CLEOPATTRA: A research study to look at the effects of treatment with a medicine called coramitug (NNC6019-0001) in people with heart failure due to ATTR 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

19 Dec 2025 → ongoing

Decision date (initial)

2025-12-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2024-518899-31-00

WHO UTN

U1111-1315-5366

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis, Pharmacodynamic, Therapy, Dose response, Pharmacokinetic, Safety

To demonstrate superiority of NNC6019-0001 versus placebo, both added to SoCa, in reducing CV death and morbidity in participants with ATTRwt‑CM or ATTRv‑CM

Secondary objectives 1

1. To demonstrate superiority of NNC6019-0001 versus placebo, both added to SoCa, in participants with ATTRv-CM or ATTRwt-CM on: • HF symptoms, physical functioning and QoL • CV morbidity • CV death b and all-cause death b • Kidney function

Conditions and MedDRA coding

Variant or wild-type transthyretin (TTR) amyloid cardiomyopathy

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Male or female.
2. 2. Age 18 years or above at the time of signing the informed consent.
3. 3. Have an established diagnosis of ATTR-CM, (ATTRwt or ATTRv), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF. Note: Target ATTRv recruitment is approximately 15% of the study population. a. Cardiac amyloid infiltration demonstrated by: i. Cardiac biopsy positive for TTR amyloid, OR, ii. Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with single-photon emission computed tomography (SPECT/CT) combined with an extracardiac biopsy positive for TTR amyloid, OR, iii. Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE & UPIE). Notes: o Non-invasive diagnostic pathway will be confirmed by a centralised expert review. o Bone tracer scintigraphy will be conducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP)/99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc DPD)/99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP). b. Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness ≥12 mm. c. Chronic HF (New York Heart Classification [NYHA] I-IV) requiring ongoing treatment with a loop diuretic with: i. At least 1 documented hospitalisation for HF, OR ii. History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on x-ray or auscultation, or peripheral oedema).
4. 4. Expected to be on stable CV medical therapy (defined as no greater than 50% dose adjustment and no categorical changes of medications), with the exception of diuretics, 4 weeks prior to the randomisation visit.
5. 5. NT-proBNP concentration ≥"CCI" pg/mL at screening. Note: Participants with NT-proBNP levels between "CCI" and "CCI" pg/mL may be enrolled until a cap of 35% of the total study population is reached.
6. 6. Completed >50 meters on the 6MWT at screening.

Exclusion criteria 13

1. 1. Known or suspected hypersensitivity to study intervention(s) or related products.
2. 2. Current or previous participation (dosing with active treatment) in a study for an investigational ATTR depleting drug or ATTR gene editing therapy.
3. 3. Total bilirubin >3 × upper limit of normal (ULN) at screening.
4. 4. Current diagnosis or history of amyloid light chain, other non-ATTR amyloidosis or known leptomeningeal amyloidosis, or multiple myeloma.
5. 5. HF not primarily caused by ATTR-CM, for example, due to hypertension, valvular heart disease, or ischemic heart disease in the opinion of the investigator.
6. 6. Currently hospitalised or hospitalised within 14 days prior to screening.
7. 7. Currently treated with positive inotropic medication.
8. 8. Uncorrected, severe, haemodynamically significant, left-sided heart valve disease. Note: pre existing echocardiogram up to 2 years old may be used.
9. 9. Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularisation, cardiac device implantation, cardiac valve repair, or major surgery within 60 days of screening.
10. 10. Prior solid organ transplant or planned solid organ transplant during the study.
11. 11. Left ventricular ejection fraction (LVEF) <30% as assessed by centralised review of echocardiography.
12. 12. Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or carcinoma in situ/high-grade prostatic intraepithelial neoplasia (PIN), low-risk prostate cancer or on stable therapy for prostate cancer) within 3 years before screening.
13. 13. End stage renal disease (estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m2 at screening, or chronic/intermittent haemodialysis or peritoneal dialysis).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of occurrences of the composite endpoint consisting of: • CV death • Recurrent CV events (CV hospitalisation and urgent HF visits )

Secondary endpoints 7

1. Secondary Confirmatory: Change in KCCQ-CSS
2. Change in 6MWD
3. Number of occurrences of CV events (CV hospitalisation and urgent HF visits)
4. Time to occurrence of CV death
5. Time to occurrence of all-cause death
6. Time to first occurrence of composite CKD endpoint: • CV death • Onset of persistent decline eGFR ≥ 30% • Onset of persistent eGFR < 15 mL/min/1.73m2 • Initiation of chronic kidney replacement therapy (dialysis or kidney transplant)
7. Change in KCCQ-OSS

Investigational products

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

Test 1

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 4

Locations

8 EU/EEA countries · 97 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

Documents 143 files

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

Application history

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