Study of 50561 in Patients With Mild or Moderate Alzheimer's Disease

NCT05811442 | Completed Phase 2 DMC

• 1 other identifier: 50561-II-01
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 12

Brief Summary

This is a multi-center, Phase IIa, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety of two doses of 50561 compared to placebo in participants diagnosed with mild to moderate Alzheimer's disease.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease; 50561; Rac1

Outcome Measures

Primary Outcomes (1)

• Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog 13)

  Change from baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog 13) at 24 weeks. The total score ranges from 0 to 85, with higher scores representing worse outcome.

  24 weeks

Secondary Outcomes (6)

• Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog 13)

  6 weeks, 12 weeks

• Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)

  6 weeks, 12 weeks, 24 weeks

• Mini-Mental State Examination (MMSE)

  6 weeks, 12 weeks, 24 weeks

• Alzheimer's Disease Collaborative research group-Activities of Daily Living (ADCS-ADL)

  6 weeks, 12 weeks, 24 weeks

• Neuropsychiatric Inventory (NPI)

  6 weeks, 12 weeks, 24 weeks

Study Arms (3)

50561 256mg

EXPERIMENTAL

50561 at a dose of 256mg n=20 group

Drug: 50561 high dose

50561 128mg

EXPERIMENTAL

50561 at a dose of 128mg n=20 group

Drug: 50561 low dose

placebo

PLACEBO COMPARATOR

Placebo n=20 group

Drug: Placebo

Interventions

50561 high dose DRUG

study drug

50561 256mg

50561 low dose DRUG

study drug

50561 128mg

Placebo DRUG

Non-active study drug

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:

• Agree to participate and sign the informed consent form (ICF) with a legal guardian;
• Male or female subjects aged 50-85 years (inclusive), at the time of informed consent;
• Subjects have received education in primary school and above and are able to complete protocol specified cognitive ability test and other tests;
• Meets the National Institute on Aging -Alzheimer's Association (NIA-AA) core clinical criteria (2011) for probable Alzheimer's disease (AD) dementia;
• Impaired memory for at least 12 months, with a tendency of progressive aggravation;
• Treatment-naive subjects for Alzheimer's disease (AD);
• Mild to moderate Alzheimer's disease (AD):
• (1) Mini-Mental State Examination (MMSE) score of ≥ 11 and \< 26 (2) Clinical Dementia Rating-Global Score (CDR-GS) of 1 or 2;
• \. Hachinski Ischemic Scale (HIS) score of ≤ 4;
• \. Hamilton Depression Rating Scale (HAMD) (17-item version) score of ≤ 10;
• \. Cranial magnetic resonance imaging (MRI) plain scan and oblique coronal hippocampal scan:
• Age-adjusted medial temporal lobe atrophy scale \[MTA scale\] score: Score 2 or more for \< 75 years, score 3 or more for ≥ 75 years;
• Infarction lesions larger than 2 cm in diameter ≤ 2
• Without infarction lesion in vital sites, such as the thalamus, hippocampus, entorhinal cortex, paraolfactory cortex, angular gyrus, cortex, and other subcortical gray matter nuclei;
• Fazekas Scale ≤ 2.

You may not qualify if:

• Dementia caused by other reasons: Vascular dementia, central nervous system infection (e.g., AIDS, syphilis), Creutzfeldt-Jakob disease, Huntington's disease, Parkinson's disease, Lewy body dementia, brain trauma dementia, other physical and chemical factors (e.g., drug poisoning, alcohol poisoning, carbon monoxide poisoning), important corporeal diseases (e.g., hepatic encephalopathy, pulmonary encephalopathy), intracranial space-occupying lesions (e.g., subdural hematoma, brain tumors), endocrine system disorders (e.g., thyroid disease, parathyroid disease ) and dementia due to vitamin deficiency or any other known causes;
• Previously had/currently has nervous system disorder (including Neuromyelitis optica, Parkinson's disease, epilepsy);
• Mental disorders confirmed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), including schizophrenia or other mental illness, bipolar disorder, major depression, or delirium;
• Laboratory test abnormalities at screening visit and baseline: Liver function (alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\]) \> 2-fold the upper limit of normal (ULN); Kidney function (creatinine \[Cr\]) \> 1.5-fold the ULN; Creatine kinase (CK) \> 2-fold the ULN; Patients with values that slightly exceed these ranges but are not clinically significant may be included as assessed by the investigator;
• Presence of any one of the following infections at the screening visit:
• (1) Positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV-DNA) (exceeding the upper limit of the normal range of the study site); (2) Positive for anti-hepatitis C virus (HCV) antibody (Ab); (3) Positive for human immunodeficiency virus (HIV) Ab; (4) Positive for Treponema pallidum (TP) Ab;
• \. Presence of other active and poorly managed systemic bacterial, viral, fungal, or parasitic infections (except for fungal nail infection) at the screening visit, or other clinically significant active infections that render the subject unsuitable for study participation as assessed by the investigator;
• \. Systolic blood pressure (SBP) ≥ 160 mmHg or \< 90 mmHg or diastolic blood pressure (DBP) ≥ 100 mmHg or \< 60 mmHg at the screening visit and baseline; Patients with SBP or DBP that slightly exceed this range but is not clinically significant may be included as assessed by the investigator;
• \. Prolonged corrected QTc interval (Fridericia formula, Appendix 14.1) in the 12-lead electrocardiography (ECG) at screening visit and baseline: Fridericia corrected QT interval (QTcF) \> 450 ms for males and \> 470 ms for females or other clinically significant ECG abnormalities that render the subject unsuitable for study participation (e.g., heart rate \< 50 beats/min, sinus node dysfunction, Mobitz II or third-degree atrioventricular block);
• \. Patients with unstable or severe cardiovascular, respiratory, digestive, urinary, hematologic, or endocrine disorders within 6 months prior to the screening visit, including pancreatitis, severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, life-threatening ventricular arrhythmia requiring maintenance therapy, pulmonary hypertension, respiratory failure, previous hypoglycemia coma, unstable blood glucose control in diabetic patients, and stroke (including transient ischemic attack), and are unsuitable for study participation as assessed by the investigator;
• \. Presence of gastrointestinal disorder that, as assessed by the investigator, can impact drug absorption or metabolism within 6 months prior to the screening visit;
• \. Underwent major surgery within 6 months prior to the screening visit that renders the patient unsuitable for enrollment or planning to undergo major surgery during the study;
• \. Suffered from a malignant tumor within 3 years prior to the screening visit (excluding resected basal cell carcinoma or cutaneous squamous cell carcinoma , and/or resected carcinoma in situ);
• \. Received other traditional Chinese or Western nootropic medications/treatments within 4 weeks prior to baseline;
• \. Use of strong CYP3A4 inhibitor or strong CYP3A4 inducer within 4 weeks or 5 half-lives (whichever is longer) prior to baseline;

Sponsors & Collaborators

• Beijing Joekai Biotechnology LLC: lead

Study Sites (12)

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, 100053, China

Location

Beijing Anding Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, China

Location

Heilongjiang Provincial Hospital of Traditional Chinese Medicine

Haerbin, Heilongjiang, China

Location

Wuhan Union Hospital of China

Wuhan, Hubei, China

Location

The Second Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Location

The First affiliated hospital of SOOCHOW university

Suzhou, Jiangsu, China

Location

The First Bethune Hospital of Jilin University

Changchun, Jilin, China

Location

Tianjin Huanhu Hospital

Tianjin, Tianjin Municipality, China

Location

Sir Run Run Shaw Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Jianping Jia

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

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: March 28, 2023
• First Posted: April 13, 2023
• Study Start: April 18, 2023
• Primary Completion: August 22, 2025
• Study Completion: September 11, 2025
• Last Updated: September 18, 2025

Record last verified: 2025-09

Locations

CN (12)