68 Clinical Trials for Various Conditions
The investigators hypothesize that environmentally influenced histone modifications regulate AM mediated inflammation, contributing to a variable clinical course of AATD, and may also influence or be influenced by the activity of AAT augmentation therapy.
The purpose of this study is to evaluate the safety and tolerability of 72 milligrams per kilogram (mg/kg) and 180 mg/kg Alpha-1 15%, administered as a single-dose subcutaneous (SC) infusion and subsequently as weekly SC infusions over 8 weeks in participants with Alpha1-Antitrypsin Deficiency (AATD).
This is a study of gene therapy to treat alpha-1 antitrypsin deficiency. This study aims to treat AAT deficiency with a single administration of AAV8hAAT(AVL), a gene therapy that codes for an oxidation resistant form of the AAT protein, which if safe and if efficacious, will protect the lung on a persistent basis. We hope to learn the safety/toxicity and initial evidence of efficacy of intravenous delivery of this gene therapy to alpha 1-antitrypsin (AAT) deficient individuals.
The main aim of this study is to learn about liver problems caused by the lack of alpha-1 antitrypsin (called Alpha-1 Antitrypsin Deficiency or AATD) in adults when not treated (this is called the natural history of a condition) over 5 years. Other aims are to learn what can predict the AATD-liver condition starting and getting better or worse, describe how this condition is currently being diagnosed and watched in normal hospital care, and describe how the AATD also affects and adult's lung function. Data in this study will be collected to include medical history of a participant, including the date AATD was first identified and/or the date on which the first AATD-related liver or lung problems were diagnosed. At study start and then every year until study end, participants will be asked to completed questionnaires (called patient-reported outcomes or PRO).
The Sponsor is developing KB408, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector engineered to deliver functional full-length human SERPINA1 to the airways of people with alpha-1 antitrypsin deficiency (AATD) via nebulization. This study is designed to evaluate safety and pharmacodynamics of KB408 in adults with AATD with a PI\*ZZ or PI\*ZNull genotype. Three planned dose levels of KB408 will be evaluated in single dose escalation cohorts. Subjects taking intravenous AAT augmentation therapy are not required to wash out from IV AAT in the low and mid dose cohorts. At the high dose, two cohorts will be conducted in parallel to evaluate patients on and off IV augmentation therapy.
Phase 2 open label extension study to evaluate SAR447537 (INBRX-101) in adults with AATD emphysema
This is an open-label, 2-part, dose-escalating, Phase 1 study of INBRX-101 (rhAAT-Fc). Part 1 will consist of single ascending dose (SAD) administration of INBRX-101 and Part 2 will consist of multiple ascending dose (MAD) administrations of INBRX-101. The planned dosing schedule is IV every 3 to 4 weeks.
This is a Phase 2, multicenter, double-blind, randomized (1:1), placebo-controlled, 12-week, proof-of-concept study to evaluate the safety and tolerability as well as the mechanistic effect of oral administration of alvelestat (MPH966) in subjects with confirmed AATD defined as Pi\*ZZ, Pi\*SZ, Pi\*null, or another rare phenotype/genotype known to be associated with either low (serum AAT level \<11 μM or \<57.2 mg/dL) or functionally impaired AAT including "F" or "I" mutations.
The purpose of the study is to evaluate the safety and efficacy of administering repeated doses of Hyaluronic Acid Inhalation Solution to subjects with Emphysema that have Alpha-1-Antitrypsin deficiency
The objective of this study is to prospectively assess whether there is any interval between first symptom and initial diagnosis that is experienced by patients with newly diagnosed alpha-1 antitrypsin deficiency (AATD) and then to assess whether this diagnostic interval is associated with worsened clinical status at the time of initial diagnosis.
The aim of this study is to test whether aspirin improves endothelial function in alpha-1 antitrypsin deficiency-associated lung disease, measured by pulmonary microvascular blood flow on magnetic resonance imaging (MRI) and with apoptotic endothelial microparticles.
This is a 2-year open-label, multicenter extension of the double-blind, placebo-controlled GTi1201 study. The purpose of this study is to obtain an additional 2 years of safety data for intravenously administered Alpha1-MP 60 mg/kg/week in subjects with alpha1-antitrypsin deficiency (AATD).
The investigators hypothesize that there is liver injury (inflammation, fibrosis, cirrhosis) in adults with Alpha-1 Antitrypsin Deficiency (AATD), which is asymptomatic, under-recognized, and undiagnosed. In addition, the investigators believe that the genetic and environmental factors that play an important role in the development of alpha-1 antitrypsin (AAT) liver disease, can be identified by comparing a cohort database of clinical disease information to linked biospecimen and DNA samples.
This is a multi-center, randomized, placebo-controlled, double blind clinical study to assess the efficacy and safety of two separate dose regimens of Alpha-1 MP versus placebo for 156 weeks (i.e., 3 years) using computed tomography (CT) of the lungs as the main measure of efficacy. The two Alpha-1 MP doses to be tested are 60 mg/kg and 120 mg/kg administered weekly by IV infusion for 156 weeks. The study consists of an optional pre-screening phase, Screening Phase, a 156-week Treatment Phase, and an End of Study Visit at Week 160.
