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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

23 May 2023 → 13 May 2025

Decision date (initial)

2023-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2023-506824-96-00

EudraCT number

2021-006226-49

WHO UTN

U1111-1271-3861

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety

To compare the effect of two dose levels of NNC6019-0001 (xx and xx) versus placebo on, change in 6-minute walk test and change in NT-proBNP from baseline to week 52 in participants with hereditary ATTR (hATTR) or wild-type ATTR (wtATTR) cardiomyopathy.

Secondary objectives 2

1. To compare the effect of two dose levels of NNC6019-0001 (xx and xx) versus placebo on biomarkers and pharmacodynamic endpoints from baseline to week 52 in participants with hATTR or wtATTR cardiomyopathy
2. To compare the effect of two dose levels of NNC6019-0001 (xx and xx) versus placebo on safety and tolerability from baseline to week 64 in participants with hATTR or wtATTR cardiomyopathy.

Conditions and MedDRA coding

The present study will include a population of patients with established ATTR CM.

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female.
2. Age ≥ 18 to < 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 ≥ 12 mm.
6. Presently classified as New York Heart Association (NYHA) Class II-III.
7. NT-proBNP concentration ≥650 pg/mL in sinus cardiac rhythm and >1000 pg/mL in atrial fibrillation at screening.
8. Completed ≥150 meters to ≤450 meters on the 6MWT at screening.
9. Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 at screening.

Exclusion criteria 8

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 >120 kg (264.6 lb) at screening.
8. History of contrast allergy or adverse reactions to gadolinium-containing agents.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change in 6-minute walk test (6MWT) from baseline (week 0) to visit 15 (week 52)
2. Change in NT-proBNP from baseline (week 0) to visit 15 (week 52)

Secondary endpoints 8

1. Change in myocardial extracellular volume (ECV) from baseline (week 0) to visit 15 (week 52)
2. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) from baseline (week 0) to visit 15 (week 52)
3. Change in neuropathy impairment score (NIS) (only hATTR patients) from baseline (week 0) to visit 15 (week 52)
4. Change in troponin I from baseline (week 0) to visit 15 (week 52)
5. Change in global longitudinal strain (GLS) on echocardiography from baseline (week 0) to visit 15 (week 52)
6. Number of treatment emergent adverse events from baseline (week 0) to visit 16 (week 64)
7. Time to occurrence of all-cause mortality from baseline (week 0) to visit 16 (week 64)
8. Number of CV events comprising hospitalisation due to CV events or urgent heart failure visits (week 0) to visit 16 (week 64)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 8

Locations

7 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 75 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications