Washington University in St. Louis / WashU Medicine

This research aims to understand the immune response in adults who are symptomatic with confirmed influenza or COVID-19 infections. It compares people who have and have not been vaccinated against these viruses within the past year, focusing on how their immune systems react to acute respiratory infections caused by these viruses. Participants include those with active symptoms and a control group who have been vaccinated but not infected recently. Participants are grouped based on their infection status and vaccination history, including uninfected vaccinated individuals and those infected with either influenza or SARS-CoV-2, with or without recent vaccination. All participants attend five visits for data collection and sample testing, including blood, saliva, and nasal swabs, at enrollment, day 7, between days 10 to 28, day 90, and day 180. An optional bronchoscopy procedure, including bronchoalveolar lavage and endobronchial biopsy, may be performed twice in some participants, along with chest X-rays, though this is not required. During the study, participants undergo immune system evaluations through various sample collections and tests at specified time points to measure antibody levels and T cell responses in different body areas. Researchers monitor immune response changes from the time of infection through six months after enrollment. Safety screenings occur for those opting for bronchoscopy to ensure suitability. The entire study participation lasts approximately six months with multiple visits and assessments focused on understanding immune dynamics in respiratory viral infections.

Researchers are investigating the connection between donor-derived cell-free DNA DD-cfDNA levels, HLA antibodies in blood, and the Molecular Microscope Diagnostic System MMDx results in kidney transplant patients. The study aims to improve the detection of kidney transplant rejection, as current tests like creatinine, urine protein, histology, and donor-specific antibody tests often miss rejection or produce false results. MMDx offers a molecular assessment of rejection and injury, and the new Prospera DD-cfDNA blood test is being evaluated against these methods to better identify different types of rejection and kidney injury. The study involves patients with functioning kidney transplants who are undergoing biopsies for clinical reasons. Blood samples will be taken to measure DD-cfDNA using the Prospera test and to assess HLA antibodies centrally. Kidney biopsy samples will also be analyzed using the MMDx system. Researchers will compare DD-cfDNA levels at the time of indication biopsies with MMDx results, histology, and HLA antibody status to calibrate and evaluate the accuracy of the Prospera test. Participants will contribute blood samples and kidney biopsy results that are collected as part of their standard care. The study will analyze about 600 blood samples and 300 biopsies, with data collected over several years. Researchers will measure outcomes related to the calibration of the Prospera test for detecting T cell-mediated rejection, antibody-mediated rejection, and kidney injury. The study also assesses whether the Prospera blood test can replace kidney biopsy as a less invasive method for monitoring transplant rejection and injury.

Researchers are evaluating whether adding infusions of a special type of immune cells called natural killer NK cells to the chemotherapy regimen gemcitabine and docetaxel GEMDOX can improve outcomes for children and young adults with sarcomas that have come back or did not respond to previous treatments. This study aims to determine the safety and effectiveness of this combined treatment in relapsed or refractory pediatric sarcomas, including osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and other soft tissue sarcomas. The study is a multi-center, phase 1 and 2 trial with ongoing safety and toxicity analysis conducted by Nationwide Childrens Hospital. Participants receive up to 8 cycles of treatment, each lasting 21 days. Each cycle includes intravenous gemcitabine on days 1 and 8, docetaxel on day 8, oral dexamethasone on days 7 to 9 to prevent side effects, pegfilgrastim on day 9 to help white blood cells recover, and intravenous TGF-beta imprinted TGFb2i, ex vivo expanded universal donor NK cells on day 12. Tumor response is checked after cycles 2, 4, 6, and 8. The study carefully monitors for toxicities related to the combined treatment and tracks how well the NK cells persist in the body and relate to clinical outcomes. During the trial, participants undergo regular assessments including tumor measurements using the RECIST 1.1 criteria every two cycles, evaluation of treatment-related side effects, and laboratory tests to monitor blood counts and organ function. Safety and disease progression are followed for 3 to 5 years. The study also evaluates six-month progression-free survival to understand how well the treatment controls the cancer. Overall, participants will be closely monitored throughout the study and during long-term follow-up to assess the treatments effects and safety.

