A Research Study to Look at the Distribution and Effects of Coramitug on Amyloid Deposits in Heart Tissue Using PET/CT Imaging in People With ATTR Amyloidosis.

Официальное название

An Open-label Study to Evaluate the Biodistribution of 89Zr-coramitug and Investigate the Effects of Coramitug on Depleting TTR Amyloid Deposits in Myocardial Tissues Using PET/CT Imaging in Participants With ATTR-CM

Обзор

The study is conducted in participants with Transthyretin Amyloid Cardiomyopathy (ATTR-CM), a heart disease that occurs in people with the disease ATTR amyloidosis. The purpose of this study is to see how radioactively labelled coramitug is taken up by the heart after administration through an infusion (Cohort 1), and to understand the extent to which coramitug can be displaced by radioactively labelled coramitug (Cohort 2). In this study it will also be investigated how safe coramitug is and how well it is tolerated when it is used by participants with ATTR-CM. Coramitug is potentially a new medicine for participants with ATTR-CM. Coramitug is a monoclonal antibody that potentially binds to the accumulations of the transthyretin protein and promotes its removal from the heart. It may also prevent the formation of clumps and may help with clearing existing clumps of the abnormal protein. The study will take a maximum of 85 days (for Cohort 1) or 106 days (for Cohort 2) when participating in Period A from the screening until the follow-up visit.

Вмешательства

• Препарат Coramitug
  Coramitug will be administered intravenously

Первичные конечные точки

• Mean Standard Uptake Value Ratio (SUVRmean) in myocardium [Срок оценки: Day 1-day 8]
• Net uptake rate constant (Ki) in myocardium [Срок оценки: 0 to 168 hours]
• Change in SUVRmean in myocardium [Срок оценки: From baseline to week 52 (day 364), or week 60 (day 420) if there is no uptake expected/observed when both unradiolabelled and radiolabelled compounds are administered together]

Вторичные конечные точки (10)

• Maximum Plasma Concentration (Cmax) [Срок оценки: 0 to 168 hours]
• Time at which maximum plasma concentration is observed (Tmax) [Срок оценки: 0 to 168 hours]
• Area under the curve (AUC) [Срок оценки: 0 to 168 hours]
• Terminal half-life (T1/2) [Срок оценки: 0 to 168 hours]
• Cmax [Срок оценки: 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2]
• Tmax [Срок оценки: 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2]
• AUC [Срок оценки: 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2]
• T1/2 [Срок оценки: 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2]
• Number of Treatment Emergent Adverse Events (TEAE) [Срок оценки: From day 1 to day 8 in cohort 1 or day -1 to day 28 for cohort 2]
• Number of Treatment Emergent Adverse Events [Срок оценки: From baseline to week 52 (day 364), or week 64 (day 448) if there is no uptake expected/observed when both unradiolabelled and radiolabelled compounds are administered together]

Критерии участия

Критерии включения

• Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
• Male or female.
• Age greater than or equal to (≥) 60 years or above at the time of signing the informed consent.
• For participants with Transthyretin Amyloid Cardiomyopathy (ATTR-CM):
• Have an established diagnosis of ATTR-CM, with either wild-type Transthyretin (TTR) or variant TTR genotype (ATTRwt) or (ATTRv), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, \& heart failure (HF):

a) Cardiac amyloid infiltration demonstrated by: i. Cardiac biopsy positive for TTR amyloid, OR ii. Grade 2 or Grade 3 cardiac uptake at pyrophosphate/3,3-diphosphono-1,2-propanodicarboxylic acid/hydroxymethylene diphosphonate (PYP/DPD/HMDP) scintigraphy with Single-Photon Emission Computed Tomography (SPECT/CT) combined with an extracardiac biopsy positive for TTR amyloid, OR iii. Grade 2 or Grade 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combined with normal serum free light chain ratio \& negative serum \& urine immunofixation (Serum Immunofixation \[SPIE\] and Urine Immunofixation \[UPIE\]) Note: Bone tracer scintigraphy using 99m technetium (Tc)-labelled pyrophosphate (99mTc-PYP)/99mTc-labelled 3,3-diphosphono-1,2- propanodicarboxylic acid (99mTc-DPD)/99mTc-labeled hydroxymethylene diphosphonate (99m-Tc-HMDP) b. Increased LV wall thickness, as assessed by echocardiography showing LV posterior and septal wall thickness greater than or equal to (≥)13 millimeter (mm) for women and ≥ 14 mm for men (Note: Pre-existing echocardiogram up to 2 years old can be used).

c. Chronic HF with: i. At least 1 documented hospitalisation for HF occurring greater than (>) 3 months but less than (<) 2 years, OR ii. History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary con-gestion on x-ray or auscultation, or peripheral oedema) requiring ongoing treatment with a loop diuretic.

Критерии исключения

• Known or suspected hypersensitivity to study intervention(s) or related products.
• Previous participation in this study. Participation is defined as signed informed consent.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential.
• Current participation (i.e., signed informed consent) in any other interventional clinical study.
• Participation in research studies involving exposure to radiation within a year preceding the screening period in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• ICON - location Groningen — Groningen

Идентификаторы

NCT: NCT07448623 · NN6019-7853 · U1111-1316-9198 · 2024-519372-22

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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