This study is enrolling participants with symptomatic ATTR-CM (transthyretin amyloidosis cardiomyopathy). ATTR-CM is a rare and serious disease that occurs when a protein in the blood called transthyretin (TTR) builds up throughout the body, including in the heart and nerves. When the abnormal protein, known as amyloid, deposits in the heart, the heart muscle thickens and stiffens, causing the heart to fail. This research study is designed to test whether the medication nucresiran is safe and helps people with ATTR-CM, in comparison to the effects of placebo.

Nucresiran is considered investigational, meaning it is not currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of ATTR-CM. Nucresiran is a TTR silencer. It is like a "quiet button" that turns down the amount of the disease-causing protein that is made. Because there is less TTR, there may be less buildup in the heart and other organs over time.

This is a randomized study meaning once eligibility is confirmed, participants will be assigned by chance, like drawing straws, to either receive nucresiran or placebo. You will have a 2 out of 3 chance of being assigned to nucresiran and a 1 out of 3 chance of being assigned placebo. Placebo is a substance that looks like the actual medication and is given the same way but contains no active substance. The study drug, which can be either nucresiran or placebo, will be given as an injection under the skin in the abdomen (avoiding the area around the navel), thigh, or the side or back of the upper arms. Neither the participants nor the study doctor will know who is assigned to nucresiran or placebo but this information can be made available if need be.

Participation in this study is expected to last for 5-8 years, Study related procedures include physical exams, vital signs, echocardiograms (ultrasound test of the heart), electrocardiograms, (ECG, a tracing of the heart's electrical activity), blood work, urine samples and questionnaires. Participants will also take Vitamin A daily. Study related risks include risks related to the study drug including injection site reactions, abnormal liver function or an allergic reaction. There may be risks related to study procedures including loss of confidentiality. There may not be any direct benefit, but the information learned may benefit others with ATTR-CM in the future.

This phase III trial compares durvalumab to the usual approach (patient observation) after surgery for the treatment of patients with early-stage non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The usual approach for patients who are not in a study is to closely watch a patient's condition after surgery and to have regular visits with their doctor to watch for signs of the cancer coming back. Usually, patients do not receive further treatment unless the cancer returns. This study will help determine whether this different approach with durvalumab is better, the same, or worse than the usual approach of observation. Giving durvalumab may help patients live longer and prevent early-stage non-small cell lung cancer from coming back as compared to the usual approach.