The purpose of this study is to evaluate the safety and effectiveness of acoramidis (AG-10) and determine if it can help people with the genetic TTR variant that can cause ATTR-CM. The sponsor (Eidos) is conducting a research study to see if the study medicine will help in slowing the development and/or progression of a rare disease called Symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM). AG-10 is an investigational drug. "Investigational" means that AG-10 is not yet approved for use in any settings outside of clinical research studies like this one and is considered experimental. Cardiomyopathy is a disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body. AG-10 has been shown to reduce the level of TTR in the blood of animals and healthy volunteers tested to date. Reducing the amount of TTR in your blood may reduce the amount of amyloid deposits in your body and may keep your cardiomyopathy from getting worse over time.

If you meet the requirements and agree to participate in this study, you will go through a 2 part screening period and if approved you will begin treatment. You will be randomized, like flipping a coin, to drug or placebo and take two pills once every day for 60 months.
Your participation in this study will last up to 60 month and will consist of clinic visits and follow up visits at home via the telephone. Some tests requires of you will include an echo, ECG, cardioradionuclide scans (scans that use radioactive agents to look at images of the heart like a PET scan), MRIs, blood tests, nerve conduction test, urine samples, and skin biopsies.

This study involves an investigational drug called ALXN2220 for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). Investigational means it is not yet approved for commercial use or sale by the Food and Drug Administration (FDA). ALXN2220 is intended to promote the elimination of ATTR deposits leading to symptom improvement.
All participants will be randomized, meaning assigned by chance, to receive ALXN2220 or placebo. A placebo looks like the study drug but contains no active medication. In this study, participants will have a 2 out of 3 chance, like drawing straws, of receiving the study drug and 1 out of 3 chance of receiving placebo. Neither the participants nor the study team or study doctor will know if they are assigned to receive the study drug or placebo. The study drug or placebo will be administered intravenously (IV), meaning into a vein in the arm, every four weeks.
Participation in this study will include a maximum of 56 visits over a maximum of 48 months. Study procedures include collection of vital signs, study drug infusion, physical exams, 12-lead electrocardiography, blood and urine collection, echocardiogram (ultrasound test of the heart), questionnaires, and some optional testing.

This study is for those with Transthyretin (TTR) Amyloidosis with Cardiomyopathy or ATTR-CM. ATTR-CM is a condition where the heart muscle does not pump your blood through your body as it should because of build up of abnormal protein between the muscle fibers in your heart. The specific protein is called transthyretin amyloid (TTR). The study involves an investigational drug called NTLA-2001. Investigational means it is not approved for commercial sale or use by the Food and Drug Administration. This study is a randomized study meaning participants will be assigned by chance to receive NTLA-2001 or placebo. A placebo looks like the investigational drug but contains no active ingredient. In this study, two out of three participants are assigned to receive NTLA-2001 and one out of three will receive placebo. NTLA-2001 or placebo are given by intravenous (IV) infusion meaning in your vein.

NTLA-2001 consists of a gene editing system which can "knockout" the TTR gene and permanently change the DNA (deoxyribonucleic acid, which contains information that determines parts in traits such as eye color or height, that are passed on from parent to child) so the gene stops making the TTR protein.

This study will last at least 18 months and include up to 17 visits. Study related procedures include physical exams, blood work including genetic testing, eye exam, hall walk test, electrocardiograms (ECGs), echocardiogram (echo) and vitamin A supplement. Study risks include infusion related risks like headache, fever, chills, or increased liver enzymes. Other study related risks include genetic risks, loss of confidentiality and unknown risks.