Researchers are evaluating the long-term safety, tolerability, and effectiveness of Givinostat in patients with Duchenne Muscular Dystrophy DMD who have already participated in previous Givinostat studies. This open-label trial focuses on patients who have been previously treated with Givinostat, aiming to monitor ongoing effects and any adverse events over an extended period. Participants will take an oral suspension of Givinostat 10 mgmL twice daily while in a fed state. The starting dose will match what each patient received at the end of their prior Givinostat study and may be adjusted based on their weight and safety monitoring, especially platelet counts. Dose reductions or treatment interruptions may occur if certain safety concerns arise, such as severe diarrhea, serious adverse events, or specific blood count thresholds. The study includes weekly platelet monitoring during the first month and biweekly during the second month, with adjustments as needed. Throughout the study, participants will be closely monitored with regular evaluations of safety and tolerability, including blood tests to check platelet counts, white blood cells, hemoglobin, and heart rhythm QTcF intervals. Researchers will track the incidence of treatment-emergent adverse events over an average of one year. The investigator will manage any safety concerns and follow participants until any issues resolve or stabilize, after which participants will complete the study with an end-of-study visit. The total participation duration may vary based on individual progress and safety outcomes.

Researchers are evaluating the safety and effectiveness of Raludotatug Deruxtecan R-DXd in adults with platinum-resistant, high-grade ovarian, primary peritoneal, or fallopian tube cancer. This study includes a Phase 2 dose-optimization part to find the best dose based on safety and effectiveness, followed by a Phase 3 part comparing R-DXd to chemotherapy chosen by the investigator. The study targets tumors that overexpress CDH6, a protein that R-DXd specifically binds to. Participants are randomly assigned to receive intravenous R-DXd at various doses every three weeks or an investigators choice of chemotherapy drugs including paclitaxel, pegylated liposomal doxorubicin, or topotecan. The Phase 2 portion focuses on determining the optimal dose, while the Phase 3 portion compares the recommended dose with standard chemotherapy. Treatments are given through IV infusions according to the assigned group. During the study, participants undergo scheduled visits for drug administration, safety monitoring, and evaluations including imaging scans to assess tumor response. Researchers measure outcomes such as objective response rate, progression-free survival, overall survival, duration of response, symptom changes, and pharmacokinetics over periods up to 40 months. Safety is closely monitored through adverse event tracking and laboratory tests, with participants followed until the studys completion in 2030.

Researchers are evaluating the safety and effectiveness of Non-Ischemic Heart Preservation NIHP using the XVIVO Heart Preservation System XHPS to preserve and transport extended criteria donor hearts for transplantation. This continuation of the PRESERVE IDE trial aims to provide more data on the XVIVO Heart Assist Transport System XHAT while a Post-Market Approval application is under review. The study focuses on donor hearts that may not meet current standard acceptance criteria but are intended for transplantation. The trial uses the XHAT System device to preserve donor hearts through Non-Ischemic Heart Preservation. This approach is applied to hearts meeting extended criteria, such as longer cross clamp times or specific heart function measures. The study is single-arm, open-label, and prospective, allowing patients and physicians access to the device during the continued access protocol period. Participants are individuals aged 18 years or older listed for heart transplantation. Researchers will monitor patient survival rates up to one year after transplantation and treatment success at 30 days post-transplant. Assessments include clinical evaluations and safety monitoring throughout the study. The total participation duration varies depending on transplant timing and follow-up, with researchers tracking outcomes related to heart preservation and transplant success.

