Clinical trial NCT05442047: 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
Official title: Efficacy and Safety of NNC6019-0001 at Two Dose Levels in Participants With Transthyretin Amyloid Cardiomyopathy (ATTR CM)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Transthyretin Amyloid Cardiomyopathy (ATTR CM)
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2022-07-01
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.
* 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.
* Known end-diastolic interventricular septal wall thickness greater than or equal to (\>=) 12 millimeters (mm).
* Presently classified as New York Heart Association (NYHA) Class II-III.
* 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.
* 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.
* 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.
* A prior solid organ transplant.
* Planned solid organ transplant during the study.
* 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.
* 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.
* Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac valve repair, or major surgery within 3 months of screening.
* Body weight \>120 kilogram (kg) (264.6 pounds \[lb\]) at screening.
* History of contrast allergy or adverse reactions to gadolinium-containing agents.

Primary outcomes:
measure: Change in 6-minute walk test (6-MWT)
timeFrame: From baseline (week 0) to visit 15 (week 52)
measure: Change in N-terminal-pro brain natriuretic peptide (NT-proBNP)
timeFrame: From baseline (week 0) to visit 15 (week 52)
Secondary outcomes:
measure: Change in myocardial extracellular volume (ECV)
timeFrame: From baseline (week 0) to visit 15 (week 52)
measure: Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)
timeFrame: From baseline (week 0) to visit 15 (week 52)
measure: Change in neuropathy impairment score (NIS)
timeFrame: From baseline (week 0) to visit 15 (week 52)
measure: Change in troponin I
timeFrame: From baseline (week 0) to visit 15 (week 52)
measure: Change in global longitudinal strain (GLS) on echocardiography
timeFrame: From baseline (week 0) to visit 15 (week 52)
measure: Number of treatment emergent adverse events
timeFrame: From baseline (week 0) to visit 16 (week 64)
measure: Time to occurrence of all-cause mortality
timeFrame: From baseline (week 0) to visit 16 (week 64)
measure: Number of cardiovascular (CV) events comprising hospitalisation due to CV events or urgent heart failure visits
timeFrame: From baseline (week 0) to visit 16 (week 64)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Center_Los Angeles
state: California
city: Stanford
country: United States
facility: Stanford Hlth Cre-Boswell Clin
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Evanston
country: United States
facility: NW Univ-Bluhm Cardiovasc Inst
state: Illinois
city: Baltimore
country: United States
facility: Univ of MD Schl of Med
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Portland
country: United States
facility: Oregon Hlth Sci Univ-Portland
state: Oregon
city: Calgary
country: Canada
facility: University of Calgary_Cardiology
state: Alberta
city: Vancouver
country: Canada
facility: Ctr for Cardiovascular Innovation
state: British Columbia
city: Praha 2
country: Czechia
facility: II. interni klinika VFN - Kardiologie a angiologie
city: Créteil
country: France
facility: Ap-Hp-Hopital Henri Mondor
city: Toulouse Cedex 9 TSA 50032
country: France
facility: Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-1
city: Toulouse Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-1
city: Heidelberg
country: Germany
facility: Universitätsklinik Heidelberg Innere Medizin III Kardiologie, Angiologie, Pneumologie
city: München
country: Germany
facility: LMU Klinikum München Klinik und Poliklinik 1
city: Münster
country: Germany
facility: Uniklinik Münster, Klinik für Kardiologie I
city: Würzburg
country: Germany
facility: Universitatsklinikum Wurzburg AöR
city: Würzburg
country: Germany
facility: Universitatsklinikum Würzburg - Zentrum für Herzinsuffizienz
city: Pisa
country: Italy
facility: Fondazione CNR-Regione Toscana Gabriele Monasterio
state: Pi
city: Pavia
country: Italy
facility: Centro per lo Studio e la Cura delle Amiloidosi Sistemiche Fondazione IRCCS Policlinico San Matteo
state: PV
city: Fukuoka
country: Japan
facility: Hospital of the University of Occupational and Environmental Health, Cardiology, Nephrology
city: Hiroshima
country: Japan
facility: Hiroshima University hospital, Cardiovascular Medicine
city: Kumamoto-shi, Kumamoto
country: Japan
facility: Kumamoto University Hospital, Cardiovascular Medicine
city: Nagano
country: Japan
facility: Shinshu University Hospital, Department of Neurology
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital, Cardiovascular Medicine
city: Okayama-shi, Okayama
country: Japan
facility: Okayama University Hospital_Cardiovascular Medicine
city: Groningen
country: Netherlands
facility: UMC Groningen
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Guimarães
country: Portugal
facility: Hospital da Senhora da Oliveira - Guimarães
city: Guimarães
country: Portugal
facility: Unidade Local de Saude do Alto Ave, E.P.E.
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency 2834
role: STUDY_DIRECTOR
References: