NNC6019-0001 for Transthyretin Amyloid Cardiomyopathy

No longer recruiting at 70 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novo Nordisk A/S

Must be taking: Cardiovascular therapy

Must not be taking: Calcium channel blockers

Disqualifiers: Non-ATTR cardiomyopathy, Organ transplant, Cancer, others

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

Compensation: Varies

Number of Visits: 16

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, NNC6019-0001 (also known as Coramitug, NN-6019, or PRX-004), for individuals with heart issues caused by transthyretin amyloid cardiomyopathy (ATTR CM). Researchers aim to determine if this medicine can reduce symptoms such as heart failure. Participants will receive either the new medicine or a placebo, with a higher likelihood of receiving the actual medicine. Ideal candidates for this trial are those diagnosed with ATTR CM, who are on stable heart medications, and do not have other types of heart disease. Participants will receive infusions every four weeks for about a year. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you be on stable doses of your heart medications for at least 6 weeks before starting. However, you cannot take certain calcium channel blockers like verapamil or diltiazem, but other types are allowed. If you take digoxin, it is only allowed if needed for specific heart rhythm issues.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NNC6019-0001, a new treatment for heart disease caused by TTR amyloidosis, has been tested in other studies. These studies indicate that patients generally tolerate the treatment well. For instance, participants in earlier trials of NNC6019-0001 did not report any major side effects. Additionally, another study is examining the long-term safety of this medicine and continues to monitor its effects on people with heart failure.

Although NNC6019-0001 is not yet approved for use, reaching this trial phase suggests that earlier trials did not find major safety issues. Patient safety remains a top priority, and ongoing studies continue to assess the treatment's safety for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for transthyretin amyloid cardiomyopathy, which often focus on stabilizing the transthyretin protein, NNC6019-0001 is designed to target and clear amyloid deposits directly from the heart. This unique mechanism could potentially address the root cause of the disease more effectively. Researchers are excited about NNC6019-0001 because it offers a novel approach that could improve heart function and quality of life for patients with this challenging condition. Additionally, NNC6019-0001 is administered through an intravenous infusion every four weeks, which could provide a more convenient treatment schedule compared to some existing therapies.

What evidence suggests that NNC6019-0001 might be an effective treatment for Transthyretin Amyloid Cardiomyopathy?

Research shows that NNC6019-0001 holds promise for treating transthyretin amyloid cardiomyopathy, a heart condition caused by protein buildup. Previous patients experienced fewer heart-related symptoms. In this trial, participants will receive either NNC6019-0001 at varying doses or a placebo. Studies suggest that NNC6019-0001 may reduce the risk of heart failure by targeting and removing harmful protein deposits in the heart. Although more information is needed, these findings indicate that NNC6019-0001 could effectively manage heart disease due to TTR amyloidosis. ^{1 5 6 7 8}

Who Is on the Research Team?

Clinical Transparency 2834

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with heart disease due to TTR amyloidosis, classified as NYHA Class II-III. They must have a specific diagnosis of ATTR CM, be on stable heart medication for 6 weeks prior, and meet certain lab test criteria. Exclusions include recent major cardiovascular events or surgeries, planned organ transplants, other types of cardiomyopathy, cancer history within 5 years, contrast allergies, and weight over 120 kg.

Inclusion Criteria

The thickness of a specific heart wall is greater than or equal to 12 millimeters.

My kidney function, measured by eGFR, is adequate.

My heart condition limits my physical activity but I can still perform light tasks.

Exclusion Criteria

You have had a bad reaction to a contrast dye or gadolinium in the past.

I am taking specific heart medications, but not those that majorly affect heart rhythm.

I have had cancer or was diagnosed with cancer in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of the study medicine or placebo every 4 weeks for 52 weeks

52 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• NNC6019-0001
• Placebo (NNC6019-0001)

Trial Overview The study tests NNC6019-0001's effectiveness in reducing symptoms of heart disease caused by TTR amyloidosis compared to a placebo. Participants are randomly assigned treatment: the chance of receiving NNC6019-0001 is twice that of getting the placebo. The drug is administered via infusion every four weeks for approximately 64 weeks.

How Is the Trial Designed?

Group I: NNC6019-0001, Dose 2 Experimental Treatment 1 Intervention

Participants will receive dose 2 i.v. infusion of NNC6019-0001 Q4W added to standard of care until week 52.

Group II: NNC6019-0001, Dose 1 Experimental Treatment 1 Intervention

Participants will receive dose 1 intravenous (i.v.) infusion of NNC6019-0001 every 4 weeks (Q4W) added to standard of care until week 52.

Group III: Placebo Placebo Group 1 Intervention

Participants will receive i.v. infusion of placebo (NNC6019-0001) Q4W added to standard of care until week 52.

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

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 22 patients undergoing endoradiotherapy (ERT), co-infusion of amino acids for kidney protection led to severe metabolic acidosis, which was associated with the development of hyperkalemia (high potassium levels).

The findings suggest that using bicarbonate solutions could be a simple and effective way to quickly correct the metabolic acidosis caused by amino acid co-infusion during ERT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperkalemia in patients treated with endoradiotherapy combined with amino acid infusion is associated with severe metabolic acidosis. Pfob, CH., Eiber, M., Luppa, P., et al.[2020]

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]

The newly developed [18F]AlF-NOTA-NT PET probe shows high receptor-binding affinity to neurotensin receptors (NTR1) and provides clear imaging of pancreatic tumors, indicating its potential for effective diagnosis of pancreatic ductal adenocarcinoma (PDAC).

This probe can be easily prepared using a straightforward chelation method, making it a promising tool for both detecting NTR1 positive tumors and facilitating personalized treatment strategies in pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of [18F]AlF-NOTA-NT as PET Agents of Neurotensin Receptor-1 Positive Pancreatic Cancer. Wang, M., Zhang, H., Wang, H., et al.[2019]

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 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]

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.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)

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06260709

NCT06260709 | A Research Study to Look at Long-term ... A Research Study to Look at Long-term Treatment With a Medicine Called NNC6019-0001 for People Who Have Heart Failure Due to Transthyretin Amyloidosis.

5. tandfonline.com tandfonline.com/doi/full/10.1080/13506129.2024.2420809

PRX004 in variant amyloid transthyretin (ATTRv) amyloidosis The results indicate that PRX004 may achieve anticipated therapeutic levels for binding to and clearance of TTR amyloid deposits in affected ...

6. 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 ...

7. 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.

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.