Pittsburgh

Researchers are evaluating remibrutinib (LOU064) in adolescents aged 12 to under 18 years who have chronic spontaneous urticaria (CSU) that is not well controlled by H1-antihistamines. This Phase 3 trial aims to assess the effectiveness, how the drug is processed in the body, and safety of remibrutinib compared to a placebo. The study also intends to gather long-term data on how well remibrutinib works and its safety over several years after treatment ends. The trial includes three periods. First, the core period is a 24-week double-blind phase where about two-thirds of participants receive remibrutinib and one-third receive placebo, with about 10 site visits over approximately 32 weeks. Next is an optional open-label extension lasting from one to three years, where participants who completed the core period may receive remibrutinib or enter an observational treatment-free phase depending on their symptoms. Participants may cycle through treatment and observational periods up to six times. Finally, an optional long-term treatment-free follow-up can last up to three years with one site visit and up to four phone calls. During the study, participants undergo assessments including changes in urticaria activity scores (UAS7), itching severity (ISS7), and hive severity (HSS7) measured from baseline to 12 weeks. Regular visits monitor safety, symptoms, and drug effects. The study tracks these measures to understand remibrutinib's impact on CSU symptoms and overall safety profile during and after treatment, with total participation potentially lasting several years.

Researchers are comparing two types of maxillary expanders used to widen the upper jaw in children aged 8 to 13 years who have maxillary transverse deficiency. The study aims to evaluate whether the newer 3D-printed expander, designed on a computer and printed in metal, works as well as the traditional laboratory-made expander, while potentially providing greater comfort to patients. This randomized controlled clinical trial involves participants from orthodontic clinics at the Medical University of South Carolina and the University of Pittsburgh School of Dental Medicine. Participants will be randomly assigned to receive either the conventional hand-made laboratory expander or the 3D-printed expander. Both devices are used to expand the upper jaw, with the 3D-printed version incorporating advanced digital design and printing technology. The treatment will be monitored over a period of 6 months to assess the effects of each expander. During the study, participants will attend regular clinical follow-up visits where photos, X-rays, and dental photo scans will be taken to observe the progress of the maxillary expansion. Additionally, participants will complete online questionnaires with help from their parents or guardians to report their quality of life and any pain or discomfort experienced at various times. The main outcome measured is the dimension of the anterior midpalatal suture opening two weeks after starting treatment. This study also monitors safety and comfort throughout the 6-month period.

Researchers are evaluating a combination of three treatments—9-ING-41 (elraglusib), retifanlimab, and modified FOLFIRINOX chemotherapy—in patients with advanced pancreatic adenocarcinoma who have not received prior systemic therapy for their advanced disease. This Phase 1b study explores whether blocking glycogen synthase kinase-3 beta (GSK-3β) with 9-ING-41 alongside PD-1 inhibition by retifanlimab plus chemotherapy can provide enhanced anti-tumor effects. Retifanlimab has shown safety and effectiveness in other cancers, and 9-ING-41 has demonstrated acceptable safety in previous studies, but their combined use with mFOLFIRINOX is new and being tested for safety and tolerability. The study begins with a safety lead-in cohort of 6 patients receiving the combination treatment, with dose adjustments if needed based on safety results. After confirming a safe dose, an expansion cohort will enroll additional patients, with the total number not exceeding 12. Retifanlimab is given intravenously every 4 weeks, and 9-ING-41 is administered alongside the components of mFOLFIRINOX chemotherapy, which includes oxaliplatin, leucovorin, irinotecan, and 5-fluorouracil. The treatments are given as frontline therapy for advanced pancreatic cancer. Participants will have scheduled visits to monitor their health, laboratory tests to assess blood, liver, kidney, and pancreatic enzymes, and tumor evaluations using imaging and other assessments. Researchers will track dose limiting toxicities up to 28 days after treatment starts to evaluate safety. Patients must provide tumor tissue samples for molecular profiling. The study also monitors for adverse events and overall treatment tolerability during the treatment period and follow-up. Total study duration depends on treatment cycles and safety assessments.

Researchers are investigating cocaine use disorder (CUD), a chronic condition marked by frequent relapses and abstinence periods. This study focuses on understanding neurochemical changes, particularly involving the brain's stress and anti-stress systems, to help develop medications that prevent relapse. The trial explores the role of nociceptin (N/OFQ) and its receptor (NOP) in counteracting stress-related brain effects and how their dysfunction may contribute to relapse in CUD patients. Participants will undergo brain imaging using [11C]NPA positron emission tomography (PET) scans at baseline and after receiving oral d-amphetamine (0.5 mg/kg). The study includes a baseline [11C]NOP-1A PET scan (completed in a related aim) to measure NOP receptor binding. The amphetamine challenge helps measure dopamine release in the brain's striatum, linking dopamine activity to NOP receptor expression and stress-response mechanisms. These imaging sessions aim to clarify how stress and reward systems interact in CUD. During the study, participants will have multiple PET scans and receive oral amphetamine. Researchers will assess dopamine release by comparing brain scans before and 2.5 to 3 hours after amphetamine intake. Medical and psychiatric evaluations will ensure safety, and follow-up over 12 weeks will track relapse risk. The primary outcome is the change in dopamine receptor binding potential after amphetamine. This early phase 1 trial helps deepen understanding of brain changes in CUD and potential relapse mechanisms.

