Lakewood

Researchers are conducting a Phase 1B open-label dose escalation study to evaluate AV-380 in cancer patients experiencing cachexia, a condition involving severe weight loss and muscle wasting. AV-380 is a monoclonal antibody designed to bind to the growth differentiation factor 15 (GDF-15), a protein involved in cancer-related cachexia. The study aims to assess the safety, how the drug moves through and affects the body (pharmacokinetics and pharmacodynamics), and its potential immune response effects in patients actively receiving standard cancer treatments. Participants will receive increasing doses of AV-380 alongside their standard of care chemotherapy to determine appropriate dosing and monitor for any adverse effects. AV-380, a biological therapy, targets GDF-15 to potentially impact cachexia symptoms. The study involves treatment periods lasting up to four months, with careful observation during drug administration and follow-up visits. Throughout the study, participants will be closely monitored for adverse events, toxicity, and laboratory abnormalities from the time of enrollment through approximately 60 days after the last dose. Safety assessments and laboratory tests will be regularly conducted to evaluate the body's response to AV-380. The study involves active cancer patients with cachexia, with various evaluations to understand the drug's safety profile and effects over the study duration.

Researchers are conducting a 10-year observational study called the Congenital Muscle Disease Patient and Proxy Reported Outcome Study (CMDPROS) to track care practices and adverse events in people with congenital muscle diseases. This study uses data from the Congenital Muscle Disease International Registry (CMDIR), which includes individuals diagnosed with various congenital muscular dystrophies, myopathies, and myasthenic syndromes. The goal is to build a detailed database that helps understand disease progression, care outcomes, and adverse events across different subtypes of these rare genetic conditions. Participants register in the CMDIR by providing demographic details and completing an intake survey. They are then asked to share medical records related to their diagnosis and treatment, including genetic testing, muscle biopsies, pulmonary tests, sleep studies, clinic notes, and hospital discharge summaries. The study collects data from affected individuals globally without requiring travel. It also includes preliminary studies focusing on specific subtypes using retrospective and prospective data collection methods. Throughout the study, researchers will monitor survival rates, adverse events such as hospitalizations and infections, and various health measures like pulmonary function, weight, sleep quality, and bone density. Patient and proxy reports will be confirmed with medical documentation to ensure accuracy. The data will support future research, help establish care guidelines, and contribute to clinical trials aimed at improving treatment and quality of life for people with congenital muscle diseases.

Researchers are studying children and adults with treated heterozygous and homozygous cystic fibrosis who show normal results on routine lung function tests. The study aims to detect hidden small airways obstruction that routine pre-bronchodilator spirometry tests may miss. This retrospective study builds on previous research showing small airway problems and emphysema can exist even when common lung function measures appear normal. The study involves measuring lung function using spirometry and lung CT scans to analyze maximal expiratory flow volume loops at low lung volumes. This method can reveal isolated abnormal airflow limitations at 75% and 80% of expired lung volume, indicating small airway obstruction and peripheral airway bronchiectasis despite normal routine spirometry. Participants will have their lung function and CT images reviewed to detect these subtle abnormalities. Researchers will assess maximal expiratory flow volume loops and low lung volume airflow to identify unsuspected airway issues. The study will measure the detection of small airway obstruction over a 5-year period, focusing on patients with cystic fibrosis who have normal routine lung function tests.

Researchers are investigating the causes and locations of expiratory airflow limitation in people with chronic, stable asthma who do not smoke. This study focuses on adults and adolescents with moderate to severe persistent airflow obstruction despite treatment with inhaled corticosteroids and long-acting beta2 agonists. The goal is to determine whether airflow limitation mainly occurs in the large or small airways, and whether small airway obstruction or loss of lung elastic recoil plays a role. The study also examines the effects of different inhaled corticosteroid doses on airway inflammation using exhaled nitric oxide as a marker. Assessments will also be made during natural asthma exacerbations for comparison.

Researchers are investigating the causes and location of airflow limitation in people with moderate to severe persistent asthma who are stable, treated, and non-smokers. The study aims to understand whether the large or small airways are mainly affected and whether airflow limitation is due to airway obstruction or loss of lung elastic recoil. The research also evaluates the effects of different doses of inhaled corticosteroids on airway inflammation using exhaled nitric oxide as a marker. Additional tests during asthma flare-ups will help compare inflammation and lung function changes. Advanced imaging, including high-resolution CT and optical coherence tomography, will assess lung tissue and emphysema presence, and autopsy samples may be studied if available. Blood tests will measure serum periostin as another inflammation marker in collaboration with Genentech. Participants will receive treatments such as budesonide/formoterol, fluticasone/salmeterol, mometasone/formoterol, or prednisone as needed. The inhaled medications are given in various doses and schedules, including twice daily inhalations and once daily doses, with no placebo group. The study measures lung function and inflammation markers before and after treatment, and during exacerbations when possible. Participants will undergo tests like spirometry, exhaled nitric oxide measurement, and high-resolution lung scans. Researchers will analyze airflow limitation using specialized breathing tests with gas mixtures to identify affected airway regions. The study also looks at lung structure integrity and emphysema extent. Some participants may provide samples after death or lung transplant for further examination. The main outcomes focus on airflow limitation mechanisms, inflammation levels, and lung tissue health over the study period, which ranges from 10 days post-mortem to 20-60 days for other measures.

The trial investigates the long-term safety and tolerability of KarXT in people with psychosis associated with Alzheimer's Disease. This Phase 3 global, multicenter, open-label extension study lasts 52 weeks and enrolls participants who have completed earlier related studies (CN012-0026, CN012-0027, or CN012-0056). The purpose is to monitor how well patients tolerate KarXT over an extended period and to collect safety data. Participants receive KarXT in varying doses taken three times daily, ranging from 20/2 mg up to 66.7/6.67 mg per dose, corresponding to total daily doses between 60/6 mg and 200/20 mg. This treatment is provided throughout the 52-week open-label extension. The study includes only those who completed the previous related studies and continues to assess their response to KarXT over this longer timeframe. During the study, participants are closely monitored for treatment-emergent adverse events from the first dose through 14 days after the final dose, which may be up to 54 weeks. Regular assessments ensure safety and tolerability, and caregivers are involved to support participants. The study also evaluates participants' ability to continue living in their current setting and requires consent from the participant or their legal representative. Overall, the study tracks long-term safety outcomes in this specific patient group.

Researchers are evaluating the effects of baxdrostat combined 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 systolic blood pressure of at least 130 mmHg at screening, and at least one additional risk factor for heart failure. This Phase III randomized, placebo-controlled, event-driven study aims to determine if the combination reduces the risk of heart failure events or cardiovascular death, with follow-up lasting up to 38 months. Participants who meet screening criteria but are not currently treated with SGLT2 inhibitors or have been treated for less than 4 weeks will enter a run-in period receiving dapagliflozin 10 mg once daily for 4 to 6 weeks before randomization. The study involves random assignment to either baxdrostat plus dapagliflozin or placebo plus dapagliflozin. Site visits occur at approximately 2, 4, 8, 16, and 34 weeks after randomization, then every 4 months. Participants discontinuing the blinded study drug may continue open-label dapagliflozin, with ongoing visits and data collection as per protocol. Participants will undergo an optional pre-screening period without site visits or consent to help identify eligibility, followed by up to 14 days of formal screening after informed consent. Researchers will monitor heart failure events and cardiovascular deaths as primary outcomes. Safety and adherence will be tracked throughout the study, including during any premature discontinuation of blinded treatment. The study will conclude when a predetermined number of secondary endpoint events have occurred, with continued follow-up as needed.

Researchers are evaluating the safety and effectiveness of up to two injections of REACT/rilparencel in adults with type 2 diabetes mellitus and chronic kidney disease. This phase 3 randomized controlled study divides participants into two groups to compare the effects of the actual treatment versus sham procedures mimicking kidney biopsy and injections. The goal is to monitor kidney function and clinical outcomes over time to understand the impact of this therapy on disease progression. Participants are randomly assigned before a kidney biopsy to either receive sham procedures or the real treatment involving a kidney biopsy followed by two rilparencel injections about 12 weeks apart, each into different kidneys. Those receiving sham procedures will undergo similar-sounding and looking activities without actual tissue removal or injection. All participants will be followed until the study's global end date, ensuring consistent long-term observation. During the study, participants will undergo kidney biopsies or sham procedures, followed by injections or sham injections. Researchers will assess kidney function by measuring the slope of estimated glomerular filtration rate (eGFR) over 18 months after the 135th participant's first injection or sham procedure. They will also track clinical events such as significant kidney function decline, need for dialysis or transplant, or renal and cardiovascular deaths for up to 94 months. Safety and efficacy will be monitored throughout the study to evaluate treatment impact.

Researchers are studying the site and reasons for expiratory airflow limitation in people with COPD, Emphysema, and Asthma-COPD Overlap who are current or former smokers with a history of more than 15 pack years. The study focuses on those with mild to severe airflow limitation and evaluates whether airflow issues come from large central airways or small peripheral airways and alveoli. The goal is to understand how lung function is affected, including the role of lung elastic recoil and obstruction, by using detailed lung imaging and tests. Some participants may have had asthma before developing COPD, and treatments they may be using include inhaled bronchodilators, corticosteroids, antibiotics, supplemental oxygen, and other medications. Participants undergo a variety of lung function tests such as spirometry before and after inhaled bronchodilators, lung volume measurements, diffusing capacity, lung elasticity tests involving an esophageal balloon, airflow assessments after breathing a helium-oxygen mixture, and exhaled nitric oxide measurements. High-resolution CT scans assess emphysema extent and distribution, and in some cases, bronchoscopy may be performed. Blood tests include complete blood count, serum IgE, metabolic panel, and alpha-1 antitrypsin levels. Lung tissue from surgical or autopsy samples may also be studied when available. During the study, participants will be carefully evaluated with these tests to measure airflow limitation sites and mechanisms. Researchers will monitor lung function and imaging findings over four years to understand airflow problems better. The tests may cause some discomfort but are not expected to cause harm. This study helps clarify lung changes in chronic lung diseases among smokers to improve knowledge about airway obstruction.

Researchers are evaluating the safety, tolerability, and effectiveness of BMS-986368, a FAAH/MAGL inhibitor, in treating agitation in people diagnosed with Alzheimer's disease. This Phase 2 study focuses on participants who meet the 2024 revised criteria for Alzheimer's diagnosis and staging, along with confirmed agitation as defined by the International Psychogeriatric Association. The study aims to better understand how this medication may impact agitation symptoms in this population. Participants will be randomly assigned to receive either BMS-986368 or a placebo, both administered orally at specified doses on certain days. The study is designed as a double-blind, three-arm, placebo-controlled trial conducted across multiple centers. Treatment effects will be assessed up to 8 weeks, with participants monitored closely throughout the treatment period. During the study, participants will be regularly assessed for changes in agitation using the Cohen-Mansfield Agitation Inventory (CMAI) total score from baseline through week 8. Researchers will also monitor safety and tolerability throughout the trial. Participants must have a stable living environment and a study partner or caregiver to support their involvement. The total duration includes screening and treatment periods, with ongoing evaluations to measure treatment impact and safety.