Recombinant Human Serum Albumin for Alzheimer's Disease (NCT06489015)

Recombinant Human Serum Albumin for Alzheimer's Disease (NCT06489015)

Overview

NCT06489015 is an open-label, parallel-group exploratory Phase 1 clinical trial evaluating the safety and preliminary efficacy of recombinant human serum albumin (rHSA) injection in the treatment of mild-to-moderate Alzheimer's disease (AD). The trial is sponsored by Protgen Ltd and is being conducted across five hospital sites in China["@schrater2021"].

This trial represents an exploratory investigation into whether intravenous serum albumin — a protein with multiple neuroprotective properties including antioxidant activity, blood-brain barrier support, and anti-inflammatory effects — can provide clinical benefit in AD patients["@ashford2021"][@cilliers2024].

Recombinant Human Serum Albumin for Alzheimer's Disease (NCT06489015)

Overview

NCT06489015 is an open-label, parallel-group exploratory Phase 1 clinical trial evaluating the safety and preliminary efficacy of recombinant human serum albumin (rHSA) injection in the treatment of mild-to-moderate Alzheimer's disease (AD). The trial is sponsored by Protgen Ltd and is being conducted across five hospital sites in China["@schrater2021"].

This trial represents an exploratory investigation into whether intravenous serum albumin — a protein with multiple neuroprotective properties including antioxidant activity, blood-brain barrier support, and anti-inflammatory effects — can provide clinical benefit in AD patients["@ashford2021"][@cilliers2024].

Trial Details

| Attribute | Value |
|-----------|-------|
| NCT Number | NCT06489015 |
| Phase | Early Phase 1 |
| Status | Active, not recruiting (Verified March 2026) |
| Sponsor | Protgen Ltd |
| Intervention | Recombinant Human Serum Albumin (rHSA) |
| Participants | 30 (estimated) |
| Design | Open-label, parallel-group, randomized 1:1:1 (20g / 30g / 40g) |
| Duration | 25 weeks treatment |
| Sites | 5 hospitals across China |
| ClinicalTrials.gov | [View Trial](https://clinicaltrials.gov/study/NCT06489015) |

Mechanism of Action

Serum Albumin Biology

Human serum albumin (HSA) is the most abundant plasma protein (~40-50 g/L in blood) with multiple critical functions relevant to [Alzheimer's disease](/diseases/alzheimers-disease):

Albumin and Neurodegeneration

Several lines of evidence support the investigation of albumin in AD:

• Serum albumin decline with aging: Plasma albumin levels decrease with age, and lower serum albumin is associated with worse cognitive outcomes and increased AD risk[@ashford2021].
• BBB dysfunction in AD: AD is characterized by progressive breakdown of the blood-brain barrier, with loss of perivascular clearance leading to [amyloid-beta](/proteins/amyloid-beta) and [tau protein](/proteins/tau-protein) accumulation in the brain[@zlokovic2011].
• Neurovascular unit impairment: The neurovascular unit — comprising endothelial cells, pericytes, astrocytes, and neurons — progressively deteriorates in AD. Albumin helps maintain the structural and functional integrity of this system[@cilliers2024].
• Oxidative stress reduction: The antioxidant capacity of albumin may help counteract the elevated oxidative stress observed in AD brains.

Rationale for rHSA in AD

Intravenous administration of recombinant human serum albumin (rHSA) may:

• Boost plasma antioxidant capacity
• Support BBB integrity and perivascular clearance
• Reduce peripheral and CNS inflammatory burden
• Restore albumin-mediated transport of neurotoxic metabolites away from the brain

Study Design

Intervention Details

Participants are randomized to receive one of three dose levels of recombinant human serum albumin injection:

• Low dose: 20g per administration
• Medium dose: 30g per administration
• High dose: 40g per administration

Treatment Schedule

Based on the trial duration of 25 weeks, participants receive intravenous rHSA infusions on a schedule to be determined (frequency unspecified in available protocol data). The extended 25-week treatment period allows for assessment of both safety and preliminary efficacy signals over a meaningful timeframe.

Eligibility Criteria

Inclusion Criteria

• Adults aged 50-85 years
• Clinical diagnosis of mild to moderate Alzheimer's disease
• Meets NIA-AA criteria for probable AD
• Clinical Dementia Rating — Global Score (CDR-GS) ≤ 2 (indicating mild or moderate dementia)
• Stable baseline medication regimen
• Capable of providing informed consent (or with legal guardian/caregiver consent)

Exclusion Criteria

• Other primary causes of dementia (e.g., [vascular dementia](/diseases/vascular-dementia), [Lewy body dementia](/diseases/dementia-lewy-bodies), frontotemporal dementia)
• Severe cardiovascular disorders (uncontrolled heart failure, recent myocardial infarction, severe arrhythmia)
• Severe metabolic disorders (uncontrolled diabetes, severe liver or kidney disease)
• Active hepatitis B, hepatitis C, or HIV infection
• History of hypersensitivity to plasma-derived products
• Recent use of plasma derivatives or albumin-based therapeutics
• Active malignancy or history of malignancy within 5 years
• Participation in another clinical trial within 30 days
• Significant psychiatric comorbidities that could interfere with assessment

Endpoints

Primary Endpoint

Change in ADAS-Cog (Alzheimer's Disease Assessment Scale — Cognitive subscale) score from baseline to Week 25 post-treatment initiation.

