Lakewood

Researchers are evaluating AV-380, an immunoglobulin G1 monoclonal antibody designed to bind human growth differentiation factor 15 GDF-15, a cytokine involved in cancer-induced cachexia. This phase 1B open-label dose escalation study aims to assess the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of AV-380 in cancer patients who have cachexia and elevated GDF-15 levels. Participants have metastatic solid tumors and are actively receiving standard of care chemotherapy. Participants receive AV-380 through intravenous infusion in ascending dose cohorts alongside their standard chemotherapy treatments. The study includes a dose escalation phase where the safety and appropriate dosage of AV-380 are evaluated. This phase allows researchers to monitor the effects of increasing doses of AV-380 over a study period of up to 4 months while patients continue their usual cancer therapies. During the study, participants will undergo assessments including monitoring for adverse events, toxicity, and laboratory abnormalities from enrollment until about 60 days after the last dose. Pharmacokinetic measures such as maximum concentration Cmax, time to maximum concentration Tmax, and area under the curve AUC will also be evaluated. The total involvement includes regular evaluations to track safety, drug behavior in the body, and immune responses to AV-380.

Researchers are evaluating the use of dexamethasone mouthwash as a preventive treatment for stomatitis related to Datopotamab Deruxtecan Dato-DXd in patients with metastatic or inoperable locally recurrent breast cancer or advanced or metastatic EGFR-mutated non-small cell lung cancer. This Phase IV, open-label, single-arm study aims to describe how often and how severe grade 2 or higher stomatitis occurs in participants receiving this prophylactic mouthwash during the first 12 weeks of Dato-DXd treatment. Participants will receive dexamethasone 0.5 mg5 mL alcohol-free mouthwash, swishing 10 mL four times daily for about 2 minutes and then spitting it out without swallowing. They must avoid food or drink for at least 30 minutes after use. This mouthwash will be used throughout their standard care treatment with Dato-DXd. The study includes two groups one with breast cancer and one with lung cancer patients, enrolling about 100 participants total over 18 months. During the study, participants will be monitored for stomatitis incidence and severity up to 12 weeks after starting treatment, with additional assessments up to about 21 months for onset and resolution timing. Researchers will also track adherence to the mouthwash, any dose changes in Dato-DXd due to stomatitis, and overall safety. Follow-up for safety continues for 28 days after the last study dose, with various evaluations including clinical assessments throughout the treatment period.

Researchers are conducting a 10-year observational study called the Congenital Muscle Disease Patient and Proxy Reported Outcome Study CMDPROS. This study aims to collect and analyze care data and adverse events for various congenital muscle diseases using the Congenital Muscle Disease International Registry CMDIR. The study focuses on individuals with diagnoses such as congenital muscular dystrophy, congenital myopathy, congenital myasthenic syndrome, and related conditions, including those without genetic confirmation. Understanding these conditions better will help improve care standards and support future clinical trials. Participants register in the CMDIR by providing demographic information and completing an intake survey. They are also asked to share medical records related to their diagnosis and treatment, such as genetic testing results, muscle biopsy reports, pulmonary function tests, sleep studies, clinic notes, and hospital discharge summaries. The study collects data on multiple disease subtypes and tracks various health events and care parameters over time, aiming to build a comprehensive database. Throughout the study, participants provide ongoing information about their health status and adverse events, which researchers verify using medical records. Key outcomes include survival rates, hospitalization frequency, respiratory complications, and other health complaints. The study will also analyze measures like ejection fraction, lung function, sleep study results, growth, fractures, and bone density. Data collected will contribute to evidence-based care guidelines and help identify meaningful outcomes for future clinical trials. Participation requires no travel as data collection is done remotely through the registry.

This research aims to identify hidden small airways obstruction in children and adults with cystic fibrosis who have normal results on routine pre-bronchodilator lung function tests. It focuses on patients with both heterozygous and homozygous cystic fibrosis and explores the presence of lung issues not detected by usual spirometry measures like FEV1, FVC, and their ratios. The study builds on previous findings that small airways obstruction and emphysema can exist despite normal routine lung function tests. Participants undergo diagnostic tests including spirometry and lung CT scans to detect abnormal expiratory airflow at low lung volumes, which may indicate small airways obstruction or peripheral airway bronchiectasis. The study is retrospective and observational, assessing maximal expiratory flow volume loops at 75% and 80% expired lung volume to find airway limitations that routine tests might miss. During the study, researchers analyze existing lung function data and imaging results to measure small airway obstruction in cystic fibrosis patients. The main outcome is the detection of unsuspected small airway obstruction over a 5-year period. Participants routine spirometry results are reviewed alongside specialized measurements to better understand lung function in this population, helping to inform future diagnosis and management strategies.

Researchers are studying chronic, stable asthmatics who do not smoke, focusing on understanding what causes expiratory airflow limitation in moderate to severe persistent asthma. This research aims to identify whether the large or small airways mainly contribute to airflow problems and to explore the role of small airway obstruction and loss of lung elastic recoil. The study also evaluates how different doses of inhaled corticosteroids affect inflammation in these airways, using exhaled nitric oxide as a marker. Measurements will also be taken during naturally occurring asthma exacerbations for comparison. Participants receive treatment with inhaled corticosteroids and long-acting beta2-agonists such as fluticasonesalmeterol or budesonideformoterol in varying doses. This is an observational study where additional treatments might include antibiotics and tapering corticosteroids. Researchers will also perform lung function studies, imaging including high-resolution CT scans, and fiberoptic bronchoscopy with optical coherence tomography to assess lung structure and function. During the study, participants will undergo regular assessments including spirometry, measurements of exhaled nitric oxide, and lung function tests over periods ranging from 20 to 60 days and up to 5 years. Data from lung autopsies of asthmatics will be compared when available. The study monitors mechanisms of airflow limitation and presence of emphysema, aiming to better understand the disease process. Participants are observed without masking or randomization, and the total follow-up can extend from months to years.

