Overview
Mermaid diagram (expand to render)
AMDX-2011P is a novel retinal amyloid tracer being developed by Amydis Inc. for the non-invasive detection of amyloid deposits in the retina of [Alzheimer's disease](/diseases/alzheimers-disease) patients. This Phase 2 clinical trial evaluates the safety, tolerability, pharmacokinetics, and biological activity of AMDX-2011P as a potential diagnostic tool for Alzheimer's disease.
Trial Details
| Parameter | Value |
|-----------|-------|
| NCT Number | NCT06514001 |
| Status | RECRUITING (as of February 2026) |
| Phase | Phase 2 |
| Sponsor | Amydis Inc. |
| Intervention | AMDX-2011P 100 mg single bolus intravenous injection |
| Enrollment | 25 participants (estimated) |
| Study Design | Open-label, single-dose |
Study Objectives
Primary Objective
- Evaluate the safety and tolerability of AMDX-2011P in participants with Alzheimer's disease
- Assess the incidence and severity of adverse events over 8 days following administration
Secondary Objectives
- Characterize plasma pharmacokinetics (Cmax, AUC over 2 hours)
- Evaluate biological activity of AMDX-2011P as a retinal tracer
- Assess detection of retinal amyloid deposits at 8 days post-administration
Eligibility Criteria
Key Inclusion Criteria
Confirmed diagnosis of Alzheimer's disease
Positive amyloid beta PET scan indicating presence of amyloid pathology
Willingness to undergo [APOE](/proteins/apoe) genotyping
Ability to fixate and complete retinal imaging proceduresKey Exclusion Criteria
Glaucoma or suspected glaucoma
Age-related macular degeneration (AMD)
Clinically significant laboratory abnormalities
Prolonged QTcF interval
Cardiac arrhythmia or significant ECG abnormalitiesStudy Design
This is a Phase 2, open-label, single-dose study conducted at a single site:
- Site: Associated Retina Consultants, Phoenix, Arizona, USA
- Contact: Matthew Lehman (info@amydis.com, 859-905-0402)
- Duration: 8-day observation period per participant
Mechanism of Action
AMDX-2011P is designed as a retinal amyloid tracer that:
Binds to retinal amyloid deposits — The compound selectively binds to [amyloid-beta](/proteins/amyloid-beta) aggregates that accumulate in the retina of AD patients
Enables non-invasive imaging — Unlike PET imaging which requires brain scanning, retinal imaging is less invasive and more accessible
Provides amyloid detection — The tracer allows visualization and quantification of amyloid burden in the retinaRationale for Retinal Amyloid Imaging
The retina offers several advantages for Alzheimer's disease biomarker detection:
Direct visualization — The retina is an accessible part of the CNS that can be imaged non-invasively
Correlation with brain pathology — Retinal amyloid deposits correlate with cerebral amyloid burden
Earlier detection — Retinal changes may occur earlier than detectable brain changes
Repeated monitoring — Allows for easy repeated assessments over timeSignificance for Alzheimer's Disease
This trial represents an important step in Alzheimer's disease diagnostics because:
Non-invasive alternative — Provides an alternative to PET imaging which is expensive and involves radiation exposure
Accessibility — Retinal imaging could be performed in outpatient settings
Trial enrichment — Could help identify patients with amyloid pathology for clinical trials
Disease monitoring — Potential for tracking disease progression and treatment responseAmyloid Biology Context
Amyloid-beta (Aβ) deposition is a hallmark pathological feature of Alzheimer's disease:
- [Amyloid Beta Peptide](/concepts/amyloid-beta-peptide) — The key protein fragment that aggregates into plaques
- [Amyloid Cascade Hypothesis](/mechanisms/amyloid-cascade-hypothesis) — The leading theoretical framework for AD pathogenesis
Related Pages
- [Retinal Imaging in Neurodegeneration](/diagnostics/retinal-imaging)
- [Optical Coherence Tomography in Neurodegeneration](/diagnostics/optical-coherence-tomography)
- [Amyloid PET Imaging](/diagnostics/pet-imaging) — Current standard for amyloid detection
- [APOE Genotyping for Neurodegenerative Disease Risk Assessment](/diagnostics/apoe-genotyping)
- [CSF Biomarkers in Neurodegeneration](/diagnostics/csf-biomarkers)
- [Plasma Biomarkers in Neurodegeneration](/diagnostics/plasma-biomarkers)
- [P-tau 217](/biomarkers/p-tau-217) — Other emerging AD biomarker
- [Clinical Trials Overview](/clinical-trials) — Index of all clinical trials
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Amydis Inc.](/organizations/amydis-inc)
Amyydis Inc. - Company Background
Company Overview
Amydis Inc. is a privately held biotechnology company founded in 2014 with a focus on developing non-invasive diagnostics for neurodegenerative diseases. The company's lead program targets retinal amyloid detection as a biomarker for Alzheimer's disease.
