Alpha-1 Antitrypsin (AAT) is a naturally occurring protein involved in the protection of lungs from inflammation. A mutation in the AAT gene (a change in the body's genetic instructions on how to make AAT) causes it to be made incorrectly and very little of it gets into the bloodstream. Severe AAT deficiency (lack of AAT in the blood) causes emphysema, which causes holes in the lungs. This study is being done to learn more about the safety and effectiveness of VX-864 in patients with Alpha-1 Antitrypsin Deficiency.
The treatment period is 28 days with 3 additional follow-up visits. Participants will be randomized to one of 4 groups. Randomized means there is an equal chance of being placed in any of the 4 groups. The groups are placebo (no active drug) or treatment groups 1-3 with varying doses. All groups will take 5 tablets in the morning and 5 tablets at night. The treatment group will take either 100mg, 300mg, or 500mg tablets twice a day. There is an 80% chance of being assigned to a treatment group and a 20% chance of being assigned to placebo.
This research study will be evaluating whether liquid nitrogen sprayed on the cells lining the airways (cryotherapy) can reduce the mucus produced in the lungs of patients with chronic obstructive pulmonary disease (COPD). The study involves bronchoscopies, (placement of a lighted, flexible scope into the lungs) under general anesthesia to deliver the treatment to the lungs. The study is randomized such that 2/3 of individuals get the cryotherapy and the other 1/3 get a sham (control) treatment with no cryotherapy. Participants in the sham control group will be evaluated for eligible for cryotherapy at end of year one. The Study duration is 36 months. Those initially randomized to the treatment group, they will have 7 clinic visits and 2 treatment visits. Participants randomized to sham group will have 11 clinic visits and 4 treatment visits.
The primary purpose of this study is to see if the Targeted Lung Denervation (TLD) therapy (Active Treatment) is more effective than a sham procedure (Sham Control/no TLD therapy) at decreasing moderate or severe exacerbations in patients with COPD on optimal medical care. In addition, the study seeks to compare long-term safety, and other efficacy assessments, between the Active Treatment arm and the Sham Control arm.
TLD Therapy is done by passing a bronchoscope, with a special device (catheter) inserted through it, into the lungs. This special catheter delivers a type of electrical energy called radio frequency (or RF) energy to the nerves located on the outside of the airways. As with many bronchoscopic procedures, this is done while under anesthesia.
Participants will be randomly assigned (like flipping a coin) to receive one of two different treatments, either TLD Therapy in addition to optimal medical care (Active Treatment) or optimal medical care only (Sham Control). No matter which treatment you receive, you will undergo the same type of procedure, testing and follow-up while remaining on optimal medical care for COPD. You will have an equal chance of being assigned to either Active Treatment or the Sham Control group (1:1 randomization). Neither you or your study doctor will know which treatment you have received until after your 12-month follow-up visit. At the 12-month visit you will find out whether you received the active or sham procedure. If you received the sham procedure you have the option of crossing over into the treatment group and receiving TLD therapy.
Participation in the study will last for approximately 62 months. Depending on which group you are randomized to and if you decide to crossover to the treatment group, there will be 1-2 visits for TLD Therapy or sham control (non-active) procedure, 9-12 in-person clinic visits, and 13-23 phone visits.
Alpha-1 antitrypsin (Alpha-1, AAT) deficiency is an inherited disease which results from a defect in the alpha-1 gene. Severe AAT deficiency causes emphysema predominant chronic obstructive pulmonary disease (COPD). This study is designed to test the effectiveness of an drug (Alvelestat) on lung damage caused by Alpha-1 Antitrypsin Deficiency. This is blinded study and there is a 50% chance of receiving a placebo.
Alpha-1 Antitrypsin (AAT) is a naturally occurring protein involved in the protection of lungs from inflammation. A mutation in the AAT gene (a change in the body's genetic instructions on how to make AAT) causes it to be made incorrectly and very little of it gets into the bloodstream.This results
in the lung damage known as emphysema. ARO-AAT is an investigational drug, which means that it is not approved by the Food and Drug Administration. ARO-AAT works by interrupting a step in the production of AAT. In a patient with AATD, this would stop the mutated protein from being made. This study is being carried out to see how safe and well tolerated ARO-AAT is, and to see if low, medium and high doses of the study treatment will decrease Alpha-1 Antitrypsin in the blood and in the liver compared to a placebo, or dummy injection. The Study medication is given via injection on Day 1, 29 and 133 and then every 84 days. The study includes approximately 17 visits over a period of 24 month. Compensation will be provided for study site visits. .
Lymphangioleiomyomatosis (LAM) is a rare lung disease that is caused by genetic mutations. It results in the uncontrolled growth and proliferation of an atypical smooth muscle cells in the lung. These cells invade airways, blood vessels, and lymph vessels, and limit the flow of air, blood, and lymph, respectively. The source of the cells is unknown, but available evidence indicates they arise from an extrapulmonary source. Their aberrant behavior is due to mutations in tuberous sclerosis genes that results in mTOR activation. Respiratory failure, lung collapse (pneumothorax), and pleural effusions (chylothorax) are hallmarks of the disease. This study will evaluate the safety and durability of the mTOR inhibitors sirolimus and everolimus, which are FDA approved medications for prevention of rejection of transplanted organs, in stabilizing or improving lung function in people in LAM.
The purpose of the MUSC Pulmonary Biorepository is to collect and store samples linked to medical and other informa¬tion from individuals with pulmonary disease as well as healthy controls.
In combination with the clinical data and other approved research studies (that may recruit for and/or utilize samples of the biorepository) this sample repository will provide for uniform, longitudinal, complete and accurate data that can be organized and clinically correlated at the time of sample donation, with longitudinal testing possible as part of future study. Samples will be linked to each participant's unique ID, though will be deidentified and coded for use in future research and subsequent publications with pulmonary disease and control patients.