Researchers are studying the long-term safety of lutetium 177Lu vipivotide tetraxetan, also called AAA617 or 177Lu-PSMA-617, in adult men with prostate cancer. This post-marketing Phase IV study aims to better understand the lasting effects and possible serious side effects of AAA617 in those who have received it in prior Novartis clinical trials. The focus is on monitoring known or potential risks over many years. Participants have already received at least one dose of AAA617 in earlier clinical trials and will join this long-term follow-up study without receiving any new treatments. The study involves visits every 6 to 8 months for up to 10 years after the first dose of AAA617, with no study treatment given during this time. The number of visits depends on when participants enroll following their initial treatment. During each visit, researchers will monitor selected side effects and laboratory tests to track safety outcomes. The main measurements include the number and percentage of participants experiencing selected adverse events and serious adverse events. They will also record deaths and measure radiation doses in organs like the kidney. Participants will be followed until death, lost to follow-up, or completion of 10 years from first AAA617 dose, whichever comes first.

Researchers are evaluating whether delivering a short period of electrical stimulation during surgical repair can speed up nerve healing in people with digital nerve injuries. The study focuses on patients requiring surgical intervention to repair nerve damage in their fingers and aims to assess the recovery of nerve function after treatment. Participants will receive standard surgical repair of their digital nerve injury as determined by their surgeon. During the surgery, one group will receive an additional 10-minute dose of therapeutic electrical stimulation to the repaired nerve. The study compares outcomes between those who receive standard care alone and those who receive the extra electrical stimulation during surgery. Throughout the study, participants will be assessed over a period from 2 weeks up to 9 months after surgery. Researchers will use tests such as Two Point Discrimination, Semmes-Weinstein Monofilament Test, Visual Analog Scale VAS, quick Disabilities of Arm, Hand, and Shoulder quickDASH, and the Michigan Hand Outcomes Questionnaire MHQ to measure nerve function, sensation, pain, and hand disability. Participants will be monitored closely to evaluate the speed and quality of nerve recovery.

Researchers are evaluating the safety and biological effects of tofersen in adults who have amyotrophic lateral sclerosis ALS without mutations in the SOD1 gene. The study focuses on whether tofersen reduces levels of neurofilament light chain NfL in the blood and cerebrospinal fluid CSF, how well participants tolerate the treatment, and its impact on clinical outcomes and quality of life. Tofersen is already approved for treating SOD1-ALS, and this trial aims to explore its effects in non-SOD1 ALS cases. Participants will receive 100 mg of tofersen via lumbar puncture at eight time points over 24 weeks Weeks 0, 2, 4, 8, 12, 16, 20, and 24. After the dosing period, participants will have two follow-up visits at Weeks 28 and 32. The study involves only one group receiving tofersen, with no placebo or comparison groups. During the trial, participants will complete various questionnaires and undergo outcome assessments such as strength and breathing tests. Researchers will monitor safety and tolerability, measure changes in neurofilament levels, and track clinical and quality-of-life outcomes. The primary measurement is the proportion of participants with at least a 30% reduction in plasma NfL from baseline to Week 28, with additional safety monitoring continuing through study completion around eight months.

Researchers are evaluating the safety, tolerability, and effectiveness of Descartes-08 in children, adolescents, and young adults aged 12 and older with childhood-onset autoimmune diseases including systemic lupus erythematosus, ANCA-associated vasculitis, juvenile myasthenia gravis, and juvenile dermatomyositis. This study is designed as a two-part Phase 12 trial to find the maximum tolerated dose and assess treatment effects in these conditions. The study includes two parts In Part 1, three different doses of Descartes-08 will be given to small groups of participants to establish the maximum tolerated dose. In Part 2, this dose will be administered as six weekly infusions to up to 10 participants in each disease category, given in an outpatient setting. The treatment is delivered by infusion and monitored closely to determine safety and response. Participants will be involved in regular visits during and after treatment to monitor safety and disease status. Assessments include monitoring for serious adverse events at specific days and months, along with blood tests and clinical evaluations over a period extending up to 12 months. Researchers will track the maximum dose tolerated and the frequency of treatment-related adverse events to understand the safety profile of Descartes-08 in these young patients.