NNC6019-0001 for Transthyretin Amyloid Cardiomyopathy

Recruiting at 30 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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

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 term and if it can reduce symptoms of a heart disease due to TTR amyloidosis, such as heart failure. It is an extension to a study called "A research study to look at how a new medicine called NNC6019-0001 works and how safe it is for people who have a heart disease due to TTR amyloidosis". Only participants who have completed that study will be invited for this new study. Participants will get NNC6019-0001, regardless of whether they got placebo or NNC6019-0001 in the first study. The study will last for up to 157 weeks (36 months/3 years).

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.

What data supports the effectiveness of the drug NNC6019-0001, Coramitug, NN-6019, PRX-004 for Transthyretin Amyloid Cardiomyopathy?

The research on vutrisiran, a drug that also targets the transthyretin (TTR) gene, shows that silencing this gene is effective in treating hereditary transthyretin-mediated amyloidosis, which is related to the condition targeted by NNC6019-0001. Vutrisiran significantly improved symptoms and quality of life in patients, suggesting that targeting TTR can be beneficial. ^{1 2 3 4 5}

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

3. 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]

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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