Alpha-1 Antitrypsin Deficiency

Researchers are studying adults with Alpha-1 Antitrypsin Deficiency (AATD), a genetic condition that can cause liver problems, to understand how these liver issues develop and change over five years without treatment. The study also aims to identify factors that predict when liver disease may begin or improve, describe how the condition is diagnosed and managed in normal hospital care, and assess how AATD affects lung function in adults. Participants diagnosed with specific AATD types—either homozygous Pi*ZZ with mild or no liver disease, or heterozygous Pi*SZ with moderate to severe liver disease—will be followed. Data will be collected during routine care visits over the study period. No treatment is given as part of the study since it is observational, focusing on monitoring and collecting health data. During the study, participants will provide medical history including dates of diagnosis and liver or lung problems. They will complete yearly questionnaires about their health for up to five years. Researchers will track outcomes such as liver disease progression or regression, lung disease development, and mortality causes. The study helps improve understanding of AATD and its effects, with data collected through regular clinical care and patient reports.

Researchers are studying KB408, a specially designed inhaled gene therapy using a non-replicating herpes simplex virus vector to deliver functional human SERPINA1 gene to the lungs of adults with alpha-1 antitrypsin deficiency (AATD). This trial targets adults aged 18 to 70 with specific genetic forms of AATD (PI*ZZ or PI*ZNull) to evaluate safety and how the treatment affects biological markers related to the disease. The study is a Phase 1 trial conducted by Krystal Biotech, Inc. to assess initial safety and pharmacodynamics of KB408. The study involves four groups: three single-dose groups receiving low, mid, or high doses of nebulized KB408, and one group receiving multiple doses at the mid-level dose. Participants receiving intravenous augmentation therapy must pause this treatment for at least 10 days before and during the repeat dose and high-dose groups. The investigational drug, KB408, is administered via nebulization to deliver the gene therapy directly to the airways. Participants will be monitored closely for safety over 2 to 3 months, including tracking adverse events, vital signs, lung function tests, ECGs, and laboratory tests. Researchers will also measure levels of alpha-1 antitrypsin and neutrophil elastase in blood and lungs to understand the treatment's biological effects. The study observes participants for changes from baseline to evaluate tolerability and pharmacodynamics of KB408 during and after dosing.

Researchers are evaluating BEAM-302, a lipid nanoparticle-based therapy, in adults with Alpha-1 Antitrypsin Deficiency (AATD) associated lung and/or liver disease. This Phase 1/2 study aims to assess the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and efficacy of BEAM-302 while determining the optimal biological dose (OBD) in this patient population. The study includes two parts: Phase 1 dose exploration and Phase 2 dose expansion. Participants will receive BEAM-302 to evaluate various doses for safety and biological effects. Those currently on augmentation therapy in certain regions must stop for at least six weeks before joining unless clinically necessary. The study assesses lung function, liver fibrosis, and blood levels of alpha-1 antitrypsin over a two-year period. Participants will undergo lung function tests, liver assessments including biopsies or scans, and genetic confirmation of AATD. Researchers will monitor treatment-emergent adverse events and measure blood alpha-1 antitrypsin levels for up to two years. This long-term monitoring helps understand the treatment's impact and safety in adults aged 18 to 70 with confirmed AATD and specific lung or liver disease criteria.

Researchers are gathering data on individuals diagnosed with Alpha-1 Antitrypsin Deficiency (Alpha-1) and those identified as Alpha-1 carriers to support research and development of better treatments and a cure. This observational study aims to create a confidential, organized database with complete and accurate long-term information to help investigators conduct studies and improve understanding of disease progression. Participants include both people diagnosed with Alpha-1 and those who carry the gene. The registry collects regular updates from members over time to provide objective data points. This larger group of patients will help support upcoming clinical trials planned over the next several years. Participants provide ongoing information about their condition, which researchers use to measure disease progression. The primary goal is to establish the Alpha-1 Research Registry within two years using a secure data system. The study runs until June 2029, with no treatments assigned, focusing on observation and data collection to benefit the broader Alpha-1 community.

Alpha-1-antitrypsin deficiency is a common inherited disease affecting the respiratory system, often causing early lung problems such as emphysema or bronchiectasis. This condition can also lead to liver cirrhosis, vasculitis, and other organ disorders. The disease progresses rapidly, especially in patients with COPD, and affects younger people with a faster loss of lung tissue. The Czech AATD Registry is a non-interventional study designed to collect and analyze clinical data from patients with this genetic disorder to better understand its impact and raise awareness. The registry is a multicenter, retrospective and prospective longitudinal follow-up study of patients with alpha-1-antitrypsin deficiency. It includes patients with severe or rare forms of the deficiency, regardless of age or organ involvement. The study gathers data without introducing any treatments, providing a comprehensive view of the disease within the Czech population. Participants provide clinical information that researchers use to monitor lung function, exercise tolerance, respiratory function, and quality of life over time. The study also evaluates lung CT densitometry to better define COPD phenotypes related to AAT deficiency and tracks liver and other organ disorders. Follow-up assessments occur within one year after study completion, supporting ongoing understanding of disease progression and patient outcomes.

