Durham

Researchers are evaluating the safety and effectiveness of elenestinib (BLU-263) combined with symptom-directed therapy (SDT) compared to placebo plus SDT in people with indolent systemic mastocytosis (ISM) whose symptoms are not well controlled by SDT alone. This Phase 2/3 randomized, double-blind, placebo-controlled study includes participants with ISM and smoldering systemic mastocytosis, and also involves groups for pharmacokinetic studies and participants who previously received a selective KIT inhibitor. The study is divided into multiple parts. Parts 1 and 2 enroll participants with ISM who will receive either elenestinib oral tablets or placebo alongside their symptom-directed therapy. Participants from Part 2 may continue into Part 3, which is an open-label extension where all receive elenestinib. Part K enrolls participants with ISM who have prior experience with selective KIT inhibitors. The study tracks treatment effects and safety over time. Participants will be monitored for up to 5 years, with assessments including the number of treatment-emergent adverse events, changes in symptom scores measured by the ISM-Symptom in Assessment Form, and overall safety monitoring. Evaluations occur at baseline, 13 weeks, 49 weeks, and throughout the long-term follow-up. The study also includes detailed tracking of symptom control and adverse events to evaluate the impact of treatment on participants' health and quality of life.

This research aims to assess the ability of 129Xe MRI/MRS biomarker signatures to non-invasively monitor pulmonary vascular reverse remodeling in patients with pulmonary arterial hypertension (PAH) treated with sotatercept. The study is conducted in Phase 2 and focuses on predicting short- and long-term treatment response and efficacy using advanced imaging techniques alongside standard clinical assessments. PAH involves obstructive changes in the lung blood vessels leading to heart failure, and current treatments mainly work by dilating vessels without reversing remodeling, highlighting the need for therapies like sotatercept that target this remodeling directly. Participants will undergo 129Xe MRI/MRS scans at baseline before starting sotatercept treatment, then again at 3 and 12 months. These scans will measure ventilation defects, red blood cell defects, membrane uptake, and oscillation amplitudes as markers of lung function and vascular remodeling. Sotatercept will be administered as part of the clinical standard-of-care, with xenon gas doses limited to less than 25% of lung capacity to ensure safety during imaging. Throughout the study, participants will have multiple assessments including laboratory tests, echocardiography, NTproBNP blood marker measurements, and a 6-minute walk distance test at each visit. Researchers will track changes in imaging biomarkers and clinical outcomes such as hospitalizations and mortality to evaluate sotatercept's impact on pulmonary vascular remodeling. The total follow-up period per participant will be 12 months, allowing detailed monitoring of treatment effects and lung function over time.

Researchers are evaluating the use of 129 Xenon MRI as a biomarker for diagnosing and monitoring Pulmonary Arterial Hypertension (PAH), including common subtypes such as Idiopathic PAH and PAH associated with connective tissue disease (PAH-CTD). This Phase 2 observational study aims to identify specific MRI signatures that can differentiate these subtypes and to assess how well the MRI tracks disease progression and response to treatment over time. Additional assessments like laboratory tests, echocardiography, and six-minute walk distance (6MWD) are included to support the evaluation.

Researchers are studying three biomarkers from 129Xe gas exchange MRI to understand how they change after different treatments. These biomarkers focus on the interaction of 129Xe with red blood cells in the lungs, including RBC transfer MRI, heart-related oscillations in the 129Xe-RBC signal, and changes in the 129Xe-RBC chemical shift. The study includes healthy volunteers and patients with conditions such as interstitial lung disease, idiopathic pulmonary fibrosis, non-specific interstitial pneumonias, chronic hypersensitivity pneumonitis, sarcoidosis, chronic thromboembolic pulmonary hypertension, acute pulmonary embolism, anemia, polycythemia, and shortness of breath. Participants receive hyperpolarized xenon gas in doses up to 25% of their total lung capacity, followed by a breath hold of up to 15 seconds. Some patients will also receive oxygen therapy. Groups include healthy volunteers, patients scheduled for red blood cell transfusion or therapeutic phlebotomy, and those with lung or heart-related conditions. Patients with chronic thromboembolic pulmonary hypertension may have surgery and return 3 to 6 months later for follow-up scans. During the study, participants undergo MRI scans before and after treatments such as transfusion, apheresis, or oxygen administration. Researchers measure changes in red blood cell to membrane ratio, chemical shift after oxygen, and oscillation amplitude over time. The study monitors safety and participants' ability to hold their breath during imaging. The time frame includes assessments up to 5 days before and after transfusion or apheresis and follow-ups 3 to 6 months post-treatment.

Researchers are evaluating a new imaging technology called 4D Microscope Integrated Optical Coherence Tomography (4D MIOCT) combined with a Zeiss Artevo 800 surgical microscope. The study focuses on adults undergoing eye surgery for corneal, retinal, or other ocular diseases. The goal is to assess how easy and safe the 4D MIOCT system is to use during various anterior and posterior segment eye surgeries and to visualize the eye's structures effectively. The 4D MIOCT device is integrated into the Zeiss Artevo 800 surgical microscope and includes an investigational 3D OCT scanner. This imaging system will be used during the participants' clinically-indicated eye surgeries without any additional treatment or surgical intervention for research purposes. The study is observational, capturing images during standard ophthalmic microsurgery and comparing them to other clinical images obtained as part of usual care. Participants will have their eye images recorded during surgery using the 4D MIOCT device. Researchers will also review medical records from up to three previous eye care visits to gather clinical data, including ocular health and prior treatments. The images and data will be analyzed after surgery to evaluate the device's performance and explore whether it provides new information beyond existing clinical imaging. There is no extra risk to participants beyond their scheduled surgery.

