Transthyretin Amyloid Cardiomyopathy
Conditions
Brief summary
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.
Interventions
DRUGCoramitug
Coramitug will be administered intravenously
Sponsors
Novo Nordisk A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Standard Uptake Value Ratio (SUVRmean) in myocardium | Day 1-day 8 | Measured as ratio. |
| Net uptake rate constant (Ki) in myocardium | 0 to 168 hours | Measured as milliliter per minute per centimeter cube (mL/min/cm\^3). |
| Change in SUVRmean in myocardium | 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 | Measured as percentage (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | 0 to 168 hours | microcurie (μCi) |
| Time at which maximum plasma concentration is observed (Tmax) | 0 to 168 hours | Measured in hours. |
| Area under the curve (AUC) | 0 to 168 hours | Measured in microcurie \*hours (μCi\*h). |
| Terminal half-life (T1/2) | 0 to 168 hours | Measured in hours. |
| Cmax | 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2 | Measured in nanograms per milliliter (ng/mL). |
| Tmax | 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2 | Measured in hours. |
| AUC | 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2 | Measured in nanograms\*hours per milliliter (ng\*h/mL). |
| T1/2 | 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2 | Measured in hours. |
| Number of Treatment Emergent Adverse Events (TEAE) | From day 1 to day 8 in cohort 1 or day -1 to day 28 for cohort 2 | Measured as count of events. |
| Number of Treatment Emergent Adverse Events | 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 | Measured as count of events. |
Countries
Netherlands
Contacts
CONTACTNovo Nordisk
STUDY_DIRECTORClinical Transparency dept. 2834
Novo Nordisk A/S
Outcome results
None listed