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 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.
| 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 |
- 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
- 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
- Confirmed diagnosis of Alzheimer's disease
- Positive amyloid beta PET scan indicating presence of amyloid pathology
- Willingness to undergo APOE genotyping
- Ability to fixate and complete retinal imaging procedures
- Glaucoma or suspected glaucoma
- Age-related macular degeneration (AMD)
- Clinically significant laboratory abnormalities
- Prolonged QTcF interval
- Cardiac arrhythmia or significant ECG abnormalities
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
AMDX-2011P is designed as a retinal amyloid tracer that:
- Binds to retinal amyloid deposits — The compound selectively binds to 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 retina
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 time
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 response
Amyloid-beta (Aβ) deposition is a hallmark pathological feature of Alzheimer's disease:
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
The amyloid-beta peptide is central to Alzheimer's disease pathology:
APP Processing:
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
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
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
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
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
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
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
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
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
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 Qualification:
- Analytical validation of detection method
- Clinical validation in target population
- Correlation with clinical endpoints
- Establishment of reference ranges
¶ 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
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
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 trials
Implementation Considerations:
- Required imaging expertise
- Equipment availability
- Training for interpretation
- Standardized protocols
- Quality assurance
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
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
Other Neurodegenerative Diseases:
Screening Applications:
- At-risk population screening
- Population-based testing
- Primary care integration
- Teleophthalmology potential
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
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
| 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 |
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
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 biomarkers
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
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
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
| 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 |
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
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
AMDX-2011P Formulation:
- Concentration: 100 mg single bolus
- Route: Intravenous injection
- Volume: 10 mL
- Vehicle: Sterile saline
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
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?
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 |
Integration with Therapeutics:
- Anti-amyloid antibody combination
- Patient selection for trials
- Treatment response monitoring
- Treatment discontinuation decisions