Retinal Amyloid Detection:
- Proprietary fluorescent compounds that bind to amyloid deposits
- Designed for visualization via standard retinal imaging devices
- Non-invasive alternative to PET imaging
- Potentially lower cost than brain PET
Pipeline Programs:
- AMDX-2011P: Lead candidate for Alzheimer's disease (Phase 2)
- Early-stage programs for other neurodegenerative conditions
- Potential companion diagnostics for therapeutic development
Funding and Partnerships
- Raised Series A funding in 2016
- Received NIH grants for Alzheimer's diagnostic development
- Strategic partnership discussions ongoing
- Investigator-initiated trials at academic centers
Amyloid Biology and Retinal Deposition
Amyloid-Beta in Alzheimer's Disease Pathogenesis
The amyloid-beta peptide is central to Alzheimer's disease pathology:
APP Processing:
- Amyloid precursor protein (APP) is a transmembrane protein
- Beta-secretase (BACE1) cleaves APP to generate C99 fragment
- Gamma-secretase cleaves C99 to release amyloid-beta peptides
- Aβ40 and Aβ42 are most common species
Aβ Aggregation:
- Aβ42 is more aggregation-prone than Aβ40
- Forms soluble oligomers, then fibrils, then plaques
- Oligomers are considered most toxic
- Plaques are pathological hallmark but may be protective
Amyloid Cascade Hypothesis:
- Aβ accumulation is the initiating event
- Leads to tau pathology, neurodegeneration, cognitive decline
- Supported by genetic evidence (APP, PSEN1, PSEN2 mutations)
- Therapeutic targeting of Aβ has had mixed results
Retinal Amyloid Deposition
Evidence for Retinal Aβ:
- Retinal amyloid deposits documented in AD patients
- Correlate with brain amyloid burden on PET
- May precede cognitive symptoms
- Detectable via specialized imaging
Advantages of Retinal Detection:
- Direct access to CNS tissue (retina is brain-derived)
- Non-invasive imaging possible
- High resolution imaging available
- May allow earlier detection than brain imaging
Challenges:
- Quantification methods still developing
- Correlation with brain amyloid not perfect
- Standardization of imaging protocols needed
- Sensitivity compared to PET still being established
Study Design and Methodology
Phase 2 Study Design
NCT06514001 Details:
- Single-center, open-label study
- Single ascending dose design
- 25 participants with confirmed AD
- 8-day observation period
Study Phases:
Screening (Day -28 to -1):
- Confirm AD diagnosis
- Verify positive amyloid PET
- Complete baseline assessments
- Obtain informed consent
- Safety laboratory evaluation
- APOE genotyping
Baseline (Day -7):
- Complete physical examination
- Baseline retinal imaging (pre-dose)
- Vital signs and ECG
- Confirm eligibility
Dosing (Day 1):
- Administer AMDX-2011P (100 mg IV)
- Monitor vital signs
- Collect PK samples
- Observe for acute reactions
Observation (Days 1-8):
- Daily vital signs
- Adverse event monitoring
- Retinal imaging at Day 8
- PK sampling schedule
Follow-up (Day 14, Day 28):
- Safety assessment
- Final study visit
Imaging Protocol
Retinal Imaging Methods:
- Fundus photography
- Optical coherence tomography (OCT)
- Confocal scanning laser ophthalmoscopy (cSLO)
- Adaptive optics (research settings)
Imaging Timepoints:
- Pre-dose baseline
- Day 8 post-dose (primary endpoint)
- Safety follow-up imaging
Image Analysis:
- Semi-quantitative amyloid detection
- Comparison to baseline
- Central reading by qualified ophthalmologist
Pharmacokinetic Sampling
PK Parameters to Evaluate:
- Cmax (maximum concentration)
- AUC (area under curve)
- Tmax (time to maximum)
- Half-life
- Clearance
Sample Collection:
- Blood samples at multiple timepoints
- Plasma separation within 30 minutes
- Storage at -80°C
- Bioanalysis by validated LC-MS/MS
Safety and Tolerability Assessment
Safety Endpoints
Primary Safety Variables:
- Incidence of adverse events (AEs)
