NNC6019-0001 for Transthyretin Amyloid Cardiomyopathy

Not currently recruiting at 37 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novo Nordisk A/S

Must not be taking: Calcium channel blockers

Disqualifiers: Organ transplant, Malignant neoplasm, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 140 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine called NNC6019-0001 (also known as Coramitug, NN-6019, or PRX-004) for individuals with heart disease caused by TTR amyloidosis, a condition that can lead to heart failure. The trial aims to determine the long-term safety of this medicine and its effectiveness in reducing heart disease symptoms. Participants who completed an earlier study with this medicine are invited to join, provided they have finished the previous study and are on stable heart medications. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stay on stable doses of your current heart-related medications for at least 6 weeks before joining. However, you cannot take certain calcium channel blockers like verapamil or diltiazem, unless they are dihydropyridine types, and digoxin is only allowed if needed for specific heart conditions.

Is there any evidence suggesting that NNC6019-0001 is likely to be safe for humans?

Research shows that NNC6019-0001 is undergoing safety testing in people with transthyretin amyloid cardiomyopathy, a type of heart disease. In earlier studies, patients received this treatment to assess its potential benefits for heart problems. The results suggested it was generally well-tolerated.

While exact details on side effects aren't always available, progression to later research stages often indicates promising earlier results. This trial aims to further explore its long-term safety and effectiveness. Prospective participants should note that ongoing research suggests a reasonable level of safety so far, but discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for transthyretin amyloid cardiomyopathy (ATTR-CM), which often include medications like tafamidis or diflunisal that stabilize the transthyretin protein, NNC6019-0001 introduces a novel approach. This experimental treatment is administered intravenously every four weeks and targets the disease by potentially breaking down the amyloid deposits directly. Researchers are excited about NNC6019-0001 because it offers a new mechanism of action that could complement or enhance current therapies, providing hope for improved outcomes in managing ATTR-CM.

What evidence suggests that NNC6019-0001 might be an effective treatment for transthyretin amyloid cardiomyopathy?

Research has shown that NNC6019-0001 might help treat transthyretin amyloid cardiomyopathy, a heart disease caused by protein buildup. Early findings suggest it could lower the risk of heart-related death and illness in affected individuals. This treatment targets the harmful protein buildups in the heart. Although more data is needed, the early results are promising for those with this condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for people who have heart failure due to Transthyretin Amyloidosis and were part of a previous study on the medicine NNC6019-0001. Only those who completed the initial study can join this long-term research to further assess safety and effectiveness.

Inclusion Criteria

Completed study intervention in NN6019-4940 and attended the last study visit (week 64; visit 16), and no later than 12 weeks after visit 16

I have been on a stable heart medication dose for 6 weeks.

Exclusion Criteria

I haven't had cancer, except for certain types, in the last 5 years.

I am currently taking specific heart medications, but not those that mainly affect blood pressure.

My body weight is over 120 kg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NNC6019-0001 intravenously every 4 weeks added to the standard of care

140 weeks

Intravenous administration every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

17 weeks

Open-label extension

Participants continue to receive NNC6019-0001 for long-term safety and efficacy assessment

157 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NNC6019-0001

Trial Overview The trial is testing NNC6019-0001, focusing on its long-term safety and ability to alleviate symptoms of heart disease caused by TTR amyloidosis. Participants will receive NNC6019-0001 for up to 157 weeks, regardless of their prior treatment group.

How Is the Trial Designed?

Group I: NNC6019-0001 Experimental Treatment 1 Intervention

Participants will receive NNC6019-0001 intravenously every 4 weeks added to the standard of care until Week 140.

NNC6019-0001 is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Coramitug for:

• Transthyretin amyloid cardiomyopathy (ATTR-CM)

Approved in United States as Coramitug for:

• Transthyretin amyloid cardiomyopathy (ATTR-CM)

Approved in Japan as Coramitug for:

• Transthyretin amyloid cardiomyopathy (ATTR-CM)

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

In a study of 637 patients, those receiving more than four cycles of peptide receptor radionuclide therapy (PRRT) showed significantly improved overall survival (72.8 months) compared to those receiving the standard four cycles (52.8 months), indicating that extended treatment may enhance therapeutic effectiveness.

