The CARDIO-TTRansform Scintigraphy Sub-study

Study Overview
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Brief Summary
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The purpose of this study is to examine the changes in amyloid myocardial burden in a subset of the population participating in the ION682884-CS2 (NCT04136171) study, up to 150 participants, after treatment with eplontersen or placebo based on scintigraphy scans performed at Week 140 using the Perugini grade score method.

Detailed Description
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Participants who were randomized in Study ION-682884-CS2 (NCT04136171) and have had a baseline scintigraphy scan will be offered the opportunity to participate in this sub-study which involves optional scintigraphy scans.

Official Title
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CARDIO-TTRansform ION-682884-CS2-Scintigraphy Sub-study

Conditions
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Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)

Intervention / Treatment
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* Diagnostic Test: Scintigraphy scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have been properly randomized into the ION-682884-CS2 study (NCT04136171) and should have had a baseline scintigraphy scan (99mTc-DPD, 99mTc- PYP, and 99mTc-HMDP) within 12 months prior to screening for ION-682884-CS2 with planar and SPECT or SPECT/CT images that can be read by the central reader. Exclusion criteria: Must not meet any of the exclusion criteria of the study protocol ION-682884-CS2 (NCT04136171). Must not have weight or body girth that exceeds the limits of the equipment specifications. Should not have any previously reported hypersensitivity reaction to Technetium-99m.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ION-682884-CS2 Scintigraphy Subset<br>Participants randomized in ION-682884-CS2 (NCT04136171) study to receive either eplontersen or placebo with baseline scintigraphy scan with planar and single-photon emission computerized tomography (SPECT) or SPECT with computed tomography (SPECT/CT) images will undergo an optional scintigraphy scan at Weeks 25 or 37, Week 97, and an additional scan at Week 140. | Diagnostic Test: Scintigraphy scan<br>* Scans will be performed as specified in the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline in Perugini Grading Score From Scintigraphy Scan Images at Week 140 | The Perugini grading scale visually compares tracer uptake in the myocardium and ribs following injection of the bone tracers (99mTc-DPD, 99mTc-Pyrophosphate [PYP], or 99mTc-HMDP). The scale includes 4 grade classifications: Grade 0- no cardiac uptake and normal rib uptake, Grade 1- cardiac uptake which is less than rib uptake, Grade 2- cardiac uptake with intensity similar rib uptake, and Grade 3- cardiac uptake greater than rib uptake with mild or absent rib uptake. Visual scores of 2 or greater are classified as ATTR-positive and less than 2 are interpreted as ATTR-negative. | Baseline up to Week 140 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TTR, Amyloidosis, Cardiomyopathy