Jefferson

Researchers are evaluating the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adults diagnosed with moderate-to-severe Major Depressive Disorder (MDD). This Phase 3, multicenter, randomized, double-blind, placebo-controlled study focuses on participants aged 18 to 74 who have experienced their first major depressive episode before age 50. The study aims to compare azetukalner with placebo in treating MDD over a 6-week period. Participants will receive either azetukalner 20 mg or placebo orally once a day with food, preferably with the evening meal, for 6 weeks. The treatment is administered as a daily oral dose, and participants are randomly assigned to one of the two groups. The study is designed to maintain blinding of treatments to both participants and researchers. During the study, participants' depression symptoms will be assessed using the Hamilton Depression Rating Scale (HAMD-17) to measure changes from baseline to Week 6. Researchers will also monitor safety and tolerability throughout the treatment period. Participants will undergo regular evaluations, and the study includes careful screening to ensure eligibility and monitor any adverse effects during the 6 weeks of treatment.

Researchers are evaluating ASP5834 in adults with certain KRAS gene mutations who have locally advanced, unresectable, or metastatic solid tumors, including colorectal cancer, non-small-cell lung cancer, and pancreatic ductal adenocarcinoma. This Phase 1 study aims to find a suitable dose and assess the safety and tolerability of ASP5834 alone or combined with panitumumab, a treatment for colorectal cancer. The study focuses on people who have not responded to or are ineligible for standard treatments. It is an open-label trial, so participants and staff know the treatments being given. The study has two parts: Dose Escalation and Dose Expansion. In Dose Escalation, small groups receive increasing doses of ASP5834 alone or with panitumumab (for colorectal cancer patients only) via intravenous infusion. In Dose Expansion, other groups receive the most suitable doses identified earlier. Treatment cycles last 21 or 28 days, with participants continuing until they experience intolerable side effects, cancer progression, start other treatments, or choose to stop. Participants will visit the clinic regularly during treatment, especially in the first two cycles, for health checks, scans, tumor biopsies, and monitoring for side effects. After stopping treatment, they will have follow-up visits every few months to monitor their cancer and health. The study is expected to last about one year per participant. Researchers will measure safety outcomes including adverse events, laboratory abnormalities, heart and eye exams, and physical condition assessments throughout the study.

Researchers are evaluating the safety, tolerability, and early effectiveness of ziftomenib, an investigational oral drug, combined with standard treatments for patients with acute myeloid leukemia (AML) who have specific genetic changes such as NPM1 mutation or KMT2A rearrangement. This study includes both newly diagnosed and relapsed or refractory AML patients and aims to understand the benefits and risks of adding ziftomenib to current therapies. The trial is a Phase 1 study focusing on patients with these genetic alterations and different AML statuses. The study involves three separate treatment groups where ziftomenib is combined with standard-of-care drugs including venetoclax (oral), azacitidine (subcutaneous or intravenous), standard chemotherapy drugs daunorubicin and cytarabine (both intravenous), and quizartinib (oral). Depending on the cohort and physician decision, patients receive one of these combinations, with specific dosing schedules and administration routes. Some patients may receive intensive chemotherapy regimens with these drugs, and contraception requirements apply for participants of childbearing potential. Participants will be closely monitored for side effects such as dose-limiting toxicities during the first 28 days of treatment, with ongoing assessment of adverse events up to 28 days after 36 months of treatment. The trial will measure the rate of complete remission and track relapse, new therapies, or death over up to 36 months. Safety tests, including heart monitoring with ECGs, laboratory tests, and physical assessments, will be performed regularly to ensure participant safety throughout the study and follow-up periods.

Researchers are investigating a treatment approach for patients hospitalized with community-acquired pneumonia (CAP), a condition with high rates of illness and death. This phase 3 trial compares therapeutic-dose heparin versus usual care pharmacological thromboprophylaxis to see if it improves patient outcomes. The study focuses on preventing complications caused by blood clots and inflammation that can worsen respiratory and organ function in CAP patients. Previous findings in COVID-19 pneumonia suggest heparin might reduce disease progression and mortality, but its effects in non-COVID-19 CAP are unknown. Participants will receive either therapeutic-dose heparin, preferably a low molecular weight heparin (LMWH) like enoxaparin, dalteparin, or tinzaparin, dosed by patient weight unless contraindicated. Intravenous unfractionated heparin (UFH) may be used instead, especially for those with kidney issues, with dosing adjusted to specific blood clotting targets. The trial is open-label and randomized, with adaptive rules to monitor progress. Usual care pharmacological thromboprophylaxis is the comparator. Treatment and monitoring occur during hospital admission, anticipated to last at least 72 hours after randomization. During the study, patients are assessed for survival at 30 days and monitored for complications related to CAP. Researchers collect clinical data including oxygen use, laboratory tests, and adverse events, tracking safety and effectiveness. The study excludes patients with active COVID-19, recent bleeding, contraindications to anticoagulation, or those receiving critical care interventions. Overall participation depends on hospital stay length and clinical status, with follow-up to evaluate the primary outcome of survival within a month.

This research aims to enhance care and improve outcomes for infants diagnosed with Hypoplastic Left Heart Syndrome (HLHS). It focuses on expanding the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) national registry to collect detailed clinical care process, outcome, and developmental data on infants from diagnosis until 12 months of age. The initiative also seeks to promote the use of consensus care standards across pediatric cardiology centers while actively involving parents as partners in the care process. The study evaluates a Collaborative Learning Network intervention designed to support the implementation of care improvements. Pediatric cardiology centers participate by applying tested consensus standards into routine practice to ensure consistent and improved care delivery for infants with HLHS. The initiative includes data collection on care processes and outcomes, aiming to foster collaboration and learning among clinical teams. Participants are infants diagnosed with HLHS or related univentricular heart conditions who are intended to undergo the Norwood procedure. Researchers track changes in care delivery over a 15-month period through the expanded registry, monitoring clinical and developmental outcomes. Parent engagement is encouraged to support care improvements. The study does not specify exclusion criteria, allowing broad participation of eligible infants within the first 12 months of life.

