Clinical Study to Evaluate the Efficacy and Safety of Huperzine A Controlled-Release Tablets in Patients With Mild-to-Moderate Dementia of the Alzheimer's Type

NCT07066826 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: WanbangdePharm1
• Study Type: interventional
• Target: 720
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a multicenter, randomized, double-blind, double-dummy, active- and placebo-controlled, parallel-group clinical trial. The dose confirmation stage is designed to evaluate the efficacy and safety of different doses of huperzine A controlled-release tablets in patients with mild-to-moderate dementia of the Alzheimer's type, with the goal of providing a basis for dose selection in the subsequent efficacy confirmation stage. The efficacy confirmation stage aims to assess the effect of huperzine A controlled-release tablets on cognitive function and functional abilities in patients with mild-to-moderate dementia of the Alzheimer's type.In the open-label extension stage, all subjects will receive huperzine A controlled-release tablets until Week 52, to further evaluate the long-term efficacy and safety of the treatment.

Conditions

Alzheimer Dementia

Outcome Measures

Primary Outcomes (2)

• ADAS-Cog11

  ADAS-Cog11: Alzheimer's Disease Assessment Scale-Cognitive Subscale. Score range: 0-70. Lower = better

  week24

• ADCS-ADL

  ADCS-ADL: Alzheimer's Disease Cooperative Study - Activities of Daily Living. Score range: 0-78. Higher= better

  week24

Study Arms (3)

Huperzine A controlled-release tablets

EXPERIMENTAL

Drug: Huperzine A Controlled-Release Tablets

Donepezil hydrochloride tablets

ACTIVE COMPARATOR

Drug: Donepezil hydrochloride tablets

Huperzine A controlled-release tablets placebo; Donepezil hydrochloride tablets placebo

PLACEBO COMPARATOR

Drug: Huperzine A controlled-release tablets placebo; Donepezil hydrochloride tablets placebo

Interventions

Huperzine A Controlled-Release Tablets DRUG

During the trial, the patients should take huperzine A controlled-release tablets in the morning

Huperzine A controlled-release tablets

Donepezil hydrochloride tablets DRUG

During the trial, the patients should take donepezil hydrochloride tablets before going to bed in the evening

Donepezil hydrochloride tablets

Huperzine A controlled-release tablets placebo; Donepezil hydrochloride tablets placebo DRUG

During the trial, the patients should take huperzine A controlled-release tablets placebo in the morning and donepezil hydrochloride tablets placebo before going to bed in the evening

Huperzine A controlled-release tablets placebo; Donepezil hydrochloride tablets placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject voluntarily agrees to participate in the study and signs the informed consent form jointly with a legally authorized representative (LAR). If the subject is unable to sign due to cognitive impairment or other reasons, the signature field for the subject may be left blank, with the reason specified and signed by the LAR. In such cases, the LAR must sign the informed consent form on behalf of the subject.
• Aged ≥50 and ≤85 years, male or female.
• Meets the diagnostic criteria for probable Alzheimer's disease (AD) dementia according to the 2011 National Institute on Aging and Alzheimer's Association (NIA-AA) guidelines.
• Has experienced memory impairment for at least 12 months, with a chronic and progressively worsening course.
• Has received ≥5 years of formal education and is able to complete the protocol-specified cognitive assessments.
• Diagnosed with Stage 4 or 5 (mild to moderate dementia) according to the Revised Clinical Staging of Alzheimer's Disease (2024) (i.e., Clinical Dementia Rating \[CDR\] global score of 1 or 2).
• Total score on the Mini-Mental State Examination (MMSE) is between 11 and 26 inclusive.
• Has undergone a cranial MRI scan showing a Medial Temporal Atrophy (MTA) visual rating scale grade ≥1. If the subject has completed an eligible MRI at this or another tertiary hospital within 6 months prior to screening, and it meets the protocol requirements, re-scanning is not required.
• Capable of undergoing positron emission tomography (PET) imaging.
• Hachinski Ischemic Score (HIS) ≤ 4.
• Hamilton Depression Rating Scale (HAMD-17) score of ≤10.
• No obvious focal neurological signs on physical examination, except those attributable to peripheral injury.
• Has a stable and reliable caregiver, or is in frequent contact with a caregiver (at least 4 days per week and ≥2 hours per day). The caregiver must accompany the subject to study visits, provide reliable information for scale assessments based on sufficient interaction and communication with the subject, and should remain the same throughout the study whenever possible.

You may not qualify if:

• Subjects who are allergic to the active ingredient or excipients of huperzine A controlled-release tablets or donepezil, or those with lactose intolerance.
• Cognitive impairment or dementia not caused by Alzheimer's disease (AD), including:
• (1) Other neurodegenerative diseases (e.g., dementia with Lewy bodies, frontotemporal degeneration, Huntington's disease, Parkinson's disease); (2) Non-degenerative neurological conditions causing cognitive impairment or dementia (e.g., vascular cognitive impairment or dementia, hydrocephalus, encephalitis, hypoxic brain injury, traumatic brain injury); (3) Non-neurological systemic diseases causing cognitive impairment or dementia (e.g., endocrine disorders such as hypothyroidism, hepatic insufficiency, hepatic encephalopathy, dialysis encephalopathy, neurosyphilis, HIV); (4) Cognitive impairment or dementia caused by vitamin deficiencies (e.g., folate or vitamin B12 deficiency).
• Subjects diagnosed, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with psychiatric disorders within the past 12 months that are unstable or may interfere with study assessments, including but not limited to schizophrenia or other psychotic disorders, bipolar disorder, major depressive disorder, delirium, or substance (including alcohol) use disorders with dependence.
• Subjects with significant focal brain lesions on MRI, including but not limited to any of the following (if a qualifying head MRI was performed within 6 months prior to screening and meets protocol requirements, repeat imaging is not required):
• Presence of lesions indicating large-area cerebral infarction;
• Infarcts in critical brain regions (e.g., thalamus, hippocampus, entorhinal cortex, parahippocampal gyrus, angular gyrus, cortical or subcortical gray matter nuclei);
• More than two infarcts with a diameter \>2 cm, and deemed by the investigator to impact cognitive assessments;
• Multiple lacunar infarcts, deemed by the investigator to impact cognitive assessments;
• Severe white matter lesions;
• Intracerebral hemorrhage deemed likely to affect cognitive assessments by the investigator;
• Hydrocephalus.
• Subjects with uncontrolled seizures (and/or epilepsy syndromes), or those with cognitive impairment caused or potentially caused by recurrent seizures or antiepileptic drug use.
• Subjects who experienced acute cardiovascular or cerebrovascular events within 3 months prior to screening (e.g., unstable angina, second- or third-degree atrioventricular block or other serious arrhythmias, myocardial infarction, decompensated congestive heart failure of NYHA class III or IV, transient ischemic attack, or ischemic stroke).
• Subjects with uncontrolled hypertension or hypotension at screening (defined as systolic blood pressure ≥160 mmHg or \<90 mmHg, or diastolic blood pressure ≥100 mmHg or \<60 mmHg after pharmacologic or non-pharmacologic treatment); subjects with slight deviations beyond this range but deemed clinically insignificant by the investigator may be included.

Sponsors & Collaborators

• Wanbangde Pharmaceutical Group Co., LTD: lead

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Central Study Contacts

Juan Li

CONTACT

+8613735826039; lijuan@wepon.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2025
• First Posted: July 15, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): August 15, 2028
• Last Updated: July 15, 2025

Record last verified: 2025-06