current primary diagnosis of psychiatric disorder or symptom that in the judgment of the Investigator is likely to confound the interpretation of drug effect, affect cognitive assessment, or affect the participant capability to complete the study. Participants with a current major depressive episode that based on Investigator assessment is not adequately controlled and participants with history of schizophrenia and other chronic psychosis are excluded. 7. Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening or a positive urine drug test at Screening. Participants who test positive for benzodiazepines or opioids in urine drug testing do not need to be excluded if, in the clinical opinion of the Investigator, this is due to prior/concomitant medications containing benzodiazepines or opioids for a medical condition and not due to drug abuse. 8. Answer "Yes" to Suicidality assessment to Columbia Suicide Severity Rating Scale (CSSRS) Suicidal ideation items 4 or 5, if this ideation occurred in the past 6 months or "Yes" on any item of the Suicidal behavior section, if this behavior occurred in the past 2 years before Screening; answer "Yes" to Suicidal ideation items 4 or 5 and "Yes" on any item of the Suicidal behavior at Baseline will also be exclusionary. 9. Abnormally low serum vitamin B12 levels in central laboratory results at Screening (if participant is taking vitamin B12 injections level should be at or above the lower limit of normal). 10. Uncontrolled thyroid disease or uncontrolled diabetes or clinically significant laboratory abnormalities for thyroid function or fasting glucose in central laboratory results at Screening, as assessed by Investigator. The Investigator should ensure that the diabetic participants remain adequately controlled during the study. 11. Active hepatitis B virus (HBV) (hepatitis B surface antigen and total anti-HB core antibody positive), active hepatitis C virus (HCV) (HCV-RNA positive), human immunodeficiency virus positivity (HIV) (HIV antigen or antibody positive) in central laboratory results at Screening or signs/symptoms of a clinically significant systemic viral, bacterial, or fungal infection within 4 weeks prior to the Screening visit (for such cases, participants can be re-screened upon resolution). For Japanese participants, according to the guideline of Japan Society of Hepatology (Drafting Committee for Hepatitis Management Guidelines the Japan Society of Hepatology 2020), in addition to the above criteria: in the absence of a positive history of HBV vaccination, participants with positive hep
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objectives: To evaluate the effect of VHB937 compared to placebo on cognition and function; | — |
Secondary
| Measure | Time frame |
|---|---|
| Adverse event; | — |
Countries
China
Contacts
Public ContactJintai Yu
Huashan Hospital, Fudan University
Outcome results
None listed