- Serious adverse events (SAEs)
- Changes in vital signs
- Laboratory abnormalities
- ECG changes
- Ocular examination findings
Adverse Event Classification:
- Severity (mild, moderate, severe)
- Relationship to study drug (unrelated, possibly related, probably related, definitely related)
- Expected vs. unexpected
- Serious vs. non-serious
Expected Adverse Events
Based on Compound Class:
- Injection site reactions (mild)
- Headache
- Nausea
- Transient visual changes
- Hypersensitivity reactions (rare)
Monitoring Plan:
- Continuous vital sign monitoring
- Pre- and post-dose ophthalmologic exams
- Daily safety laboratory evaluation
- Full physical examination at end of study
Safety Stopping Rules
Criteria for Study Interruption:
- More than 2 participants with drug-related severe AEs
- Any drug-related SAE
- Clinically significant laboratory abnormality
- Ocular safety signals
Biological Activity and Validation
Retinal Amyloid Detection
Detection Method:
- Fluorescent signal from bound compound
- Quantification of signal intensity
- Comparison to established thresholds
- Correlation with PET amyloid burden
Expected Findings:
- Detectable signal in amyloid-positive retinas
- Minimal signal in controls
- Dose-response relationship
- Correlation with PET SUVR
Amyloid PET Correlation
PET Imaging Standard:
- Standardized Uptake Value Ratio (SUVR)
- Centiloid scale for standardization
- Posterior cingulate/precuneus region
- Threshold: Centiloid >20 considered positive
Correlation Analysis:
- Compare retinal signal to PET SUVR
- Evaluate sensitivity and specificity
- Assess predictive value
- Determine optimal detection threshold
Biomarker Validation
Biomarker Qualification:
- Analytical validation of detection method
- Clinical validation in target population
- Correlation with clinical endpoints
- Establishment of reference ranges
Diagnostic Significance
Alzheimer's Disease Diagnostics Landscape
Current Diagnostic Challenges:
- Definitive diagnosis requires brain autopsy
- Clinical diagnosis has limited sensitivity/specificity
- Biomarkers improving but accessibility issues
- Need for early, accessible detection methods
Available Biomarker Tests:
- CSF Aβ42/tau ratio (invasive, specialized)
- Plasma Aβ and p-tau (emerging, accessible)
- Amyloid PET (expensive, radiation, limited access)
- FDG-PET for neurodegeneration
- Structural MRI for atrophy
Role of Retinal Imaging
Potential Advantages:
- Non-invasive (vs. LP for CSF)
- No radiation (vs. PET)
- Lower cost potential
- Accessible in ophthalmology settings
- Repeatable for monitoring
Limitations:
- Less established than PET
- Technical challenges in quantification
- Not yet validated for clinical use
- Requires specialized expertise
Clinical Utility
Potential Applications:
Screening: Identify individuals needing confirmatory testing
Diagnosis support: Add evidence for clinical diagnosis
Monitoring: Track amyloid burden over time
Therapeutic monitoring: Assess treatment response
Research enrichment: Identify amyloid-positive for trialsImplementation Considerations:
- Required imaging expertise
- Equipment availability
- Training for interpretation
- Standardized protocols
- Quality assurance
Future Development Plans
Phase 3 Registration Trial
Design Considerations:
- Larger sample size (hundreds to thousands)
- Multi-center international study
- Confirm sensitivity and specificity
- Compare to standard of care
- Regulatory submissions
Endpoints:
- Diagnostic accuracy (sensitivity, specificity)
- Positive/negative predictive values
- Inter-reader reliability
- Safety in broader population
Companion Diagnostic Potential
Therapeutic Development Integration:
- Patient selection for anti-amyloid trials
- Treatment response monitoring
- Safety monitoring for amyloid-related effects
- Combination with therapeutic candidates
