Coramitug PET/CT imaging to track and affect heart amyloid in ATTR-CM

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

This study tests whether a radioactive version of the antibody coramitug can be detected in and displaced from heart amyloid in people aged 60 and older with transthyretin amyloid cardiomyopathy, and whether the drug is safe and well tolerated.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: Novo Nordisk A/S (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 1 site (Groningen)
• Trial ID: NCT07448623 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional study enrolls adults with confirmed transthyretin amyloid cardiomyopathy and uses PET/CT imaging to measure how radiolabeled coramitug is taken up by the heart. Cohort 1 receives an infusion of radiolabeled coramitug to quantify cardiac uptake, while Cohort 2 examines displacement dynamics using radiolabeled coramitug. Safety and tolerability of coramitug are monitored through clinical assessments and follow-up visits over a period up to 85 or 106 days depending on cohort. The study is sponsored by Novo Nordisk A/S and conducted at a site in Groningen, Netherlands.

Who should consider this trial

Good fit: Adults aged 60 or older with established ATTR-CM (wild-type or variant) with cardiac amyloid confirmed by biopsy or by grade 2–3 PYP/DPD/HMDP uptake and increased left ventricular wall thickness are ideal candidates.

Not a fit: People under 60, those without confirmed ATTR-CM or with other causes of heart disease, or those with contraindications to PET/CT or monoclonal antibody therapy are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, coramitug could help clear transthyretin amyloid from the heart and potentially slow or improve heart failure related to ATTR-CM.

How similar studies have performed: Antibody-based approaches to clear cardiac amyloid are relatively new, with some encouraging early-phase and preclinical signals but no definitive large-scale proof of clinical benefit yet.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Where this trial is running

Groningen

• ICON - location Groningen — Groningen, Netherlands (Recruiting)

Study contacts

• Study coordinator: Novo Nordisk

Conditions Transthyretin Amyloid Cardiomyopathy