Researchers are evaluating the safety and early antitumor effects of Pocenbrodib, alone or combined with Abiraterone acetate, Olaparib, or 177Lu-PSMA-617, in men with metastatic castration-resistant prostate cancer (mCRPC) who have progressed despite prior anti-androgen therapy. This Phase 1b/2a open-label study aims to find the appropriate dose and assess pharmacokinetics, pharmacodynamics, and preliminary efficacy of these treatments. The study begins with a Phase 1b dose-escalation portion where participants receive increasing doses of Pocenbrodib alone on a 5 days on/2 days off schedule. After confirming safety and a minimum threshold of efficacy, Phase 2a enrolls participants into four cohorts: Pocenbrodib monotherapy and three combination therapy groups with Abiraterone acetate, Olaparib, or 177Lu-PSMA-617. Each cohort is studied independently for safety and effectiveness. Participants undergo imaging and laboratory tests to confirm disease status and monitor treatment effects. Researchers measure dose-limiting toxicities and recommended Phase 2 dose over 28 days, as well as objective tumor response and prostate-specific antigen (PSA) levels up to an estimated six months. Safety and treatment responses are closely followed throughout the study duration.

Pancreatic ductal adenocarcinoma (PDAC) is a highly deadly cancer often detected only at advanced stages, making treatment difficult. Early detection is rare, and current blood markers like serum carbohydrate antigen 19-9 (CA19-9) are unreliable for identifying early disease. Researchers aim to validate a new method using exosome-based microRNA (miRNA) signatures for noninvasive, early detection of pancreatic cancer in a large international study. The study evaluates the PANcreatic cancer Exosome Early detectiON (PANXEON) test, which measures levels of 5 cell-free and 8 exosome-contained miRNAs in plasma using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). This diagnostic test will be applied to plasma samples from patients with pancreatic ductal adenocarcinoma and individuals without the disease to assess its ability to detect early-stage cancer. Participants will undergo blood sample collection for miRNA analysis. Researchers will monitor the sensitivity of the test over about one year to determine how accurately it detects pancreatic cancer. The study will compare miRNA levels in patients with PDAC to those in non-disease controls to confirm the test's effectiveness in early cancer identification.

The Pulmonary Hypertension Association Registry (PHAR) is a nationwide study focused on people living with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). It collects detailed information from patients treated at PHA-accredited Pulmonary Hypertension Care Centers across the United States. The study aims to understand how patients with these conditions are evaluated, tested, and treated, and to observe their health outcomes over time. Participants include people of all ages diagnosed with PAH, CTEPH, or pediatric pulmonary hypertension caused by developmental lung disease, who are within six months of their first outpatient visit at a PH Care Center. The study gathers comprehensive data on diagnosis, clinical and socioeconomic status, test results, body measurements, treatments, interest in clinical trials, family and social history, and lifestyle factors such as smoking and alcohol use. Participants provide updates on therapy changes, hospital visits, and survival, helping researchers track disease progression and treatment adherence. Researchers monitor participants for up to 10 years to assess how many complete all recommended diagnostic tests, the impact of clinical factors on disease worsening, and overall survival. The information collected may help improve care and outcomes for people with pulmonary hypertension by identifying best practices and risk factors.

Researchers are evaluating the effect of Seladelpar on clinical outcomes in patients with Primary Biliary Cholangitis (PBC) who have compensated cirrhosis. This Phase 3 study focuses on adults with PBC and cirrhosis classified as Child-Pugh (CP) score A or B to better understand how Seladelpar may impact the disease course compared to placebo treatment. Participants will be assigned to receive either Seladelpar or a placebo daily for up to 36 months. Those with CP-A cirrhosis will take 10 mg of Seladelpar once daily, while those with CP-B cirrhosis will take 5 mg once daily. The placebo group will take one capsule daily for the same duration. This randomized, double-blind, placebo-controlled design ensures that the effects of Seladelpar can be assessed rigorously against a control. Throughout the study, participants will be monitored regularly with scheduled assessments to evaluate their health and response to treatment. Researchers will measure Event Free Survival over 36 months as the primary outcome. Safety and liver function will be closely observed through laboratory tests and clinical evaluations. Participants must comply with study requirements and complete all scheduled visits during the treatment period.

Researchers are evaluating the progression-free survival (PFS) of casdatifan compared to placebo, each given with cabozantinib, in adults with advanced or metastatic clear cell Renal Cell Carcinoma who have experienced disease progression after prior anti-PD-1 or anti-PD-L1 immunotherapy. This is a Phase 3, randomized, double-blind, active-control trial focusing on this patient population. Participants receive treatment with either casdatifan plus cabozantinib or placebo plus cabozantinib as specified in the treatment arms. The study compares these combinations to assess their effects on the cancer. Treatment is administered according to the assigned group throughout the study period. During the study, patients undergo regular evaluations including imaging to measure tumor response by RECIST 1.1 criteria. Progression-free survival is assessed by a central independent review over approximately 33 months. Additional assessments include monitoring of organ and marrow function and safety evaluations. Participants may be followed for long-term safety and efficacy outcomes.