The Clinical Study of Synaptic Plasticity-based Lencanumab for the Treatment of Early Alzheimer's Disease

NCT06871839 | Recruiting FDA Drug

• 1 other identifier: KS2024354
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Alzheimer's disease (AD) manifests itself in cognitive decline, impaired ability to perform daily life, and a variety of behavioral and psychiatric symptoms, seriously endangering the health of the elderly. The prevalence and disability rates of AD in China remain high, and the lack of effective treatment options has brought a heavy burden to patients and their families. Early intervention is regarded as an effective strategy to improve clinical symptoms, delay disease progression and maintain current quality of life. The humanized monoclonal antibody lencanemab (Lecanemab) was approved by the U.S. FDA in July 2023 for the treatment of mild cognitive impairment or mild dementia caused by AD, and was officially approved in January 2024 in China. Lencanemab highly targets soluble and insoluble neurotoxic β-amyloid (Aβ) proteins, reducing pathogenic Aβ plaque deposition and preventing its formation in the brains of AD patients, thus reducing neurotoxicity and improving patients' cognitive functions. In addition, lencanumab may also play a neuroprotective role by modulating synaptic plasticity and regulating neural network activity in brain neurons. However, there is a lack of clinical studies to prove this mechanism. In this study, we will enroll consecutive patients with early AD treated with lencanemab infusion as well as those receiving conventional anti-dementia therapy, and comprehensively assess the effects and intrinsic molecular mechanisms of lencanemab on synaptic function and neural networks using magnetic resonance imaging, molecular imaging positron emission tomography (PET), neuropsychological assessment, and analysis of blood cerebrospinal fluid samples.

Conditions

Alzheimer's Disease; Lecanemab; Functional Magnetic Resonance Imaging

Keywords

Alzheimer's disease; Lecanemab; functional magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• Resting-state fMRI brain network metrics (Independent Component Analysis)

  The Lecanemab treatment group and the conventional treatment group's longitudinal changes in Independent Component Analysis (ICA) indicators after 12 months of treatment compared to baseline. ICA is a statistical technique used for extracting mutually independent signals from multivariate data, capable of measuring levels of functional connectivity within and between networks.

  2 years

Secondary Outcomes (19)

• Other resting-state fMRI brain network indicators: functional connectivity (FC)

  2 years

• Other resting-state fMRI brain network indicators: Granger Causality Analysis (GCA)

  2 years

• Other resting-state fMRI brain network indicators: Spectral Dynamic Causal Model (spDCM)

  2 years

• Rate of change in global cognition as measured by Clinical Dementia Rating (CDR)

  2 years

• Rate of change in the severity of cognitive impairment as assessed by Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog)

  2 years

Other Outcomes (1)

• Blood neuron-derived exosome transcriptomics-related indicators

  2 years

Study Arms (2)

Lecanemab treatment group

Early-stage Alzheimer's disease patients are given Lecanemab infusion treatment in conjunction with conventional anti-dementia drug therapy.

Drug: Lecanemab treatment group

Conventional anti-dementia treatment

Early-stage Alzheimer's disease (AD) patients commonly take cholinesterase inhibitors such as donepezil for treatment.

Drug: Conventional anti-dementia treatment group

Interventions

Lecanemab treatment group DRUG

Lecanemab treatment group: Lecanemab Injection Concentrate Solution (active ingredient at 100 mg/mL) is provided as a sterile aqueous solution containing 100 mg/mL of Lecanemab, 50 mmol/L citric acid, 350 mmol/L arginine/arginine hydrochloride, and 0.05% (w/v) polysorbate 80, with a pH of 5.0, and each vial is capable of being drawn into a volume of 5 mL. Lecanemab is to be administered via intravenous infusion over 60 minutes in saline solution. Lecanemab must be administered using an infusion system that includes a terminal 0.22 μM inline filter. The dosage of Lecanemab is 10 mg/kg. All subjects in the Lecanemab treatment group receive Lecanemab infusion therapy at a frequency of once every two weeks for a continuous period of 12 months.

Lecanemab treatment group

Conventional anti-dementia treatment group DRUG

Conventional anti-dementia treatment: Early-stage Alzheimer's disease (AD) patients routinely take cholinesterase inhibitors such as donepezil for treatment.

Conventional anti-dementia treatment

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

We will recruit 120 early Alzheimer's disease (AD) patients from 13 hospitals, including Xuanwu Hospital of Capital Medical University. Among them, 60 cases will be in the Lecanemab treatment group, and 60 cases in the conventional treatment group.

You may qualify if:

• Age between 50 and 90 years.
• Male or female patients.
• Patients with MCI and mild AD.
• MMSE score ≥20, CDR overall score of 0.5 or 1.
• Amyloid-positive confirmed by Amyloid-PET or CSF.
• Have a reliable caregiver to accompany the patient during study visits and supervise the use of study medication during the trial.
• Agree to participate in the study and sign the informed consent form.

You may not qualify if:

• Patients with cognitive impairment due to reasons other than AD.
• A history of transient ischemic attack (TIA), stroke, cerebral hemorrhage, or seizure within the 12 months prior to screening.
• A score of \>17 on the Hamilton Depression Scale at screening, or any suicidal behavior within 6 months prior to screening, at screening, or at the baseline visit, as well as any psychiatric diagnosis or symptoms that interfere with the study procedure (such as hallucinations, anxiety disorder, or paranoia).
• Patients with a bleeding disorder or receiving anticoagulant therapy, as well as any with malignant tumors, severe gastrointestinal, kidney, liver, respiratory, immune, endocrine, and cardiovascular system diseases that affect this study.
• A hypersensitivity reaction to ranucimab or any other ingredient in the injection solution, or to any monoclonal antibody treatment.
• Contraindications to MRI scanning, including those with a pacemaker/defibrillator or ferromagnetic metal implants (except for skull and cardiac devices approved as safe for MRI scanning).
• A known or suspected history of drug or alcohol abuse or dependence within the 2 years prior to screening.
• Participation in a clinical study involving any therapeutic monoclonal antibody or novel compounds for the treatment of AD within the 6 months prior to screening, unless it can be proven that the subject was in the placebo treatment group.
• Planning to undergo surgery requiring general anesthesia during the study period.
• A positive pregnancy test result, lactation, or pregnancy in females at screening or baseline.

Sponsors & Collaborators

• Cuibai Wei，Clinical Professor: lead
• Eisai (China) Pharmaceutical Co.: collaborator
• Jinan Hospital, Xuanwu Hospital, Capital Medical University: collaborator
• RenJi Hospital: collaborator
• First Hospital of China Medical University: collaborator
• Nanjing Brain Hospital: collaborator
• Guangdong Provincial People's Hospital: collaborator
• Zhejiang University: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• The First Affiliated Hospital of University of Science and Technology of China: collaborator
• The First Hospital of Chongqing Medical University: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• West China Hospital: collaborator
• The First Hospital of Jilin University: collaborator

Study Sites (1)

Capital Medical University Xuanwu Hospital

Beijing, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood samples, CSF

Study Officials

• Cui bai Wei

  Xuan Wu Hospital of Capital Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cui bai Wei

CONTACT

83198319; weicb@xwhosp.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor, chief physician

Study Record Dates

• First Submitted: March 7, 2025
• First Posted: March 12, 2025
• Study Start: March 10, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 22, 2025

Record last verified: 2025-03

Locations

CN (1)