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 TTR amyloidosis

Phase 1

• Conditions: Transthyretin amyloid cardiomyopathy (ATTR CM); MedDRA version: 20.0Level: LLTClassification code 10002020Term: Amyloid cardiomyopathySystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2021-006226-49-CZ
• Lead Sponsor: ovo Nordisk A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-08-23
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

1. Male or female.
2. Age greater than or equal to 18 to below 85 years at the time of signing informed consent.
3. Have an established diagnosis of ATTR CM with either wild-type TTR or hereditary TTR genotype as per local standards.
4. Expected to be on stable doses of cardiovascular medical therapy 6 weeks prior to the randomisation visit.
5, Known end-diastolic interventricular septal wall thickness greater than or equal to12 mm.
6. Presently classified as New York Heart Association (NYHA) Class II-III.
7. NT-proBNP concentration greater than or equal to 650 pg/mL in sinus cardiac rhythm and greater than1000 pg/mL in atrial fibrillation at screening.
8. Completed greater than or equal to 150 meters to equal to or below 450 meters on the 6-MWT at screening.
9. Estimated glomerular filtration rate (eGFR) greater than or equal to 25 mL/min/1.73 m^2 at screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 19

Exclusion Criteria

1. Cardiomyopathy not primarily caused by ATTR CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease
2. A prior solid organ transplant.
3. Planned solid organ transplant during the study.
4. Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in-situ carcinomas of the cervix, or in-situ/high grade prostatic intraepithelial neoplasia (PIN) or low-grade prostate cancer) within 5 years before screening.
5. Current treatment with calcium channel blockers with conduction system effects (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.
6. Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac valve repair, or major surgery within 3 months of screening.
7. Body weight greater than 120 kg (264.6 lb) at screening.
9. History of contrast allergy or adverse reactions to gadolinium-containing agents.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the effect of two dose levels of NNC6019-0001 (10 mg/kg and 60 mg/kg) versus placebo on: <br>•change in 6-minute walk test and<br>•change in NT-proBNP <br>from baseline to week 52 in participants with hATTR or wtATTR cardiomyopathy.;Secondary Objective: 1) To compare the effect of two dose levels of NNC6019-0001 (10 mg/kg and 60 mg/kg) versus placebo on:<br>•biomarkers<br>•pharmacodynamic endpoints<br>from baseline to week 52 in participants with hATTR or wtATTR cardiomyopathy. <br>2) To compare the effect of two dose levels of NNC6019-0001 (10 mg/kg and 60 mg/kg) versus placebo on:<br>•safety and tolerability<br>from baseline to week 64 in participants with hATTR or wtATTR cardiomyopathy.;Primary end point(s): 1. Change in 6-minute walk test (6-MWT)<br>2. Change in NT-proBNP;Timepoint(s) of evaluation of this end point: 1.-2.From baseline (week 0) to visit 15 (week 52)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Change in myocardial extracellular volume (ECV)<br>2. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)<br>3. Change in neuropathy impairment score (NIS)<br>4. Change in troponin I<br>5. Change in global longitudinal strain (GLS) on echocardiography <br>6. Number of treatment emergent adverse events<br>7. Time to occurrence of all-cause mortality <br>8. Number of CV events comprising hospitalisation due to CV events or urgent heart failure visits;Timepoint(s) of evaluation of this end point: 1.-5. From baseline (week 0) to visit 15 (week 52)<br>6.-8.From baseline (week 0) to visit 16 (week 64)