The ADAS-Cog is the gold-standard cognitive assessment tool for AD clinical trials, measuring memory, language, praxis, and orientation. A lower score indicates better cognitive function.

Secondary Endpoints

Secondary efficacy assessments at weeks 7, 16, and 25 include:

| Measure | Full Name | Description |
|---------|-----------|-------------|
| ADAS-Cog | Alzheimer's Disease Assessment Scale — Cognitive | Repeat cognitive assessment at intermediate timepoints |
| CDR-GS | Clinical Dementia Rating — Global Score | Global dementia severity staging |
| NPI | Neuropsychiatric Inventory | Assessment of behavioral and psychological symptoms in dementia |
| ADCS-ADL | Alzheimer's Disease Cooperative Study — Activities of Daily Living | Functional independence assessment |

Safety Monitoring

As an early-phase trial, comprehensive safety monitoring is integrated throughout the treatment period:

• Adverse event recording and grading
• Laboratory assessments (hematology, chemistry, liver/renal function)
• Vital signs and physical examinations
• Immunogenicity testing (antibody formation against rHSA)

Study Sites

The trial is conducted across five hospital sites in China:

| Site | City | Province/Municipality |
|------|------|----------------------|
| Luoyang Third People's Hospital | Luoyang | Henan |
| The First Affiliated Hospital of Zhengzhou University | Zhengzhou | Henan |
| Wuhan Union Hospital of China | Wuhan | Hubei |
| Clinical Medical College & Affiliated Hospital of Jiujiang University | Jiujiang | Jiangxi |
| Shanghai Mental Health Center | Shanghai | Shanghai Municipality |

Scientific Context

Albumin and the Blood-Brain Barrier in AD

The blood-brain barrier (BBB) is progressively compromised in [Alzheimer's disease](/diseases/alzheimers-disease), contributing to the accumulation of [amyloid-beta](/proteins/amyloid-beta) in brain tissue[@zlokovic2011]. The glymphatic system — a perivascular waste clearance pathway dependent on astroglial AQP4 water channels — relies on intact neurovascular structures to function effectively. Albumin helps maintain this system through multiple mechanisms[@bell2019][@cilliers2024]:

• Preservation of endothelial tight junctions
• Support of pericyte function
• Modulation of astrocyte end-foot expression of AQP4
• Binding and clearance of neurotoxic proteins from the perivascular space

Hypoalbuminemia in Aging and Neurodegeneration

Low serum albumin (hypoalbuminemia) is associated with worse outcomes in multiple neurological conditions. Epidemiological studies have shown:

• Lower serum albumin correlates with faster cognitive decline in AD[@ashford2021]
• Hypoalbuminemia predicts greater atrophy in AD-sensitive brain regions
• Albumin supplementation in animal models reduces neuroinflammation and improves cognitive performance[@morganti2022]

Previous Albumin Trials in Neurodegeneration

Intravenous immunoglobulin (IVIG) — which contains pooled human antibodies including albumin — has been tested in AD trials with mixed results. These trials demonstrated that albumin-enriched blood products have a favorable safety profile in elderly populations, providing support for the safety hypothesis of this trial.

Significance and Outlook

NCT06489015 represents an early but scientifically grounded exploration of serum albumin as a disease-modifying strategy for [Alzheimer's disease](/diseases/alzheimers-disease). While the intervention is not disease-specific in the way monoclonal antibodies targeting [amyloid-beta](/proteins/amyloid-beta) or [tau](/proteins/tau-protein) are, it addresses foundational neurovascular and neuroinflammatory mechanisms that may complement or synergize with other therapeutic approaches.

The trial's focus on safety and preliminary efficacy in an early-phase design allows for dose-finding and signal detection before larger phase 2 or 3 trials. The three-dose design provides important dose-response data that will inform future development.

Key questions this trial will begin to address:

• Is intravenous rHSA safe in AD patients over a 25-week period?
• Is there a dose-response relationship for cognitive outcomes?
• Does rHSA treatment reduce biomarkers of neuroinflammation or BBB dysfunction?
• Which dose level offers the best balance of safety and preliminary efficacy?

Related Pages

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Neuroinflammation in Alzheimer's Disease](/mechanisms/neuroinflammation-ad)
• [Amyloid-Beta Protein](/proteins/amyloid-beta)
• [Tau Protein](/proteins/tau-protein)
• [Blood-Brain Barrier in Neurodegeneration](/mechanisms/blood-brain-barrier-ad)
• [Alzheimer's Disease Clinical Trials Index](/clinical-trials/alzheimers-disease)

External Links

• [ClinicalTrials.gov — NCT06489015](https://clinicaltrials.gov/study/NCT06489015)
• [Protgen Ltd](https://www.protgen.com) (sponsor website)