Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2001 in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN) and Patients With Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM)

Launched by INTELLIA THERAPEUTICS · Oct 19, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called NTLA-2001 for patients with specific types of transthyretin amyloidosis (ATTR), a condition that can affect the nerves (polyneuropathy) or the heart (cardiomyopathy). The goal is to understand how safe the treatment is and how well it works in patients who might not have access to other approved therapies. The study is currently active but not recruiting new participants.

To be eligible for this trial, participants must be between 18 and 80 years old for polyneuropathy and up to 90 years old for cardiomyopathy. They should have a diagnosis of ATTR-related polyneuropathy or cardiomyopathy, weigh at least 45 kilograms, and have experienced symptoms such as heart failure. Participants will undergo various assessments during the study to monitor their health and response to the treatment. It’s important to note that individuals with certain other types of amyloidosis or specific heart conditions may not qualify. Overall, this study aims to explore a potential new option for managing these challenging conditions.

Gender

ALL

Eligibility criteria

• Polyneuropathy Inclusion Criteria:
• • Male and/or female participants 18 to 80 years of age inclusive, at the time of signing the informed consent
• • Diagnosis of polyneuropathy (PN) due to transthyretin (TTR) amyloidosis (ATTR)
• • Must have a body weight of at least 45 kilograms (kg) at Screening visit
• • Lack of access to approved treatments for ATTR and/or progression of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) despite use of approved treatment for ATTRv-PN
• Polyneuropathy Exclusion Criteria:
• • Amyloidosis attributable to non-TTR protein, e.g., amyloid light-chain (AL) amyloidosis
• • Known leptomeningeal transthyretin amyloidosis
• * Use of any of the following TTR-directed therapy for ATTR within certain timeframe:
• • 1. Patisiran
• • 2. Inotersen
• • 3. Vutrisiran
• • 4. Tafamidis
• • 5. Diflunisal
• • 6. Doxycycline and/or tauroursodeoxycholic acid
• 7. Any other investigational agent for the treatment of ATTRv-PN:
• • Other protocol defined Inclusion/Exclusion criteria may apply
• Cardiomyopathy Inclusion Criteria (UK only):
• • Male and/or female participants 18 to 90 years of age inclusive, at the time of signing the informed consent
• • Diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as hereditary ATTR amyloidosis with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy (ATTRwt-CM).
• • Must have a body weight of at least 45 kilograms (kg) at Screening visit
• • New York Heart Association (NYHA) Class I-III heart failure
• • At least 1 prior hospitalization for heart failure and/or clinical evidence of heart failure.
• • Able to complete ≥150 meters on the 6-minute walk test (6-MWT) during the Screening period.
• Cardiomyopathy Exclusion Criteria (UK only):
• • Amyloidosis attributable to non-TTR protein, e.g., amyloid light-chain (AL) amyloidosis
• • Known leptomeningeal transthyretin amyloidosis
• * Use of any of the following TTR-directed therapy for ATTR within certain timeframes:
• • 1. Patisiran
• • 2. Inotersen
• • 3. Vutrisiran
• • 4. Tafamidis
• • 5. Diflunisal
• • 6. Doxycycline and/or tauroursodeoxycholic acid
• • 7. Investigational TTR stabilizer (e.g., AG-10)
• • Participants with heart failure that in the opinion of the investigator is caused by ischemic heart disease, hypertension, or uncorrected valvular disease and not primarily due to transthyretin amyloid cardiomyopathy.
• • Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker is indicated but will not be placed. Pacemaker or defibrillator placement, initiation of or change in anti-arrhythmic medication within 28 days prior to study drug administration.
• • Other protocol defined Inclusion/Exclusion criteria may apply