A Study to Evaluate Organ Level Uptake Repeatability of 124I AT-01 in Subjects With Systemic Amyloidosis

Study Overview
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Brief Summary
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This study is designed to assess the repeatability of organ-specific quantitation of radiotracer uptake following Positron Emission Tomography/Computed Tomography (PET/CT) imaging of AT- 01 in subjects with amyloid light chain (AL) or amyloid transthyretin (ATTR) systemic amyloidosis.

Detailed Description
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This is a multicenter, open label, single arm study in subjects with amyloid light chain (AL) or amyloid transthyretin (ATTR) systemic amyloidosis with visceral amyloid deposits. This study consists of a screening period of up to 30 days; two one-day treatment periods (Day 1 and Week 6); a safety follow-up 24-48 hours after the second administration of 124I AT-01, and a safety follow-up visit 28 days after the second administration of 124I-AT-01.

Official Title
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A Multicenter, Open-label, Single-arm, Phase 2 Study to Evaluate Safety and Organ Uptake Quantitation Repeatability of 124I AT-01 Using Positron Emission Tomography/X-ray Computed Tomography (PET/CT) in Subjects With Systemic Amyloidosis

Conditions
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Amyloidosis

Intervention / Treatment
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* Drug: I124-AT01 only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understands the study procedures and is capable of giving signed informed consent, as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Male or female ≥18 years of age. For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 90 days after the last dose of 124I-AT-01. A woman is considered of childbearing potential if she is postmenarchal, has not reached a postmenopausal state, and has not undergone surgical sterilization. Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Contraception methods that do not result in a failure rate of <1% per year such as cap, diaphragm, or sponge with spermicide, or male or female condom with or without spermicide, are not acceptable. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm, as defined below: a) With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 120 days (a spermatogenesis cycle) after the last dose of study intervention. Men must refrain from donating sperm during this same time period. Able to undergo two PET/CT scans as part of the study, including ability to lie supine for up to 1 hour. Has a history of AL or ATTR systemic amyloidosis with at least one organ with clinically demonstrable amyloid involvement defined by: AL systemic amyloidosis: Positive tissue biopsy for AL amyloid, and achieved a hematologic very good partial response or complete response based on their most recent assessment, and at least one of the following: 1) Organ biopsy positive for amyloid, or 2) Natriuretic peptide (NT-proBNP) >650 pg/mL, or 3) left ventricle septal wall thickness >12 mm by echocardiogram or cardiac magnetic resonance (CMR), or 4) 24-hour urine protein >500 mg, or 5) Urine albumin-to-creatinine ratio >300 mg/g ATTR (wild type or variant) systemic amyloidosis: Positive cardiac biopsy for ATTR amyloid, or at least two of the following: 1) Positive extracardiac tissue biopsy for ATTR amyloid or positive transthyretin gene mutation associated with amyloid, or 2) left ventricle septal wall thickness >12 mm by echocardiogram or CMR, or 3) pyrophosphate (PYP) scintigraphy with myocardial uptake ≥grade 2. Exclusion Criteria Is pregnant or breast-feeding. Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of psychosis. Has received in the last 6 months or are currently receiving treatment with anti-amyloid monoclonal antibody therapy or are expected to begin treatment prior to completing this study. Has received heparin or heparin analogs within 7 days of Day 1. Has a significant co-morbidity (e.g., Easter Cooperative Oncology Group (ECOG) score of 3 or greater), New York Heart Association (NYHA) Class IV heart failure, uncontrolled infection, or other ongoing serious illness. Has active thyroid disease. Has a known allergy to potassium iodine treatment. Is receiving hemodialysis or peritoneal dialysis. Has severe claustrophobia that would prevent completion of the PET/CT imaging protocol. Has received an investigational agent within five half-lives of the agent or 30 days, whichever is longer, prior to Screening. Has any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.

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
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm, no placebo, no comparator
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single arm<br>I-124 AT-01 | Drug: I124-AT01 only<br>* Intravenous injection of I124-AT01 on Day 1 and again at Week 6 followed by a full body Positron Emission Tomography/Computed Tomography (PET/CT) scan.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Repeatability of organ specific quantitation of radiotracer uptake at baseline and 6 weeks. | To evaluate the repeatability of organ-specific quantitation of radiotracer uptake following PET/CT imaging of 124I-AT-01 in subjects with AL or ATTR systemic amyloidosis at baseline and the repeated scan at 6 weeks. | Repeatability coefficient (Bland-Altman plots) associated with the quantification of radioactivity associated with organ level 124I-AT-01 uptake measurements at 6 weeks.. | 
| Repeatability of organ specific quantitation of radiotracer uptake at baseline and 6 weeks. | To evaluate the repeatability of organ-specific quantitation of radiotracer uptake following PET/CT imaging of 124I-AT-01 in subjects with AL or ATTR systemic amyloidosis at baseline and the repeated scan at 6 weeks. | intraclass correlation coefficient (ICC) associated with the quantification of radioactivity associated with organ level 124I-AT-01 uptake measurements at 6 weeks.. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events [safety and tolerability] | To characterize the safety and tolerability of repeat doses of 124I-AT-01 administered by IV infusion at 6 weeks (Visit 2) and the safety follow-up visits at 24-48 hours after the second infusion and 28 days after the second infusion. | Incidence of treatment-emergent adverse events (AEs) from Day 1 to End of Study (EOS), up to 14 weeks. | 
| Number of participants with abnormal hematology and chemistry laboratory test results. | Change from Baseline in hematology and chemistry laboratory values at Visits 2 and Safety Follow-up 1 (24-48 hours after the second infusion). | At visit 2 (week 6) and Safety Follow-Up 1 at 24-48 hours after the second infusion (up to 48 hours after the week 6 visit).. | 
| Number of participants with abnormal vital signs. | Any abnormal change from Baseline in blood pressure and pulse measurements at visit 2 (week 6) and at the safety follow-up visit 24-48 hours after the week 6 visit and again at 28 days after the week 6 visit. | Change from Baseline in vital signs at visit 2 (week 6) and safety follow-ups at 24-48 hours after the second infusion (week 6) and 28 days after the second infusion at the week 6 visit.. | 
| Change from Baseline in anti-drug antibody (ADA). | Change from Baseline in anti-drug antibody (ADA). | Visit 2 (week 6) and safety follow-up 2 at 28 days following the second infusion at week 6. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyloid light chain (AL), Amyloid Transthyretin Systemic Amyloidosis (ATTR)