Recombinant Human Serum Albumin in the Treatment of Mild-to-moderate AD (Alzheimer's Disease) Exploratory Clinical Trial

An Open-label, Parallel-group Exploratory Clinical Trial to Evaluate the Safety and Preliminary Efficacy of Recombinant Human Serum Albumin Injection in the Treatment of Mild-to-moderate Alzheimer's Disease

This clinical trial is an open-label, parallel-group, exploratory study of recombinant human serum albumin in patients with mild to moderate Alzheimer's Disease (AD).

This clinical trial is an open-label, parallel-group, exploratory study of recombinant human serum albumin in patients with mild to moderate Alzheimer's Disease (AD). It aims to enroll 30 participants who meet the 2011 National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for "Probable AD Dementia." Participants will be randomized in a 1:1:1 ratio to receive the investigational drug at doses of 20g, 30g, or 40g, for assessments of safety and preliminary efficacy. Stratification factors will be based on the severity classification (mild; moderate) as indicated by the total score on the Clinical Dementia Rating Scale - Global Score (CDR-GS) during the screening period.

Inclusion Criteria：

1. Aged between 50 and 85 years (inclusive), with no gender restrictions;
2. Meet the 2011 National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for "Probable AD Dementia";
3. The severity of the disease was mild or moderate, that is, 1 ≤ Clinical dementia scale total score (CDR-GS) score ≤ 2;
4. Hachinski Ischemia Scale (HIS) ≤ 4;
5. Geriatric Depression Scale (GDS) score between 0 and 20 (inclusive);
6. Memory impairment present for at least 12 months with evidence of progression;
7. Previous PET CT/MRI scan can be provided to confirm the diagnosis of AD at the time of screening. We may provide qualified head MRI films or head MRI plain scan and oblique coronal hippocampal scan within 12 months: The likelihood of Alzheimer's disease on MRI was highest when there were fewer than or equal to two infarcts larger than 2 cm in diameter and no infarcts in key areas such as the thalamus, hippocampus, entorhinal cortex, parorhinal cortex, angular gyrus, cortex, or other subcortical gray matter nuclei (Medial Temporal Atrophy Visual Rating Scale [MTA] grade of 2 or greater);
8. Female participants must be postmenopausal for at least 24 weeks, have undergone sterilization surgery, or if of childbearing potential, along with fertile males, agree to use effective contraception during the study. Women of childbearing potential or those postmenopausal for less than 24 weeks require a negative pregnancy test at screening;
9. If patients were on Alzheimer's medications such as cholinesterase inhibitors, NMDA receptor antagonists, or Oligomannate capsules, or taking other drugs that could affect cognition (e.g., Ginkgo biloba, Ginkgo leaf extract, Vitamin E, Selegiline, Folic acid, Estrogen, traditional Chinese medicines including compound sea snake capsules, Citicoline, Piracetam, Aniracetam, etc.), they must have been on a stable dose for at least 30 days before screening, with the investigator determining suitability and the patient agreeing to maintain this stable dose throughout the trial;
10. Patients must have a stable and dependable caregiver or adequate care arrangements (a minimum of 4 days weekly, 2 hours daily), with the caregiver willing to assist in the patient's full participation in the trial, including accompanying them to visits and helping with assessment scales;
11. Patients should have an educational level of primary school completion or above, capable of completing cognitive assessments and other tests as required by the protocol;
12. Written informed consent obtained.

Exclusion Criteria:

1. Investigators believe that the main causes of cognitive impairment are frontotemporal dementia, dementia with Lewy bodies, vascular dementia, dementia caused by Parkinson's disease, dementia caused by epilepsy, dementia caused by craniocerebral injury, and dementia related to central nervous system infection and immunity;

2. Known history of allergy or allergic reactions to yeast or yeast-derived products, any component of the study formulation, individuals with an allergic constitution (multiple drug or food allergies), a history of severe systemic allergic reactions to biologics, or those deemed unsuitable for trial drug treatment by the investigator;

3. Active or historical cardiovascular disorders at screening or conditions deemed inappropriate for human albumin treatment by the investigator, specifically including but not limited to: hypertension (systolic blood pressure >160 mmHg or diastolic >100 mmHg, unless well-controlled with medication and stable in the investigator's judgment), severe anemia, acute cardiac events, significant heart or pulmonary structural diseases, severe arrhythmias, decompensated heart failure (in normal or high volume states), unstable angina, myocardial infarction within 6 months prior to screening, medically treated tachycardia/bradycardia, third-degree atrioventricular block, etc.;

4. Active metabolic disorders or history thereof at screening, or concurrent renal impairment deemed unsuitable for serum albumin therapy by the investigator, such as diabetic kidney disease, hyperuricemia-related renal injury, sleep apnea-associated renal damage, hyperlipidemia-induced renal impairment, etc.;

5. Presence of severe underlying diseases at screening that the investigator deems inappropriate for study participation, including but not limited to active malignancy, pulmonary edema, bleeding tendencies or active bleeding disorders, uncontrolled infections (including spontaneous bacterial peritonitis), thyroid dysfunction (Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE], version 5.0), etc.;

6. Positive for hepatitis B surface antigen (HBsAg), positive for hepatitis B core antibody (HBcAb) with detectable hepatitis B virus deoxyribonucleic acid (HBV-DNA), positive for hepatitis C antibody (HCV Ab) with detectable hepatitis C ribonucleic acid (HCV-RNA), positive for human immunodeficiency virus antibody (HIV Ab), or positive for Treponema pallidum (syphilis) antibodies at screening;

7. Presence of the following laboratory abnormalities at screening:

   • Liver function: Alanine transaminase (ALT) >3 times the upper limit of normal (ULN); Aspartate transaminase (AST) >3 ULN; Total bilirubin (TBIL) >1.5 ULN or deemed unsuitable for the trial by the investigator;
   • Renal function: Creatinine clearance (Ccr) <50 mL/min (calculated using the Cockcroft-Gault formula: Ccr(mL/min) = [(140 - age) × weight(kg)] / [72 × Scr(mg/dL)], multiplied by 0.85 for females);
   • Bone marrow function: Absolute neutrophil count (ANC) <1.5 × 10^9/L; Platelets (PLT) <100 × 10^9/L; Hemoglobin (HGB) <90 g/L;

8. Patients had or had a history of a neurological disease at the time of screening, such as a neurological disease with unstable control;

9. Patients with coexisting psychiatric conditions, including schizophrenia or other psychiatric conditions, bipolar disorder, and depression or delirium not due to Alzheimer's disease, were assessed by the investigator as being ineligible for the trial;

10. Contraindications to MRI scanning, including incompatible cardiac pacemakers/defibrillators, magnetic metal implants, etc.;

11. Irreversible visual or auditory impairments preventing completion of assessments related to cognition, neuropsychiatric symptoms, and activities of daily living;

12. Alcohol or drug abusers;

13. Pregnant or lactating women;

14. Received plasma derivatives (including human albumin) within 3 months prior to screening, history of organ transplantation, or planned to undergo invasive procedures or treatments during the study;

15. Participated in another clinical trial (excluding non-drug intervention trials) within 30 days prior to the screening visit for this trial or planning to participate in another trial during this study;

16. The investigator judges that the AD patient is unlikely to complete the trial, such as poor adherence to medication or scheduled visits.