This observational study aims to collect clinical information on the safety and performance of the NEXUS Aortic Arch Stent Graft System and the Custom-Made NEXUS DUO Aortic Arch Stent Graft System for treating aortic aneurysms. The main questions focus on early mortality, safety outcomes, device failure, and procedural and hospitalization details. Participants are treated according to standard care at their institutions. Participants receive treatment per their institution's standard of care using either the NEXUS Aortic Arch Stent Graft System or the custom-made NEXUS DUO Aortic Arch Stent Graft System. The study includes both prospective and retrospective data collection with two groups based on the device used. Follow-up information is collected for up to five years after treatment. During the study, researchers will gather data on mortality at 30 days and 12 months, major adverse events, device failure, and other safety outcomes. Participants will undergo regular follow-up visits to monitor these outcomes and collect hospitalization and procedural information. The study is designed to observe real-world use of these devices and understand their longer-term safety and performance.

Researchers are evaluating a gene therapy called AAV8hAAT(AVL) to treat alpha 1-antitrypsin (AAT) deficiency. This condition affects the lungs due to a deficiency of the AAT protein. The study aims to deliver a single intravenous dose of this gene therapy, which codes for an oxidation-resistant form of the AAT protein, to see if it can safely and effectively protect the lungs over time. Participants will receive different doses of the gene therapy, with groups receiving varying amounts of vector genome copies per kilogram of body weight. The study is non-randomized and open-label, with no placebo group. The treatment is given as a one-time intravenous infusion, and researchers will observe the participants for safety, toxicity, and dosage tolerance over approximately two years. During the study, participants will undergo various assessments including blood tests to measure AAT levels in serum and lung fluid at multiple time points up to five years. Safety will be monitored by tracking serious adverse events and dose-limiting toxicities. Lung function will be evaluated by imaging and clinical tests. The total participation may last several years to gather long-term data on the gene therapy's effects and safety.

Researchers are investigating how Alpha-1-antitrypsin (AAT) deficiency and Cystic Fibrosis (CF), both genetic disorders, affect lung white blood cells called macrophages and their ability to respond to inflammation. AAT deficiency affects many people with chronic obstructive pulmonary disease (COPD) and may cause disease progression due to malfunctioning macrophages. CF causes lung tissue inflammation, and macrophages have a key role in both causing and resolving this inflammation. Participants are grouped into three categories: those with AAT deficiency, those with CF carrying the Delta F508 mutation, and those without lung disease. At each study visit, all participants undergo a history and physical exam, blood draws, and lung function tests involving forceful breathing before and after using an Albuterol inhaler. The inhaler is used as part of the pulmonary function testing with at least a 30-minute wait between inhaler use and the second lung test. During the study, researchers evaluate lung macrophage function, blood levels of alpha-1 antitrypsin and an inflammatory marker called C-reactive protein, and lung function. These assessments are done on average within 30 days after sample collection or testing. Participants' medical history, physical exams, and lung testing are repeated at each visit to monitor changes and understand how these diseases impact lung immune response and inflammation.

This research aims to find out if inhaling Alpha 1-Antitrypsin (AAT) daily at a dose of 80 mg can slow down lung disease progression in people with lung problems caused by severe genetic Alpha 1 Antitrypsin Deficiency (AATD). The study is a Phase 3 trial comparing the inhaled AAT treatment to a placebo. It evaluates lung function using tests such as spirometry and CT scans to measure lung density and overall lung health. Participants will inhale either the study drug Kamada AAT or a placebo solution every day for two years during the double-blind phase. After this, all participants receive the active AAT treatment for an additional two years in an open-label extension. The treatment is given using a nebulizer device, and participants are asked to maintain daily cleaning of the device and record symptoms and drug use in an electronic diary. Throughout the study, participants will attend clinic visits: 11 visits during the first two years and 5-6 visits during the extension phase. After treatment ends, there will be three follow-up clinic visits over six months. Researchers will perform lung function tests, CT scans, six-minute walk tests, quality of life questionnaires, and biomarker assessments. The primary outcome measured is lung function (FEV1) after bronchodilator use at 104 weeks to understand the treatment's impact on lung disease progression.

Researchers are studying lung disease progression in people with Alpha-1 Anti-trypsin Deficiency (AATD), focusing on those with the PiMZ genotype. This genetic condition can cause lung and liver problems, and its effects vary among individuals. The goal is to find early signs in lung scans and blood or sputum tests that predict worsening lung disease in these patients, as traditional lung function tests may not always reflect disease progression accurately. The study follows a group of PiMZ patients with obstructive lung disease over three years. Participants will undergo detailed lung imaging using high-resolution CT scans at the start and again at 18 and 36 months. Blood and sputum samples will be collected to measure various biomarkers. Participants also complete questionnaires about their lung health, including monthly surveys about exacerbations. These procedures help researchers track changes in lung density and other markers over time. Participants will have their medical and medication histories reviewed and perform lung function tests such as spirometry at each visit. The study will assess changes in lung density and lung function decline, using CT imaging and biomarker data to identify early signs of worsening emphysema. The total study duration for each participant is three years, with regular follow-ups to monitor lung health and disease progression.