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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

Phase 2
Active, not recruiting
Conditions
Transthyretin Amyloid Cardiomyopathy (ATTR CM)
Interventions
Drug: Placebo (NNC6019-0001)
Registration Number
NCT05442047
Lead Sponsor
Novo Nordisk A/S
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
99
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NNC6019-0001, Dose 1NNC6019-0001Participants will receive dose 1 intravenous (i.v.) infusion of NNC6019-0001 every 4 weeks (Q4W) added to standard of care until week 52.
PlaceboPlacebo (NNC6019-0001)Participants will receive i.v. infusion of placebo (NNC6019-0001) Q4W added to standard of care until week 52.
NNC6019-0001, Dose 2NNC6019-0001Participants will receive dose 2 i.v. infusion of NNC6019-0001 Q4W added to standard of care until week 52.
Primary Outcome Measures
NameTimeMethod
Change in N-terminal-pro brain natriuretic peptide (NT-proBNP)From baseline (week 0) to visit 15 (week 52)

Measured in Percentage

Change in 6-minute walk test (6-MWT)From baseline (week 0) to visit 15 (week 52)

Measured in Meters

Secondary Outcome Measures
NameTimeMethod
Change in troponin IFrom baseline (week 0) to visit 15 (week 52)

Measured in nanogram per milliliter (ng/mL)

Number of treatment emergent adverse eventsFrom baseline (week 0) to visit 16 (week 64)

Measured as Events

Change in myocardial extracellular volume (ECV)From baseline (week 0) to visit 15 (week 52)

Measured in Percentage (%)-points

Number of cardiovascular (CV) events comprising hospitalisation due to CV events or urgent heart failure visitsFrom baseline (week 0) to visit 16 (week 64)

Measured as Events

Change in global longitudinal strain (GLS) on echocardiographyFrom baseline (week 0) to visit 15 (week 52)

Measured in Percentage (%)-points

Time to occurrence of all-cause mortalityFrom baseline (week 0) to visit 16 (week 64)

Measured in Weeks

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.

Trial Locations

Locations (32)

Universitair Medisch Centrum Utrecht

🇳🇱

Utrecht, Netherlands

Hospital Universitario Puerta de Hierro Majadahonda

🇪🇸

Madrid, Spain

Uniklinik Münster, Klinik für Kardiologie I

🇩🇪

Münster, Germany

LMU Klinikum München Klinik und Poliklinik 1

🇩🇪

München, Germany

Universitatsklinikum Wurzburg AöR

🇩🇪

Würzburg, Germany

Universitatsklinikum Würzburg - Zentrum für Herzinsuffizienz

🇩🇪

Würzburg, Germany

Fondazione CNR-Regione Toscana Gabriele Monasterio

🇮🇹

Pisa, Pi, Italy

Univ of MD Schl of Med

🇺🇸

Baltimore, Maryland, United States

Universitätsklinik Heidelberg Innere Medizin III Kardiologie, Angiologie, Pneumologie

🇩🇪

Heidelberg, Germany

Hospital da Senhora da Oliveira - Guimarães

🇵🇹

Guimarães, Portugal

Unidade Local de Saude do Alto Ave, E.P.E.

🇵🇹

Guimarães, Portugal

Kumamoto University Hospital, Cardiovascular Medicine

🇯🇵

Kumamoto-shi, Kumamoto, Japan

Mayo Clinic Arizona

🇺🇸

Phoenix, Arizona, United States

Cedars-Sinai Medical Center_Los Angeles

🇺🇸

Beverly Hills, California, United States

Stanford Hlth Cre-Boswell Clin

🇺🇸

Stanford, California, United States

Mayo Clinic Jacksonville

🇺🇸

Jacksonville, Florida, United States

Shinshu University Hospital, Department of Neurology

🇯🇵

Nagano, Japan

NW Univ-Bluhm Cardiovasc Inst

🇺🇸

Evanston, Illinois, United States

University of Maryland School of Medicine

🇺🇸

Baltimore, Maryland, United States

Mayo Clinic Rochester

🇺🇸

Rochester, Minnesota, United States

Oregon Hlth Sci Univ-Portland

🇺🇸

Portland, Oregon, United States

University of Calgary_Cardiology

🇨🇦

Calgary, Alberta, Canada

Ctr for Cardiovascular Innovation

🇨🇦

Vancouver, British Columbia, Canada

II. interni klinika VFN - Kardiologie a angiologie

🇨🇿

Praha 2, Czechia

Ap-Hp-Hopital Henri Mondor

🇫🇷

Créteil, France

Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-1

🇫🇷

Toulouse Cedex 9, France

Nagasaki University Hospital, Cardiovascular Medicine

🇯🇵

Nagasaki, Japan

Okayama University Hospital_Cardiovascular Medicine

🇯🇵

Okayama-shi, Okayama, Japan

UMC Groningen

🇳🇱

Groningen, Netherlands

Centro per lo Studio e la Cura delle Amiloidosi Sistemiche Fondazione IRCCS Policlinico San Matteo

🇮🇹

Pavia, PV, Italy

Hospital of the University of Occupational and Environmental Health, Cardiology, Nephrology

🇯🇵

Fukuoka, Japan

Hiroshima University hospital, Cardiovascular Medicine

🇯🇵

Hiroshima, Japan

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