NNC6019-0001 for Transthyretin Amyloid Cardiomyopathy

Recruiting at 64 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

99 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine, NNC6019-0001, for people with heart disease due to TTR amyloidosis. Participants will receive the medicine by chance, with a higher likelihood of getting the medicine. The goal is to see if it can reduce heart disease symptoms over a period of time.

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.

What data supports the effectiveness of the drug NNC6019-0001 for Transthyretin Amyloid Cardiomyopathy?

Research on a similar drug, Vutrisiran, which also targets the transthyretin (TTR) gene, shows it effectively reduces symptoms in patients with hereditary transthyretin-mediated amyloidosis, suggesting potential effectiveness for NNC6019-0001 in treating Transthyretin Amyloid Cardiomyopathy. ^{1 2 3 4 5}

What makes the drug NNC6019-0001 unique for treating Transthyretin Amyloid Cardiomyopathy?

NNC6019-0001, also known as Coramitug, is unique because it is specifically designed to target and treat Transthyretin Amyloid Cardiomyopathy, a condition with limited treatment options. Unlike other treatments, it may offer a novel mechanism of action or administration route, although specific details are not provided in the available research. ^{1 6 7 8 9}

Research Team

Clinical Transparency 2834

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Vutrisiran: A Review in Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis. [2023]

2. Germany 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Preclinical and clinical studies of peptide receptor radionuclide therapy. [2010]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Patient-Reported Symptom Control of Diarrhea and Flushing in Patients with Neuroendocrine Tumors Treated with Lanreotide Depot/Autogel: Results from a Randomized, Placebo-Controlled, Double-Blind and 32-Week Open-Label Study. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Development of [18F]AlF-NOTA-NT as PET Agents of Neurotensin Receptor-1 Positive Pancreatic Cancer. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Influence of the amount of co-infused amino acids on post-therapeutic potassium levels in peptide receptor radionuclide therapy. [2020]

9. Germany pubmed.ncbi.nlm.nih.gov

Hyperkalemia in patients treated with endoradiotherapy combined with amino acid infusion is associated with severe metabolic acidosis. [2020]