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[1].
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[2][3].
| 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 |
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:
Antioxidant activity: HSA binds free radicals, metal ions (copper, iron), and toxic metabolites, reducing oxidative stress in the vasculature and brain[4].
Blood-brain barrier (BBB) support: Albumin is a key component of the neurovascular unit. It maintains endothelial integrity and supports the perivascular clearance system that removes amyloid-beta from the brain parenchyma via the glymphatic system[5].
Anti-inflammatory effects: Albumin binds pro-inflammatory lipids and cytokines, modulating systemic and CNS inflammation — a key driver of neuroinflammation in Alzheimer's disease.
Drug carrier properties: Albumin's exceptional binding capacity for various molecules makes it an ideal carrier for therapeutic agents, and it has been explored as a platform for CNS drug delivery[6].
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[2:1].
BBB dysfunction in AD: AD is characterized by progressive breakdown of the blood-brain barrier, with loss of perivascular clearance leading to amyloid-beta and tau protein accumulation in the brain[7].
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[3:1].
Oxidative stress reduction: The antioxidant capacity of albumin may help counteract the elevated oxidative stress observed in AD brains.
Intravenous administration of recombinant human serum albumin (rHSA) may:
Participants are randomized to receive one of three dose levels of recombinant human serum albumin injection:
The randomization ratio is 1:1:1 across the three arms. The trial is open-label (participants and investigators know the assigned dose), which is appropriate for early-phase exploratory safety studies.
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.
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 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 |
As an early-phase trial, comprehensive safety monitoring is integrated throughout the treatment period:
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 |
The blood-brain barrier (BBB) is progressively compromised in Alzheimer's disease, contributing to the accumulation of amyloid-beta in brain tissue[7:1]. 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[5:1][3:2]:
Low serum albumin (hypoalbuminemia) is associated with worse outcomes in multiple neurological conditions. Epidemiological studies have shown:
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.
NCT06489015 represents an early but scientifically grounded exploration of serum albumin as a disease-modifying strategy for Alzheimer's disease. While the intervention is not disease-specific in the way monoclonal antibodies targeting amyloid-beta or tau 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:
Schrater KF, et al. Recombinant human serum albumin: pharmaceutical properties and therapeutic potential. Biotechnology and Bioengineering. 2021. ↩︎
Ashford JW, et al. Serum albumin and cognitive function in aging and Alzheimer's disease. Journal of Alzheimer's Disease. 2021. ↩︎ ↩︎ ↩︎
Cilliers K, et al. Blood-brain barrier dysfunction in Alzheimer's disease: albumin as a therapeutic target. Acta Neuropathologica. 2024. ↩︎ ↩︎ ↩︎
Morganti S, et al. The role of serum albumin in modulating neuroinflammation: therapeutic implications for Alzheimer's disease. Frontiers in Neuroscience. 2022. ↩︎ ↩︎
Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta Neuropathologica. 2019. ↩︎ ↩︎
Kern R, et al. Human serum albumin as a versatile carrier for therapeutic proteins. Advanced Drug Delivery Reviews. 2017. ↩︎
Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer's disease. Nature Reviews Neuroscience. 2011. ↩︎ ↩︎