This project is designed to examine the interaction between the microflora in the lower airway and the concentration of a serum protein called alpha-1 antitrypsin. The hypothesis is that alpha-1 antitrypsin impacts the diversity and content of the lower airway microflora, resulting in a less inflammatory airway. The Specific Aims are: 1. To compare the lower respiratory tract microbiome and virome population diversity and content in age and GOLD stage matched PiZZ individuals not receiving augmentation therapy, PiZZ individuals on augmentation therapy, PiMZ individuals not receiving augmentation therapy, and PiMM individuals with chronic obstructive pulmonary disease (COPD). 2. Determine correlations between bronchoalveolar lavage (BAL) and peripheral blood gene expression patterns and patterns in lung microbial and viral populations across all cohorts. 3. Correlate the presence or absence of computed tomography (CT) bronchiectasis and bronchiolectasis with patterns in the microbiome population diversity and content. 4. To identify and define novel molecular phenotypes of Alpha-1 Antitrypsin Deficiency (AATD) based on computational integration of clinical, transcriptomic, and microbiome data.
We hypothesize that individuals with Alpha-1 Antitrypsin (AAT) deficiency have ongoing liver injury which is not detected by the usual blood tests used to look at liver function. This ongoing liver injury leads to cirrhosis in a significant number of adults with AAT deficiency.
Alpha-1 antitrypsin deficiency (AATD) is considered a rare genetic cause of chronic obstructive pulmonary disease (COPD) and liver disease. Recent data has suggested that AATD is not as rare as originally thought and undetected AATD may account for COPD in some patients. This study was designed to evaluate the frequency of undetected AATD in a population reporting to academic pulmonary function testing facilities who meet criteria for the diagnosis of COPD. All individuals meeting GOLD criteria for COPD will be consented and offered free testing for AATD. The results will help identify the percent of those with COPD who have undetected AATD.
The primary objective is to determine if the medication Carbamazepine, can be used as a therapy for patients with severe liver disease due to Alpha-1-Antitrypsin Deficiency .
This is a study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C (alpha1-proteinase inhibitor \[alpha1-PI\] \[Human\]), compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency (AATD).
Assessment of the safety and efficacy of intramuscular (IM) administration of a recombinant adenoassociated virus (rAAV) alpha-1 antitrypsin (AAT) vector (rAAV1-CB-hAAT) in AAT-deficient adults at three dosage levels \[6.0 × 10e11, 1.9 × 10e12 and 6.0 × 10e12 vector genome particles (vg) per kg body weight\]. Funding Sources - The FDA Office of Orphan Products Development and NIH National Heart, Lung, and Blood Institute
Individuals with a deficiency of alpha-1 antitrypsin (AAT) often develop emphysema. Traditional lung function tests may not be the most accurate way to measure the progression of emphysema. This study will compare high resolution computed tomography (CT) scans to spirometry to measure the progression of emphysema.
The primary purpose of this Phase II/III study is to demonstrate that Kamada-API, a new API concentrate manufactured by Kamada Ltd., is comparable to a currently marketed API product.
Individuals with a deficiency of the Alpha 1-antitrypsin (AAT) protein are at risk for developing emphysema and liver damage. Researchers have developed a way to introduce normal AAT genes into muscle cells so that the AAT protein is produced at normal levels. This study will evaluate the safety of the experimental gene transfer procedure in individuals with AAT deficiency.
The purpose of this randomized, double-blind, placebo-controlled study is to evaluate the short-term safety of inhaled recombinant alpha 1-antitrypsin (rAAT) in subjects with alpha 1-antitrypsin deficiency. The subjects are randomized to receive placebo or one of 4 doses of rAAT. The 4 doses are tested in a consecutive manner from lowest to highest.
The study was a Phase 1B/2A, uncontrolled, open-label, single-center study in individuals with congenital AAT (alpha 1-antitrypsin) deficiency. A baseline bronchoscopy with bronchoalveolar lavage (BAL) was performed 3 to a maximum of 4 weeks prior to the first administration of study drug. Fifteen eligible subjects were randomized to receive 1 of 3 dosing regimens of rAAT (100 mg daily, 100 mg twice daily, or 200 mg daily) administered via nebulization for 7 consecutive days. A post-treatment nadir BAL was obtained on study Day 8 (12 hours after last dose for subjects who receive drug therapy twice daily and 24 hours after the last dose for subjects who receive study product daily). BALs were conducted in the same lung lobe/segment. Follow-up visits took place on Day 15 and Day 36.
OBJECTIVES: I. Establish cell lines from patients with alpha 1-antitrypsin deficiency in order to examine genetic traits that predispose to liver injury.
Grifols Therapeutics Inc. conducted a multi-center, randomized, double-blind, crossover study to evaluate the safety, immunogenicity, and pharmacokinetics (PK) of Liquid Alpha₁-PI compared to the currently licensed product, Prolastin-C, in subjects with Alpha₁-Antitrypsin Deficiency (AATD).
This is a longitudinal, observational, non-interventional registry study, designed to collect both retrospective and prospective real world data, on patients receiving Alpha-1 augmentation therapy in the home through Coram Specialty Infusion.The data will be collected from standard Coram homecare forms, as well as patient reported case forms.
The goal of this clinical trial is to assess the safety and tolerability of a single oral dose of BMN 349 in participants with PiZZ or PiMZ/MASH. Primary outcome measures include incidence of any adverse events (including serious adverse events, dose limit toxicities, and adverse events of special interest), incidence of any laboratory test abnormalities, incidence of lung function test abnormalities and 12-lead ECG parameters. Participants will receive a single dose of either BMN 349 or placebo and then monitored for safety and tolerability.
Alpha-1 Anti-trypsin Deficiency (AATD) is a genetic disease with lung and liver disease presentations. Presentations are variable in the heterozygous population, the most predominant genotype being PiMZ. The purpose of this study in PiMZ heterozygous patients is to examine the density of the lung as measured by chest computed tomography (CT) and determine if existing emphysema predicts changes in the rate of subsequent emphysema or changes in CT, serum or plasma biomarkers of interest. The overarching goal is to develop biomarkers pertinent to the PiMZ patient that can be used in interventional trials since lung function changes do not typically inform disease progression in AATD.