Study of AMDX-2011P in Subjects With CAA

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 cerebral amyloid angiopathy (CAA).

Detailed Description
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This open, blinded endpoint assessment study will evaluate the activity, safety, tolerability, and pharmacokinetics (PK) of escalating intravenous (IV) doses of AMDX-2011P in CAA subjects. Assessments of retinal images will be conducted by central masked assessors. 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 up to 20 adult (=/>18 years of age) subjects diagnosed with hereditary CAA or probable or definite CAA according to the modified Boston neuroradiological criteria.

Official Title
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Open Label, Blinded Endpoint Assessment Study of AMDX-2011P as a Retinal Tracer in Subjects With Cerebral Amyloid Angiopathy (CAA)

Conditions
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Cerebral Amyloid Angiopathy

Intervention / Treatment
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* Drug: AMDX-2011P


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: .Diagnosis of hereditary CAA or probable and definite symptomatic or asymptomatic sporadic CAAdiagnosed through genetic testingoraccording to the modified Boston neuroradiological criteria(Table 9), who had undergone at least one brain magnetic resonance imaging (MRI)prior to entry into study. Abnormality consistent with CAA on historical MRI. No other causes of cerebral hemorrhage (brain tumors, arteriovenous malformations, aneurysms, cavernous angiomas). Male and female subjects 18 years and older at the time of signing the informed consent. Ability to undergo retinal imagingfor both eyes 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 caregiver can sign on their behalfin presence of an independent witness. Contraception use by study subjects of childbearing potential (male and female) and female partners of childrearing potential male subjectsshould be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For details,refer to Section10.3. Female subjects of childbearing potential and female partners of childbearing potential male subjects must refrain from oocyte donation for up to 30 days after study drug administration. Male subjects must refrain from sperm donation for90 days after study drug administration.1 Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1. Females not of childbearing potential must be surgically infertile or postmenopausal (defined as cessation of regular menstrual periods for at least 12 months) at Screening. Exclusion Criteria: Presence of any underlying physical or psychological medical condition that, in the opinion of the investigator, would make it unlikely that the subject will complete the study per protocol. Clinically significantlaboratory abnormalitiesassessed 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, in the opinion of the investigator, 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). These conditions may include, but are not limited to; age-related macular degeneration, central serous chorioretinopathy, diabetic retinopathy, macular dystrophies such as Stargardt disease, retinitis pigmentosa, choroideremia, white dot syndromes, and drug toxicities such as hydroxychloroquine toxicity. Use of any new prescription therapies or vaccines within 7days prior to study drug administration. Drugs with potential phototoxicity per Package Insert are prohibited within 48hoursor 5half-lives, whichever is longer, prior to first study drug until End-of-Study (EOS)visit, except for those required for treatment of underlying disease. Examples of such drugs include the following: Chloroquine (Aralen), hydroxychloroquine (Plaquenil), Thioridazine (Mellaril), Topiramate (Topamax), vemurafenib, voriconazole, doxycycline, hydrochlorothiazide, amiodarone, furosemide, allopurinol, phenothiazine, and chlorpromazine. 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 (4 total cohorts)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMDX-2011P 50 mg<br>AMDX2011P 50mg (2ml) single bolus injection intravenous for diagnostic review | Drug: AMDX-2011P<br>* AMDX-2011P single bolus injection intravenous for diagnostic review<br>|
| Experimental: AMDX-2011P 100 mg<br>AMDX2011P 100mg (4ml) single bolus injection intravenous for diagnostic review | Drug: AMDX-2011P<br>* AMDX-2011P single bolus injection intravenous for diagnostic review<br>|
| Experimental: AMDX-2011P 150 mg or 200 mg<br>AMDX2011P 200mg (6-8ml) single bolus injection intravenous for diagnostic review | Drug: AMDX-2011P<br>* AMDX-2011P single bolus injection intravenous for diagnostic review<br>|
| Experimental: AMDX-2011P TBD<br>AMDX2011P (dose TBD) single bolus injection intravenous for diagnostic review | Drug: AMDX-2011P<br>* AMDX-2011P 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 CAA | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of Amyloid Deposits in the Retina After AMDX-2011P Administration | The presence of hyperfluorescent spots in retinal images | 6 hours | 
| Concentration of AMDX-2011P | Peak plasma concentration (Cmax) | 6 hours | 
| Pharmacokinetic Concentration | Area under the plasma concentration versus time curve (AUC) | 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAA