NNC6019-0001 for Transthyretin Amyloid Cardiomyopathy

Recruiting in Palo Alto (17 mi)

+30 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Novo Nordisk A/S

Must not be taking: Calcium channel blockers

Disqualifiers: Organ transplant, Malignant neoplasm, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

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}

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.

Trial 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 (Other)

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

NW Univ-Bluhm Cardiovasc Inst Chicago, IL

Cedars-Sinai Medical Center_Los Angeles Los Angeles, CA

University of Calgary_Cardiology Calgary, Canada

Ctr for Cardiovascular Innovation Vancouver, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Novo Nordisk A/S Lead Sponsor

References

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

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy. [2020] Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0).

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

Vutrisiran: A Review in Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis. [2023] Silencing the transthyretin (TTR) gene is an effective strategy in the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis. Vutrisiran (Amvuttra®), an RNA interference (RNAi) therapeutic targeting TTR mRNA, is approved in the USA and EU for the treatment of adults with polyneuropathy of hATTR amyloidosis. N-acetylgalactosamine conjugation and enhanced stabilisation chemistry are utilised to target vutrisiran to the liver and increase stability, respectively, allowing for subcutaneous administration once every 3 months. In a pivotal phase 3 study in patients with hATTR amyloidosis with polyneuropathy, subcutaneous vutrisiran 25 mg every 3 months significantly reduced neuropathy impairment versus external placebo. Vutrisiran was also associated with significant improvements in neuropathy-specific quality of life, gait speed, nutritional status and disability scores. Vutrisiran was generally well tolerated; the only common adverse events to occur at a greater incidence than with external placebo were pain in extremity and arthralgia. Vutrisiran reduces serum vitamin A levels and vitamin A supplementation is recommended. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, which has the potential advantage of infrequent subcutaneous dosage.

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] Currently, the most used peptide receptor radionuclide therapy (PRRT) regimen for neuroendocrine tumors comprises 4 treatment cycles, and there is not enough large-scale data to support the safety of more individualized extended PRRT. This study aims to evaluate the therapeutic effectiveness and potential nephrotoxicity related to PRRT using more than four treatment cycles.

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] Peptide receptor radionuclide therapy (PRRT) is routinely used for advanced or metastasized neuroendocrine tumours (NET). To prevent nephrotoxicity, positively charged amino acids (AA) are co-infused. The aim of this study was to correlate the risk for therapy-related hyperkalaemia with the total amount of AA infused.

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

Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies. [2022] Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting radiopharmaceutical into the circulation of a patient. The radiopharmaceutical will bind to a specific peptide receptor leading to tumor-specific binding and retention. The only target that is currently used in clinical practice is the somatostatin receptor (SSTR), which is overexpressed on a range of tumor cells, including neuroendocrine tumors and neural-crest derived tumors. Academia played an important role in the development of PRRT, which has led to heterogeneous literature over the last two decades, as no standard radiopharmaceutical or regimen has been available for a long time. This review provides a summary of the treatment efficacy (e.g., response rates and symptom-relief), impact on patient outcome and toxicity profile of PRRT performed with different generations of SSTR-targeting radiopharmaceuticals, including the landmark randomized-controlled trial NETTER-1. In addition, multiple optimization strategies for PRRT are discussed, i.e., the dose-effect concept, dosimetry, combination therapies (i.e., tandem/duo PRRT, chemoPRRT, targeted molecular therapy, somatostatin analogues and radiosensitizers), new radiopharmaceuticals (i.e., SSTR-antagonists, Evans-blue containing vector molecules and alpha-emitters), administration route (intra-arterial versus intravenous) and response prediction via molecular testing or imaging. The evolution and continuous refinement of PRRT resulted in many lessons for the future development of radionuclide therapy aimed at other targets and tumor types.