A Research Study to Look at How a New Medicine Called NNC6019-0001 Works and How Safe it is for People Who Have Heart Disease Due to Transthyretin (TTR) Amyloidosis
Study Details
Study Description
Brief Summary
This study is testing a potential new medicine, NNC6019-0001, for people who have a heart disease due to TTR amyloidosis.The study will look at if this medicine can reduce the symptoms of a heart disease due to TTR amyloidosis, such as heart failure. Participants will either get NNC6019-0001 (apotential new medicine) or placebo (a medicine which has no effect on the body). Which treatment participants get is decided by chance. The chance of getting NNC6019-0001 is two times higher than getting placebo. NNC6019-0001 is not yet approved in any country or region in the world. It is a new medicine that doctors cannot prescribe yet. Participants will get an infusion of the study medicine 13 times, once every 4 weeks. The study will last for about 64 weeks after the first dose of medicine. Participants cannot participate in this study if they have a heart disease other than a heart disease due to TTR amyloidosis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NNC6019-0001, 30 mg/kg Participants will receive intravenous (i.v.) infusion of 30 milligrams per kilograms (mg/kg) NNC6019-0001 every 4 weeks (Q4W) added to standard of care until week 52. |
Drug: NNC6019-0001
Participants will receive i.v infusion of either 30 mg/kg or 100 mg/kg NNC6019-0001.
|
| Experimental: NNC6019-0001, 100 mg/kg Participants will receive i.v. infusion of 100 mg/kg NNC6019-0001 Q4W added to standard of care until week 52. |
Drug: NNC6019-0001
Participants will receive i.v infusion of either 30 mg/kg or 100 mg/kg NNC6019-0001.
|
| Placebo Comparator: Placebo Participants will receive i.v. infusion of placebo (NNC6019-0001) Q4W added to standard of care until week 52. |
Drug: Placebo (NNC6019-0001)
Participants will receive i.v. infusion of placebo (NNC6019-0001).
|
Outcome Measures
Primary Outcome Measures
- Change in 6-minute walk test (6-MWT) [From baseline (week 0) to visit 15 (week 52)]
Measured in Meters
- Change in N-terminal-pro brain natriuretic peptide (NT-proBNP) [From baseline (week 0) to visit 15 (week 52)]
Measured in Percentage
Secondary Outcome Measures
- Change in myocardial extracellular volume (ECV) [From baseline (week 0) to visit 15 (week 52)]
Measured in Percentage (%)-points
- Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) [From baseline (week 0) to visit 15 (week 52)]
The KCCQ is a disease-specific health status instrument composed of 23 items that quantify the domains of physical limitation, symptoms, self-efficacy, social limitation, and health-related quality of life limitation from heart failure. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. CSS scores range from 0 to 100 and lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life.
- Change in neuropathy impairment score (NIS) [From baseline (week 0) to visit 15 (week 52)]
NIS is a clinical assessment that tests muscle strength, reflex activity, and sensation of toes and fingers, and can be used to assess neurologic function in hereditary transthyretin amyloid (hATTR). The total NIS score is graded on a scale of 0-244, with a higher score indicating greater impairment.
- Change in troponin I [From baseline (week 0) to visit 15 (week 52)]
Measured in nanogram per milliliter (ng/mL)
- Change in global longitudinal strain (GLS) on echocardiography [From baseline (week 0) to visit 15 (week 52)]
Measured in Percentage (%)-points
- Number of treatment emergent adverse events [From baseline (week 0) to visit 16 (week 64)]
Measured as Events
- Time to occurrence of all-cause mortality [From baseline (week 0) to visit 16 (week 64)]
Measured in Weeks
- Number of cardiovascular (CV) events comprising hospitalisation due to CV events or urgent heart failure visits [From baseline (week 0) to visit 16 (week 64)]
Measured as Events
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female.
-
Age greater than or equal to (>=) 18 to less than (<) 85 years at the time of signing informed consent.
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Have an established diagnosis of Transthyretin amyloid cardiomyopathy (ATTR CM) with either wild-type transhyretin (TTR) or hereditary transthyretin (TTR) genotype as per local standards.
-
Expected to be on stable doses of cardiovascular medical therapy 6 weeks prior to the randomisation visit.
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Known end-diastolic interventricular septal wall thickness greater than or equal to (>=) 12 millimeters (mm).
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Presently classified as New York Heart Association (NYHA) Class II-III.
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N-terminal-pro brain natriuretic peptide (NT-proBNP) concentration greater than or equal to (>=) 650 picograms per milliliter (pg/mL) in sinus cardiac rhythm and greater than (>) 1000 pg/mL in atrial fibrillation at screening.
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Completed greater than or equal to (>=) 150 meters to less than or equal to (<=) 450 meters on the 6-minute walk test (MWT) at screening.
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Estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 25 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) at screening.
Exclusion Criteria:
-
Cardiomyopathy not primarily caused by transthyretin amyloid cardiomyopathy transthyretin amyloid cardiomyopathy (ATTR CM), for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease.
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A prior solid organ transplant.
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Planned solid organ transplant during the study.
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Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, insitu carcinomas of the cervix, or in-situ/high grade prostatic intraepithelial neoplasia (PIN) or low-grade prostate cancer) within 5 years before screening.
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Current treatment with calcium channel blockers with conduction system effects (example [e.g.], verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed. The use of digoxin will only be allowed if required for management of atrial fibrillation with rapid ventricular response.
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Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac valve repair, or major surgery within 3 months of screening.
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Body weight >120 kilogram (kg) (264.6 pounds [lb]) at screening.
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History of contrast allergy or adverse reactions to gadolinium-containing agents.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Baltimore | Maryland | United States | 21201 |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
- Study Director: Clinical Transparency 2834, Novo Nordisk A/S
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NN6019-4940
- U1111-1271-3861
- 2021-006226-49