This research aims to evaluate the effects of litifilimab (BIIB059), a monoclonal antibody, in adults with active subacute or chronic cutaneous lupus erythematosus (CLE), with or without systemic lupus erythematosus (SLE). Participants have active skin symptoms of CLE that have not improved with antimalarial therapy or had difficulties continuing that treatment. The study focuses on reducing skin disease activity using several scores including CLA-IGA-R and CLASI, while also assessing safety, immune response, and quality of life. Participants will be randomly assigned to receive either litifilimab or a placebo injection under the skin every four weeks during a 24-week double-blind period where neither participants nor researchers know which treatment is given. After this, all participants will receive litifilimab injections every four weeks for an additional 28 weeks. Those who complete the treatment may join a long-term extension study or enter a follow-up safety period lasting up to 24 weeks. Total participation may last up to 80 weeks. Throughout the study, researchers will monitor skin disease activity using the CLA-IGA-R erythema score and the CLASI-A activity score to see how many participants improve. They will also assess safety, tolerability, immune system effects, and participants' quality of life using questionnaires. These evaluations occur regularly during both treatment periods and follow-up to understand the impact of litifilimab on CLE symptoms and overall health.

Researchers are evaluating KTX-2001, alone and combined with darolutamide, in men with metastatic castration-resistant prostate cancer (mCRPC) to assess safety, how the drugs behave in the body, and preliminary effectiveness. This Phase 1, open-label study aims to find the best doses of KTX-2001 alone and with darolutamide for future studies. Participants will receive increasing doses of KTX-2001 either alone or together with darolutamide, an oral androgen receptor pathway inhibitor. The study is divided into parts where some men receive just KTX-2001 and others receive the combination treatment. Dosing will be carefully increased to monitor safety and determine the maximum tolerated dose. Participants will undergo scans and biopsies to confirm metastatic disease and monitor progress. Safety assessments include checking for dose-limiting toxicities within 21 days. Laboratory tests will evaluate kidney, liver, and blood function, while researchers track how the drugs move through and affect the body. The study monitors treatment effects and safety over time to guide future research.

Researchers are investigating ways to prevent cytomegalovirus (CMV) infection in children and adolescents who have received a kidney transplant and weigh less than 40 kilograms. This Phase 1 study aims to understand how the drug letermovir behaves in the body over time and to evaluate its safety and tolerability in this young population. Participants receive letermovir orally, either as tablets or pellets, or through a gastrostomy or nasogastric tube if pellets are used. The treatment is given once daily for seven consecutive days. This study is open-label and single-arm, meaning all participants receive the same treatment, and the study monitors them closely throughout this period. During the study, participants will have blood samples collected before the first dose and at several points up to 24 hours after dosing on Day 7 to measure how the drug is processed by the body. Researchers will also monitor kidney function stability, CMV DNA levels, and any side effects to assess safety. The study focuses on children and adolescents younger than 18 years and weighing between 2.5 and less than 40 kilograms, with a total participation time covering at least seven days of treatment and associated assessments.

Researchers are evaluating sotatercept as a potential treatment for pulmonary arterial hypertension (PAH), a condition where blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and overworking the heart. PAH symptoms include difficulty breathing and reduced ability to be active. Current standard treatments address symptoms but do not stop disease progression. This Phase 3 study focuses on the long-term safety and tolerability of sotatercept when added to standard PAH therapy. Participants in this long-term follow-up study receive sotatercept through subcutaneous injections every three weeks. Only individuals who completed prior sotatercept PAH studies without early discontinuation may join. This study continues the observation and assessment of participants over an extended period to learn about the effects and safety of sotatercept combined with background PAH treatments. During the study, participants will be regularly monitored for adverse events, treatment discontinuations, and the presence of anti-drug antibodies for up to approximately 90 months. Laboratory tests will evaluate blood components such as platelets, hemoglobin, creatinine, bilirubin, and liver enzymes. Changes from baseline in body weight, blood pressure, and electrocardiogram readings will also be tracked. The study involves adherence to visit schedules and compliance with study procedures to ensure comprehensive long-term safety data collection.

Researchers are evaluating the safety, effectiveness, best dose, and how the body processes (pharmacokinetics) an investigational drug called BNT326. This study includes people with advanced solid tumors that are metastatic, recurrent, or have progressed after previous treatments. The investigation is divided into two parts: Part 1 tests BNT326 alone, and Part 2 studies BNT326 alone or combined with other immunotherapy drugs, including pumitamig (BNT327). Participants have specific tumor types like melanoma, non-small cell lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer, among others. In Part 1, participants receive BNT326 by intravenous infusion in various groups based on cancer type and prior treatments. Part 2 involves BNT326 given alone or with pumitamig, also by intravenous infusion, in several defined cancer groups. Some groups are randomized to receive different dose levels or combinations to find the optimal treatment plan. The study includes a screening phase, treatment phase lasting up to 24 months or until progression or unacceptable side effects, a safety follow-up, efficacy follow-up, and long-term survival monitoring, totaling about 38 months for Part 1 and 48 months for Part 2. During the study, participants undergo regular assessments including measuring tumor response using RECIST criteria, monitoring for side effects and serious adverse events up to months after treatment ends, and measuring drug levels in the blood. Researchers track treatment interruptions or discontinuations due to side effects and evaluate dose-limiting toxicities. Tumor tissue samples are required before enrollment. Safety and effectiveness data are collected throughout treatment and follow-up periods to understand how well BNT326 works alone or combined and its safety profile.