Alpha-1 Antitrypsin Deficiency

Alpha-1 Antitrypsin Deficiency AATD occurs when the liver produces an abnormal protein called Z-AAT, which builds up in liver cells and causes low blood levels of AAT. This study focuses on adults with AATD to learn about the natural progression of liver problems caused by this condition over 4 to 8 years. The research also aims to identify factors that predict changes in liver disease, describe how the condition is diagnosed and monitored in usual care, and assess its impact on lung function. Participants include adults diagnosed with either the AATD-Pi*ZZ genotypephenotype with or without liver disease, or the AATD-Pi*SZ genotypephenotype with moderate to severe liver disease. This is an observational study where data is collected prospectively during routine care. No experimental treatment is given. Participants are followed over several years to gather information about their liver and lung health, with data collected according to standard medical practice. During the study, participants provide medical history including the date of AATD diagnosis and any liver or lung problems. Questionnaires about symptoms and quality of life are completed at the start and yearly thereafter until the study ends. Researchers track liver disease progression, regression, mortality, and lung disease development or worsening. Data collection spans up to 8 years, with ongoing monitoring to understand the disease course and current clinical practices.

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 treatments 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 andor liver disease. This Phase 12 study aims to assess the safety, tolerability, pharmacokineticspharmacodynamics PKPD, 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 treatments 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.

Researchers are studying emphysema caused by alpha-1-antitrypsin deficiency AATD, a rare genetic condition that can lead to serious outcomes like lung transplantation or death in up to 15% of patients. The study aims to create a prediction tool combining clinical, biological, functional, and advanced lung CT imaging data to identify patients at higher risk, helping to improve care and resource use. The study is observational and will collect data retrospectively from patients diagnosed between 2010 and 2025 with emphysema and COPD secondary to specific AATD mutations. Data includes clinical measures like BMI and dyspnea scores, respiratory function tests, and quantitative CT imaging including radiomics. Results will be validated using an external European database. The goal is to better anticipate transplant needs and optimize treatment decisions, including the use of costly intravenous alpha-1 antitrypsin therapy. Participants usual care data will be collected from medical records, including CT scans and lung function tests taken within a year of diagnosis. The main outcomes measured are survival status and lung transplantation status over a 5-year period. This approach aims to support personalized care and guide health policy to improve treatment access for those most at risk. The study is set to run from February 2026 through March 2031.

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 institutions 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 AAV8hAATAVL 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 therapys 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.

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.