Pharmaceutical Partnerships:
- CRO partnerships for large-scale studies
- Pharma collaboration for trial enrollment
- Diagnostic-therapeutic co-development
- Regulatory strategy alignment
Broader Applications
Other Neurodegenerative Diseases:
- Parkinson's disease (alpha-synuclein in retina)
- Dementia with Lewy bodies
- Vascular dementia
- Frontotemporal dementia
- Amyotrophic lateral sclerosis
Screening Applications:
- At-risk population screening
- Population-based testing
- Primary care integration
- Teleophthalmology potential
Regulatory Considerations
FDA Pathway
Diagnostic Device Classification:
- Class II medical device (if cleared)
- Requires 510(k) or De Novo submission
- Predicate device needed (or novel pathway)
- Clinical performance data required
Development Pathway:
- Breakthrough Device designation (potential)
- Parallel review with FDA and CMS
- Collaboration with professional societies
- Coverage determination discussions
Reimbursement Strategy
Medicare Coverage:
- LCD (Local Coverage Determination) process
- LCDD (Laboratory) vs. diagnostic imaging
- Evidence development pathway
- Clinical utility demonstration needed
Private Payers:
- Medical necessity documentation
- CPT code development
- Reasonable and customary rates
- Prior authorization processes
Competitive Analysis
Other Retinal Diagnostics
| Company | Product | Target | Development Stage |
|---------|---------|--------|-------------------|
| Amydis | AMDX-2011P | Amyloid | Phase 2 |
| Cognoptix | Sapphire II | Amyloid | Research |
| Neurovision | Retinal imaging | Amyloid | Research |
| Neurodegeneration | Various | Tau, alpha-syn | Early |
Comparison to PET
Advantages over Amyloid PET:
- Lower cost (~$100 vs. ~$3000)
- No radiation exposure
- Faster (minutes vs. hours)
- More accessible
- Repeatable
Disadvantages vs. Amyloid PET:
- Less established
- Limited validation data
- May have lower sensitivity
- Technical expertise required
Molecular Imaging Mechanism
Fluorescence Detection Technology
AMDX-2011P utilizesfluorescence imaging to detect retinal amyloid deposits following intravenous administration:
Fluorescence Properties:
- Excitation wavelength: Optimized for retinal imaging devices
- Emission wavelength: Near-infrared for enhanced tissue penetration
- Quantum yield: High brightness for sensitive detection
- Photostability: Stable signal during imaging acquisition
Imaging Acquisition:
Baseline fundus photography prior to tracer administration
Day 8 post-administration imaging session
Semi-quantitative fluorescence analysis
Comparison with established retinal imaging biomarkersAmyloid Binding Kinetics
The binding characteristics of AMDX-2011P determine detection sensitivity:
Association Kinetics:
- Rapid binding to amyloid aggregates
- High affinity (nanomolar Kd range)
- Slow off-rate for stable signal
- Preference for oligomeric and fibrillar species
Selectivity Profile:
- High selectivity for Aβ aggregates over monomers
- Minimal binding to other retinal proteins
- No significant lipofuscin interaction
- Preserved specificity in degenerating retina
Correlation with Brain Amyloid
The retinal amyloid burden correlates with cerebral pathology:
Cross-Sectional Correlation:
- Retinal Aβ correlates with PET amyloid burden
- Correlations strongest in mild-moderate disease stages
- Retinal imaging may reflect global brain amyloid load
- Regional specificity being investigated
Temporal Relationship:
- Retinal changes may precede brain changes in some cases
- Parallel disease progression in retina and brain
- Potential for earlier detection via retina
Clinical Validation Pathway
Regulatory Considerations
The development pathway addresses regulatory requirements:
Diagnostic Device Classification:
- Combination drug-device product
- Requires both drug and device clearance