This research aims to understand the causes and sites of expiratory airflow limitation in people with moderate to severe persistent asthma who are stable, treated, and non-smokers. The study focuses on whether airflow limitation mainly occurs in large or small airways and how much is due to airway obstruction or loss of lung elastic recoil. Researchers will use markers like exhaled nitric oxide to assess airway inflammation and will also study lung changes during asthma flare-ups and stable periods, including detailed imaging and tissue analysis when available. Participants will receive treatment with one of three inhaled corticosteroid and long-acting beta2-agonist combinations fluticasonesalmeterol, budesonideformoterol, or mometasoneformoterol, combined with tiotropium daily. For acute flare-ups, albuterol and ipratropium will be used as needed. The study includes measurements of lung function and quality of life questionnaires. Imaging such as high-resolution CT scans and optical coherence tomography will be performed to evaluate lung structure and detect emphysema. During the study, participants will undergo tests including spirometry with special gas mixtures to locate airflow limitation and exhaled nitric oxide measurements to monitor inflammation over 20 to 60 days. Researchers will also analyze lung tissue from autopsies or transplants when available. The main outcomes include assessing airway inflammation, airflow limitation sites, lung elastic recoil loss, and the presence and extent of emphysema. The study runs until June 2027, with detailed evaluations during stable periods and exacerbations.

This research aims to evaluate the effects of combining baxdrostat with dapagliflozin compared to dapagliflozin alone in adults aged 40 and older who have type 2 diabetes, established cardiovascular disease, a history of hypertension with a systolic blood pressure of at least 130 mmHg, and at least one additional risk factor for heart failure. The study is a phase III, randomized, placebo-controlled trial focusing on preventing heart failure events and cardiovascular death. Participants will be randomly assigned to receive either baxdrostat with dapagliflozin or placebo with dapagliflozin. Those starting the baxdrostatdapagliflozin treatment may begin with a lower baxdrostat dose that can be increased if certain criteria are met. A run-in period with dapagliflozin alone for 4 to 6 weeks may occur for those not previously treated or treated less than 4 weeks with SGLT2 inhibitors. Treatment visits will occur at about 2, 4, 8, 16, and 34 weeks after randomization, then every 4 months until study closure. Participants will undergo screening for eligibility within a 14-day period, with an optional pre-screening phase that does not require site visits or consent. During the study, regular assessments including monitoring for heart failure events and cardiovascular outcomes will be conducted. If participants stop the blinded treatment early, they may continue with open-label dapagliflozin unless specific discontinuation criteria apply. The study will continue until a predetermined number of cardiovascular events occur, with ongoing data collection and visits according to protocol.

Researchers are investigating the site and mechanisms responsible for expiratory airflow limitation in people who have chronic obstructive pulmonary disease COPD, emphysema, or asthma-COPD overlap. The study focuses on current or former smokers with a history of more than 15 pack years who have mild to severe expiratory airflow limitation. It aims to understand whether airflow limitation is due to problems in large central airways, small peripheral airways, loss of lung elastic recoil, or a combination of these factors. Participants will undergo extensive lung function tests including spirometry before and after inhaled bronchodilation, lung volume measurements, diffusing capacity, and lung elasticity assessment involving an esophageal balloon. Imaging studies include high-resolution CT scans of the lungs to measure emphysema and bronchiectasis. Blood tests and possibly bronchoscopy may also be performed to gather additional information. The study groups are categorized based on clinical, pathologic, laboratory, physiological, and radiological differences. During the study, participants will have assessments including lung function tests, blood tests, exhaled nitric oxide measurement, and imaging scans. Some tests may be uncomfortable but are expected to cause no harm. The primary measurement is to identify the site and mechanisms of expiratory airflow limitation over a four-year period. The study started in 2017 and is planned to continue through 2027, with participant involvement varying depending on the tests performed.

Researchers are evaluating BMS-986368, a FAAHMAGL inhibitor, for treating agitation in people with Alzheimers Disease. This Phase 2 study aims to assess the drugs effectiveness, safety, and tolerability in this population. Participants must have confirmed Alzheimers disease with biomarkers and meet specific agitation criteria based on established clinical definitions. Participants will be randomly assigned to receive one of two doses of BMS-986368 or a placebo. The study is double-blind and will take place across multiple centers. The treatment is given orally on specified days, and the study includes a placebo control for comparison. The trial is designed to last up to 8 weeks for primary assessments, with additional monitoring for safety and drug levels extending up to 14 weeks. Participants will undergo various assessments including the Cohen-Mansfield Agitation Inventory CMAI to measure agitation changes, Clinical Global Impression-Severity CGI-S, and Neuropsychiatric Inventory Nursing Home Version NPI-NH scores. Safety evaluations include monitoring adverse events and laboratory tests. The study also tracks potential withdrawal symptoms and drug plasma concentrations. Total participation may last up to 14 weeks, including follow-up after the last dose.