What is the Purpose of this Study?
The purpose of this study is to understand how an experimental drug called NTLA-2001 affects a heart condition called transthyretin (TTR) amyloidosis with cardiomyopathy (ATTR-CM), a condition in which the heart muscle does not pump blood through the body as it should due to build-up of abnormal protein (TTR) between the muscle fibers in the heart. The study aims to determine whether NTLA-2001 is safe and effective in people with ATTR-CM.
NTLA-2001 uses a special gene-editing tool to change an individual’s DNA and turn off the TTR gene in liver cells. This stops the TTR gene from making the TTR protein, which may help improve the symptoms of ATTR-CM. (The process does not add any new permanent genetic material to the body; it just changes the way the patient’s DNA works to stop producing the harmful TTR protein.) Participants will be assigned to receive either NTLA-2001 or placebo (fluids that contain no active ingredients). For every 3 participants in the study, a computer will randomly choose 2 people to receive NTLA-2001 and 1 person to receive placebo. NTLA-2001 is designed to work only in the liver, where the TTR protein is made.
Eligibility
- * 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
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- * 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
- * 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:
- * 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.
- * 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.
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Where can I participate?
Beverly
More about this Clinical Trial
What is the full name of this clinical trial?
MAGNITUDE: A Phase 3, Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NTLA-2001 in Participants with Transthyretin Amyloidosis with Cardiomyopathy