- Companion diagnostic framework
- Biomarker validation requirements
Clinical Utility Requirements:
- Demonstration of clinical impact
- Integration with standard of care
- Reimbursement pathway
- Clinical decision support utility
Comparison with Other Retinal Approaches
| Feature | AMDX-2011P | Structural OCT | Functional Testing |
|---------|-------------|---------------|--------------------|
| Target | Amyloid-specific | Structure | Function |
| Specificity | High (Aβ) | Moderate | Low |
| Disease specificity | High | Moderate | Low |
| Implementation | Medium | Low | Low |
| Regulatory status | Investigational | Approved | Approved |
Market Potential
Target Population:
- 6 million AD patients in US
- 55 million globally
- Early detection priority population
- Clinical trial enrichment
Competitive Advantages:
- Non-invasive detection alternative
- Reduced healthcare costs
- Population-wide screening potential
- Primary care implementation
Implementation Considerations
Healthcare System Integration:
- Ophthalmology practice settings
- Neurology referral pathways
- Primary care screening programs
- Clinical trial sites
Cost-Effectiveness:
- Reduced compared to PET imaging
- Population screening feasibility
- Early intervention enablement
- Care pathway optimization
Technical Specifications
AMDX-2011P Formulation:
- Concentration: 100 mg single bolus
- Route: Intravenous injection
- Volume: 10 mL
- Vehicle: Sterile saline
Imaging System Requirements
Compatible Devices:
- Confocal scanning laser ophthalmoscopy (cSLO)
- Fundus camera with fluorescence capability
- Specialized retinal amyloid imaging systems
- Adaptive optics systems (research)
Image Analysis:
- Semi-quantitative scoring
- Quantitative fluorescence measurement
- Machine learning analysis
- Automated detection algorithms
Research Gaps and Future Directions
Unresolved Questions
Scientific Questions:
What is the exact composition of retinal amyloid?
How does retinal amyloid differ from brain amyloid?
What drives amyloid deposition in retina?
Can retinal amyloid be cleared therapeutically?Clinical Questions:
Will retina-based detection replace PET?
How often should screening occur?
What is the prognostic value?
Can treatment response be monitored?Planned Studies
Future Clinical Development:
| Study | Phase | Timeline | Objectives |
|-------|-------|----------|------------|
| Phase 2b | Phase 2b | 2025-2026 | Doseoptimization |
| Phase 3 | Phase 3 | 2026-2028 | Pivotal efficacy |
| Confirmatory | Phase 3 | 2028-2029 | Validation |
Companion Diagnostic Development
Integration with Therapeutics:
- Anti-amyloid antibody combination
- Patient selection for trials
- Treatment response monitoring
- Treatment discontinuation decisions
Cross-Links
- [Retinal Biomarkers for Alzheimer's Disease](/biomarkers/retinal-biomarkers-alzheimers)
- [Amyloid PET Imaging](/technologies/amyloid-pet-imaging)
- [Retinal Imaging](/technologies/retinal-imaging-neurodegeneration)
- [Optical Coherence Tomography](/technologies/optical-coherence-tomography)
- [Amyloid-Beta](/proteins/amyloid-beta)
- [APOE Genotyping](/diagnostics/apoe-genotyping)
- [CSF Biomarkers](/biomarkers/csf-biomarkers-neurodegenerative-disease)
- [Blood Biomarkers](/biomarkers/plasma-biomarkers-alzheimers)
- [P-tau 217](/biomarkers/p-tau-217)
References
[NCT06514001 - AMDX-2011P as a Retinal Tracer in AD](https://clinicaltrials.gov/study/NCT06514001)
[Amydis Inc](https://www.amydis.com)
[Retinal amyloid imaging for Alzheimer's disease diagnosis](https://pubmed.ncbi.nlm.nih.gov/xxxxx/)
[Correlation between retinal and brain amyloid in AD](https://pubmed.ncbi.nlm.nih.gov/xxxxx/)Pathway Diagram
The following diagram shows the key molecular relationships involving AMDX-2011P Retinal Amyloid Tracer in Alzheimer's Disease discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)