Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)

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title: "Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)"
description: Phase 1 open-label study of recombinant human serum albumin for mild to moderate Alzheimer disease
published: true
tags: section:clinical-trials, kind:clinical-trial, topic:alzheimers, state:published
editor: markdown

Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)

Study Overview

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NCT Number: NCT06489015

Official Title: Phase 1 Open-label, Exploratory Study of Recombinant Human Serum Albumin (rHSA) for Mild to Moderate Alzheimer's Disease

Study Type: Interventional (Phase 1)

Status: Recruiting

Study Start Date: June 2024

Estimated Enrollment: 30 participants

Background and Rationale

...

Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)

Study Overview

Mermaid diagram (expand to render)

NCT Number: NCT06489015

Official Title: Phase 1 Open-label, Exploratory Study of Recombinant Human Serum Albumin (rHSA) for Mild to Moderate Alzheimer's Disease

Study Type: Interventional (Phase 1)

Status: Recruiting

Study Start Date: June 2024

Estimated Enrollment: 30 participants

Background and Rationale

Human serum albumin is the most abundant plasma protein in the human body and plays multiple protective roles in systemic and brain health. Albumin binds and transports a wide variety of molecules, including:

Fatty acids: Essential for neuronal energy metabolism
Bilirubin: Potent endogenous antioxidant
Drugs and hormones: Carrier for therapeutic compounds
Metals: Binds copper, zinc, and other transition metals

In Alzheimer's disease, several lines of evidence suggest albumin may be beneficial:

Oxidative stress reduction: Albumin's bilirubin-binding capacity provides antioxidant protection against lipid peroxidation

Metal ion chelation: Albumin binds redox-active metals (copper, iron) that catalyze Aβ aggregation and oxidative damage

Aβ binding: Human serum albumin can bind amyloid-beta, potentially reducing its aggregation and toxicity

Blood-brain barrier transport: Albumin-mediated transport may facilitate drug delivery to the CNS

Inflammation modulation: Albumin has anti-inflammatory properties through multiple mechanisms

The concept of using albumin as a therapeutic agent for AD is supported by:

Observational studies showing lower serum albumin levels correlate with cognitive decline in AD
Albumin replacement studies in other conditions showing neurological benefits
Preclinical evidence of albumin-mediated neuroprotection

Study Objectives

Primary Objective

To evaluate the safety and tolerability of recombinant human serum albumin (rHSA) in patients with mild to moderate Alzheimer's disease.

Secondary Objectives

To assess the pharmacokinetics of rHSA in AD patients

To explore preliminary efficacy through cognitive assessments

To measure changes in AD biomarkers (CSF Aβ, tau, NfL)

To evaluate patient-reported outcomes and quality of life

Methods

Study Design

Design: Single-arm, open-label, Phase 1 study
Participants: 30 patients with mild to moderate AD (MMSE 12-26)
Duration: 12-week treatment period with 4-week follow-up

Inclusion Criteria

Age 50-85 years
Diagnosis of probable AD (NIA-AA criteria)
MMSE score 12-26 (mild to moderate dementia)
Stable on AD medications (cholinesterase inhibitors, memantine) for ≥3 months
Normal or stable medical conditions

Exclusion Criteria

Other causes of dementia (vascular, Lewy body, frontotemporal)
Active inflammatory or infectious disease
Chronic liver disease (albumin synthesis impairment)
Chronic kidney disease (albumin loss)
Planned surgeries during study period

Treatment Regimen

| Parameter | Details |
|-----------|---------|
| Drug | Recombinant Human Serum Albumin (rHSA) |
| Dose | 1.5 g/kg (approximately 100g for average adult) |
| Route | Intravenous infusion |
| Frequency | Weekly infusions |
| Duration | 12 weeks (12 infusions total) |

Outcome Measures

Safety (Primary):

Adverse event monitoring
Vital signs
Laboratory parameters (CBC, CMP, coagulation)
Physical and neurological examinations

Efficacy (Secondary):

Cognitive: ADAS-Cog13, MMSE, MoCA
Functional: ADCS-ADL, CDR
Behavioral: NPI, Neuropsychiatric Inventory
Quality of Life: EQ-5D-5L

Biomarkers:

CSF Aβ40, Aβ42, total tau, phosphorylated tau
Plasma NfL, GFAP
Serum albumin levels and albumin/globulin ratio

Scientific Rationale

Albumin-Aβ Interaction

Human serum albumin has been shown to:

Bind Aβ monomers with moderate affinity
Prevent Aβ fibril formation in vitro
Reduce Aβ-induced neurotoxicity in cell culture
Facilitate Aβ clearance through multiple mechanisms

Antioxidant Effects

Albumin's capacity to bind bilirubin makes it an important endogenous antioxidant:

Bilirubin-albumin complexes neutralize reactive oxygen species
Prevents lipid peroxidation in neuronal membranes
May reduce 4-HNE and MDA levels in AD brain

Metal Chelation

Albumin's metal-binding properties may reduce redox-active metal catalysis of Aβ aggregation:

Binds Cu²⁺ and Fe³⁺ with micromolar affinity
Prevents metal-induced Aβ aggregation
May reduce Fenton chemistry and oxidative damage

Relationship to Existing Knowledge

This trial connects to established mechanisms:

[Amyloid-Beta Metabolism and Clearance](/mechanisms/amyloid-beta-metabolism)
[Oxidative Stress in Alzheimer's](/mechanisms/oxidative-stress-ad)
[Blood-Brain Barrier and CNS Drug Delivery](/mechanisms/bbb-dysfunction-pathway)
[Metal Ion Dyshomeostasis in Neurodegeneration](/mechanisms/metal-ion-dyshomeostasis)

Expected Outcomes

Safety profile: Characterize tolerability of weekly rHSA infusions in AD patients

Biomarker trends: Identify changes in CSF and plasma AD biomarkers

Proof-of-concept: Establish preliminary efficacy signal to guide Phase 2 studies

Dosing optimization: Determine optimal dose and administration schedule

Clinical Significance

If successful, rHSA therapy could provide:

Novel mechanism: First-in-class approach targeting multiple pathways (Aβ, oxidative stress, metal dyshomeostasis)
Accessibility: Well-characterized protein with established safety profile
Combination potential: Could be combined with existing AD therapies
Disease modification: Potential to address underlying pathophysiology

Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)

Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)

Study Overview

Background and Rationale

Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)

Study Overview

Background and Rationale

Study Objectives

Primary Objective

Secondary Objectives

Methods

Study Design

Inclusion Criteria

Exclusion Criteria

Treatment Regimen

Outcome Measures

Scientific Rationale

Albumin-Aβ Interaction

Antioxidant Effects

Metal Chelation

Relationship to Existing Knowledge

Expected Outcomes

Clinical Significance

See Also