AMDX-2011P Retinal Tracer in Subjects With Neurodegenerative Diseases Associated With Amyloidogenic Proteinopathy

Study Overview
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Brief Summary
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The purpose of this research study is to assess safety and tolerability of a single intravenous (given through a vein) dose of the investigational retinal tracer AMDX-2011P in patients with neurodegenerative diseases (Parkinson's disease and ALS).

Detailed Description
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This study will also evaluate the ability of AMDX-2011P to identify α-syn in the retina of patients with Parkinson's disease and to identify the protein TDP-43 in the retina of patients with ALS. This study will help to evaluate the ability to detect these protein deposits for the purpose of diagnosing PD and ALS. To determine the safest dose, participants will receive different amounts of the investigational retinal tracer. The first group of participants taking part in the study will receive a low dose of AMDX-2011P. If no major side effects occur, the dose will be increased for the next group of participants. Participants will receive a 1 time intravenous injection. This study plans to enroll approximately 24-36 subjects with active disease (PD or ALS). Participants will be age 18 and older.

Official Title
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Prospective Randomized Open, Blinded Endpoint (PROBE) Study of AMDX-2011P as a Retinal Tracer in Subjects With Neurodegenerative Diseases Associated With Amyloidogenic Proteinopathy

Conditions
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Parkinson Disease, Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: AMDX2011P


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Subjects with Parkinson's Disease Clinically established Parkinson's disease based on Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's disease (Table 8) and a modified Hoehn & Yahr scale of 1-3 (Table 9). No suspected atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis, or degenerative diseases. For Subjects with ALS Confirmed diagnosis of ALS with both upper and lower motor neuron involvement. For All Subjects Ability to undergo retinal imaging. Subject or legally authorized representative must provide signed informed consent (or signed assent form) prior to study entry and have the ability and willingness to attend and comply with the necessary study procedures and visits at the study site. For subjects unable to physically sign the informed consent, a guardian or trusted care giver can sign on their behalf in presence of an independent witness. Contraception use by study subjects of childbearing potential (male and female) and female partners of childrearing potential male subjects should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Exclusion Criteria: Presence of any underlying physical or psychological medical condition that would make it unlikely that the subject will complete the study per protocol. Clinically significant laboratory abnormalities assessed by the investigator. Active malignancy and/or history of malignancy in the past 5 years, with the exception of completely excised non-melanoma skin cancer or low-grade cervical intraepithelial neoplasia. Prolonged QTcF (>450 ms for males and >470 ms for females), cardiac arrhythmia, or any clinically significant abnormality in the resting ECG, as judged by the investigator. Presence of any ocular condition that would significantly hinder the ability to detect and quantify hyper-fluorescent puncta (e.g., eyes with significant hyper-autofluorescence that would mask the ability to detect, quantify, and discern post-injection hyper-fluorescent signal from pre-injection hyper-autofluorescence signal). Use of any new prescription therapies or vaccines within 7 days prior to the study drug administration. Drugs with potential phototoxicity per Package Insert are prohibited within 48 hours or 5 half-lives, whichever is longer, prior to first study drug until End-of-study (EOS) visit, except for those required for treatment of underlying disease. Administration of investigational product in another study within 30 days prior to the first study drug administration, or five half-lives, whichever is longer. Females who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalating via Cohorts total 1-4 cohorts
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMDX2011P 25mg<br>25mg (1ml) single bolus injection intravenous for diagnostic review | Drug: AMDX2011P<br>* AMDX2011P single bolus injection intravenous for diagnostic review<br>|
| Experimental: AMDX2011P 50mg<br>AMDX2011P 50mg (2ml) single bolus injection intravenous for diagnostic review | Drug: AMDX2011P<br>* AMDX2011P single bolus injection intravenous for diagnostic review<br>|
| Experimental: AMDX2011P 100mg<br>AMDX2011P 100mg (4ml) single bolus injection intravenous for diagnostic review | Drug: AMDX2011P<br>* AMDX2011P single bolus injection intravenous for diagnostic review<br>|
| Experimental: AMDX2011P 200mg<br>AMDX2011P 200mg (6-8ml) single bolus injection intravenous for diagnostic review | Drug: AMDX2011P<br>* AMDX2011P single bolus injection intravenous for diagnostic review<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AMDX-2011P adverse events profile | Rate and nature of adverse events after a single intravenous (IV) dose of AMDX-2011P in subjects with neurodegenerative diseases (Parkinson's disease and ALS). | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of a-syn and TDP-43 deposits in retina | The presence of hyperfluorescent spots in retinal images | 8 hours | 
| Concentration of AMDX-2011P | Peak Plasma Concentration (Cmax) | 8 hours | 
| Pharmacokinetic Analysis of AMDX-2011P | Area under the plasma concentration versus time curve (AUC) | 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinsons, ALS