Recombinant Human Serum Albumin in the Treatment of AD (Alzheimer Disease) Exploratory Clinical Trials

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).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease (AD)
• Intervention / Treatment: Drug: Recombinant Human Serum Albumin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Luoyang, Henan, China, 471002
      • Luoyang Third People's Hospital
    • Zhengzhou, Henan, China, 450000
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Wuhan Union Hospital of China
  • Jiangxi
    • Jiujiang, Jiangxi, China, 332000
      • Clinical Medical College & Affiliated Hospital Of Jiujiang University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 20g dose group; Administered intravenously once every 3 weeks, until 25 weeks (or 37 weeks if the treatment period was extended)	Drug: Recombinant Human Serum Albumin; Each group receives the investigational drug (recombinant human serum albumin), with the distinction being the variation in dosing.
Experimental: 30g dose group; Administered intravenously once every 3 weeks, until 25 weeks (or 37 weeks if the treatment period was extended)	Drug: Recombinant Human Serum Albumin; Each group receives the investigational drug (recombinant human serum albumin), with the distinction being the variation in dosing.
Experimental: 40g dose group; Administered intravenously once every 3 weeks, until 25 weeks (or 37 weeks if the treatment period was extended)	Drug: Recombinant Human Serum Albumin; Each group receives the investigational drug (recombinant human serum albumin), with the distinction being the variation in dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	The primary objective of the trial was to evaluate safety according to the type, incidence, and severity of adverse events, which were graded with the use of the NCI CTCAE V5.0.	41 Weeks
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score	Change from Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) at Week 25 Post-Treatment.	25 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) scores from baseline at Weeks 7, 16, 29 (if applicable), 37 (if applicable), and 41 (if applicable) post-treatment.	The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) is an instrument used to assess cognitive function in individuals with Alzheimer's disease or other forms of dementia. The scale ranges from 0 to 70, with lower scores indicating better cognitive function and higher scores indicating more severe cognitive impairment. Therefore, the lower the score on the ADAS-Cog, the better the cognitive performance of the individual being assessed. Conversely, a higher score indicates greater cognitive decline. The minimum possible score on the ADAS-Cog is 0, and the maximum possible score is 70.	At Weeks 7, 16, 25, 29 (if applicable), 37 (if applicable), and 41 (if applicable)
The changes in Clinical Dementia Rating Scale - Global Score (CDR-GS) from baseline at Weeks 7, 16, 25, 29 (if applicable), 37 (if applicable), and 41 (if applicable) following treatment initiation.	The Clinical Dementia Rating - Global Score (CDR-GS) is a tool used by healthcare professionals to assess the severity of dementia in patients. The CDR-GS has a range from 0 to 3, with 0 representing no dementia, 0.5 indicating very mild dementia, 1 indicating mild dementia, 2 indicating moderate dementia, and 3 indicating severe dementia. Therefore, the lower the score on the CDR-GS, the better the cognitive and functional abilities of the individual being assessed. Conversely, a higher score indicates more severe dementia. The minimum possible score on the CDR-GS is 0, and the maximum possible score is 3.	At Weeks 7, 16, 25, 29 (if applicable), 37 (if applicable), and 41 (if applicable)
The changes in Neuropsychiatric Inventory (NPI) scores from baseline at Weeks 7, 16, 25, 29 (if applicable), 37 (if applicable), and 41 (if applicable) after the commencement of treatment.	The Neuropsychiatric Inventory (NPI) is a tool used to evaluate neuropsychiatric symptoms in individuals with dementia. A lower score on the NPI indicates fewer or less severe neuropsychiatric symptoms, while a higher score suggests more frequent or severe symptoms. Thus, a lower NPI score is generally considered to be a better outcome. The minimum possible score is 0, and the maximum possible score is 144.	At Weeks 7, 16, 25, 29 (if applicable), 37 (if applicable), and 41 (if applicable)
The changes in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) ability assessment scale scores from baseline	The Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) is a tool designed to measure the functional ability of individuals with Alzheimer's disease. The ADCS-ADL has a range from 0 to 78, where 0 indicates complete dependence and 78 indicates complete independence. Higher scores on the ADCS-ADL indicate better functional status and ability to perform daily activities independently.ng the start of treatment.	At Weeks 7, 16, 25, 29 (if applicable), 37 (if applicable), and 41 (if applicable)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AD associated biomarkers	or each dose group, lumbar puncture to collect approximately 5 mL cerebrospinal fluid (CSF) will be performed in ≥50% of subjects (subject selection to be determined by the investigator based on individual patient conditions) after any dose administration between Baseline and Day 1 of Week 13 through Day 1 of Week 25 during the treatment period. The CSF samples will be analyzed for CSF Aβ42/40 ratio, total tau (T-tau) protein concentration, phosphorylated tau (P-tau) protein concentration, and other relevant biomarkers.The final test indicators shall prevail.	25 weeks
Change in albumin levels in blood and cerebrospinal fluid (CSF) from pre-treatment to post-treatment	All participants shall provide blood and cerebrospinal fluid (CSF) samples for albumin level testing at the following time points: prior to the first dose, 4 h ± 0.5 h after completion of the 5th dose (Week 13 Day 1), 4 h ± 0.5 h after completion of the 9th dose (Week 25 Day 1), and at the time of CSF collection during the treatment period. If CSF collection is scheduled at Week 13 or Week 25, the blood samples intended for albumin level testing at Week 13 or Week 25 may be collected prior to CSF sampling without duplicate blood draws; such blood samples shall also be obtained after dosing at the respective visit, with collection timing kept as close to the CSF draw as possible.	25 weeks
Change in albumin quality in blood and cerebrospinal fluid (CSF) from pre-treatment to post-treatment	All participants shall provide blood and cerebrospinal fluid (CSF) samples for albumin quality testing at the following time points: prior to the first dose, 4 h ± 0.5 h after completion of the 5th dose (Week 13 Day 1), 4 h ± 0.5 h after completion of the 9th dose (Week 25 Day 1), and at the time of CSF collection during the treatment period. If CSF collection is scheduled at Week 13 or Week 25, the blood samples required for albumin quality testing at these time points may be drawn prior to CSF sampling without duplicate blood draws. Such blood samples shall also be collected after dosing at the respective visit, with sampling timing kept as close to CSF collection as possible. Testing items for albumin quality in blood and CSF shall cover free thiol levels, sulfinylation levels, carbonylation levels, glycation levels, homocysteinylation levels, and other relevant indicators.The final test indicators shall prevail.	25 weeks

Collaborators and Investigators

• Sponsor: Protgen Ltd
• Investigators: Study Director: Xia Li, Ph.D, Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2024
• Primary Completion (Actual): April 14, 2026
• Study Completion (Actual): April 14, 2026

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 3, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; recombinant human serum albumin-heme
• Other Study ID Numbers: rHSA2024-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No