The study found no significant increase in nephrotoxicity between the standard and extended treatment groups, suggesting that extending PRRT beyond four cycles is safe for renal function, with adverse renal events occurring in only 0.4% of the standard group and 1.1% of the extended group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended peptide receptor radionuclide therapy: evaluating nephrotoxicity and therapeutic effectiveness in neuroendocrine tumor patients receiving more than four treatment cycles. Baum, RP., Fan, X., Jakobsson, V., et al.[2023]

Peptide receptor radionuclide therapy (PRRT) effectively targets tumors by using radiopharmaceuticals that bind to somatostatin receptors, which are overexpressed in neuroendocrine tumors, leading to tumor-specific treatment and symptom relief.

The review highlights the importance of optimizing PRRT through various strategies, including dose adjustments, combination therapies, and new radiopharmaceuticals, which can enhance treatment efficacy and patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies. Ahmadi Bidakhvidi, N., Goffin, K., Dekervel, J., et al.[2022]

In a study of 38 patients undergoing peptide receptor radionuclide therapy (PRRT) for advanced neuroendocrine tumors, hyperkalemia (HK) occurred in 94.7% of patients within 4 hours of amino acid co-infusion, with 36.1% experiencing severe HK (>6.0 mmol/l).

A combination of serum parameters, particularly a baseline blood urea nitrogen (BUN) level greater than 28 mg/dl, was found to effectively predict severe hyperkalemia with an accuracy of 81.6%, helping to identify patients at higher risk during PRRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy. Lapa, C., Werner, RA., Bluemel, C., et al.[2020]

Vutrisiran, an RNA interference therapy targeting the TTR gene, has been shown to significantly reduce neuropathy impairment in patients with hereditary transthyretin-mediated amyloidosis, based on a pivotal phase 3 study.

The treatment is generally well tolerated, with the main side effects being pain in extremities and arthralgia, and it offers the convenience of subcutaneous administration every three months, making it a practical option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vutrisiran: A Review in Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis. Nie, T., Heo, YA., Shirley, M.[2023]

In a study of 22 patients undergoing peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors, 91% experienced self-limiting hyperkalaemia (high potassium levels) after amino acid co-infusion, indicating this is a common side effect.

Changing the amount of co-infused amino acids (75g vs. 50g) did not affect the incidence or severity of hyperkalaemia, suggesting that the risk of this side effect is inherent to the therapy rather than the amino acid dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of the amount of co-infused amino acids on post-therapeutic potassium levels in peptide receptor radionuclide therapy. Lapa, C., Werner, RA., Bluemel, C., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07207811

NCT07207811 | CLEOPATTRA: A Research Study to Look ... This study will find out if a new medicine called NNC6019-0001 can help reduce the risk of heart-related death and illness in participants with a condition ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06260709

NCT06260709 | A Research Study to Look at Long-term ... This study will test a medicine, NNC6019-0001, for people who have a heart disease due to TTR amyloidosis. It will look at how safe this medicine is in the long ...

3. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/NN6019-4940

ATTR CM: Efficacy and Safety of NNC6019-0001 in ... The purpose of this study is to determine whether an investigational drug called NNC6019-0001 can be used to treat people with transthyretin (TTR)

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12379670/

Current and Future Treatment Landscape of Transthyretin ... This review summarizes available and investigational therapies for ATTR-CM and considers practical questions that guide clinical decision-making ...

5. cardionerds.com cardionerds.com/424-treatment-of-transthyretin-amyloid-cardiomyopathy-attr-cm-with-dr-justin-grodin/

424. Treatment of Transthyretin Amyloid Cardiomyopathy ... Outcomes: improve morbidity and mortality ... Agents that clear amyloid deposits are still in clinical trials (ALXN2200, Coramitug PRX004).

6. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/NN6019-7565

Long-Term Safety and Efficacy of NNC6019-0001 in ... The purpose of this study is to evaluate the long-term safety and effectiveness of a medicine called NNC6019-0001 in people who have heart failure.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39472768/

PRX004 in variant amyloid transthyretin (ATTRv) amyloidosis PRX004 was well tolerated in patients with ATTRv amyloidosis and demonstrated potential clinical activity. A phase 2 randomised controlled ...

8. academic.oup.com academic.oup.com/eurheartj/article/43/Supplement_2/ehac544.1767/6745267

NNC6019–0001, a humanized monoclonal antibody, in ... This is a randomized, double-blind, placebo-controlled trial recruiting 99 patients with hereditary or wild-type ATTR-CM.