Researchers are evaluating the progress of chronic venous leg ulcers in adults using a non-bordered foam dressing called ALLEVYN Non-Adhesive. This investigation is prospective, open, multi-center, and interventional without comparison groups. The study aims to track wound changes over a 6-week period or until the wound heals, focusing on both objective wound area measurements and subjective wound condition assessments. Twenty participants will be recruited from up to six centers in the US and Canada, all diagnosed with moderate to large exuding venous leg ulcers. Participants will use the ALLEVYN Non-Adhesive dressing, which features a breathable top film, a highly absorbent foam core, and a non-adhesive wound contact layer designed for fragile and sensitive skin. The dressing will be worn continuously and changed at weekly intervals for up to six weeks or until the wound heals. The intervention follows local standards of care for wound management. During the study, participants will attend seven visits: a baseline visit and six weekly follow-ups. Each visit will include assessments of wound progression, dressing performance, and participant experiences, including pain, comfort, and quality of life. Safety will be monitored throughout the study. The main outcome measured is the wound's progress from the initial visit to the last follow-up, with a maximum treatment duration of 44 days or until healing.

Researchers are evaluating the healing progress of chronic wounds, specifically venous leg ulcers and diabetic foot ulcers, using an absorbent dressing called Mepilex Up. The study is designed as a prospective, open, multi-center, interventional, non-comparative trial involving about 68 participants across up to 8 centers in the US. The goal is to monitor wound area changes and wound condition over a 6-week period following local standard care. Participants will use the Mepilex Up dressing, which is designed to absorb exudate, maintain a moist healing environment, and minimize pain and skin trauma during dressing changes. The dressing contains a soft silicone wound contact layer, a flexible absorbent foam pad, and a breathable but waterproof outer film. Participants will wear the dressing for up to six weeks or until their wound heals, with dressings changed weekly during scheduled visits. Participants will attend seven visits: one baseline and six weekly follow-ups to assess wound healing progress, dressing performance, pain, comfort, and quality of life. Safety will be monitored throughout. One target wound per participant will be followed, with measurements taken from baseline to the last follow-up, up to a maximum of 44 days or until healing occurs.

Researchers are evaluating the safety and effectiveness of ifinatamab deruxtecan (I-DXd) alone or combined with other treatments in people with metastatic castration-resistant prostate cancer (mCRPC). This study aims to understand how well patients tolerate the treatment, find a safe dose for combining I-DXd with other drugs, and measure prostate-specific antigen (PSA) levels during treatment. The study is part of a larger master screening protocol and includes patients with confirmed prostate adenocarcinoma who have progressive disease despite prior therapies. Participants receive treatments including I-DXd given through intravenous infusion, sometimes combined with other drugs such as docetaxel (IV), MK-5684, abiraterone, or enzalutamide (all oral). Before each I-DXd dose, patients take premedication to prevent nausea and vomiting. The study includes both a safety lead-in phase and an efficacy phase, with ongoing monitoring for side effects and tolerability. The combination therapies are carefully dosed and scheduled according to the study protocol. During the study, participants undergo regular assessments to monitor side effects, measure PSA response, and track any dose-limiting toxicities. Safety is closely followed, particularly during the first 21 days for combination treatments, and throughout up to 54 months for long-term outcomes. Researchers also observe if participants discontinue treatment due to adverse events. The study requires ongoing visits and evaluations to ensure participant health and collect data on treatment effects over time.

Researchers are evaluating the safety and preliminary effectiveness of T3011, a treatment given directly into tumors, alone and combined with pembrolizumab, an intravenous medication, in adults with advanced or metastatic solid tumors. This Phase 1/2a open-label study focuses on several types of cancers including melanoma, head and neck squamous cell carcinoma, sarcoma, cutaneous squamous cell carcinoma, and non-small cell lung cancer. The study aims to find the best dose of T3011 and understand its safety when used alone or with pembrolizumab. The study begins with a Phase 1 dose escalation to test increasing doses of T3011 using a 3+3 design. After determining the recommended dose, Phase 2a Part 1 will evaluate T3011 alone in different cancer types across multiple arms, while Phase 2a Part 2 will assess the combination of T3011 with pembrolizumab in participants with metastatic non-small cell lung cancer. T3011 is given as an intratumoral injection up to 4mL every two weeks, and pembrolizumab is given intravenously every three weeks when combined. A rollover arm allows participants whose disease progresses on T3011 alone to receive the combination treatment. Participants will be closely monitored for safety and treatment effects for up to two years from the first dose of T3011. Assessments include tumor measurements, biopsies, laboratory tests, and evaluation of adverse effects. The study records the tolerability of escalating doses and the combination treatment, tracking disease progression and response. Participants must attend scheduled visits for injections, monitoring, and evaluations throughout the study period.

Researchers are looking for new medicines to prevent HIV-1 (Human Immunodeficiency Virus Type 1) infection. The goals of this study are to learn: * If taking MK-8527 once a month works to prevent HIV-1 infection as well as or better than a standard (usual) pre-exposure prophylaxis (PrEP) taken once a day * About the safety of MK-8527 and if people tolerate it

Researchers are evaluating treatments for breast cancer that is hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-), specifically in cases where the cancer is either locally advanced and cannot be removed by surgery or has spread to other parts of the body (metastatic). The study aims to determine if patritumab deruxtecan (also called HER3-DXd or MK-1022) helps patients live longer overall or without the cancer growing compared to chemotherapy or trastuzumab deruxtecan. This is a Phase 3 clinical trial focusing on this particular type of breast cancer. Participants receive one of several treatments: patritumab deruxtecan through intravenous infusion, chemotherapy options like paclitaxel or nab-paclitaxel via IV, oral capecitabine tablets, liposomal doxorubicin via IV, or trastuzumab deruxtecan via IV infusion. The study compares the effects of patritumab deruxtecan alone to the treatment chosen by the physician. Treatments are administered according to standard dosing schedules during the trial. During the study, participants are monitored for how long they live without the cancer progressing (up to about 45 months) and overall survival (up to about 85 months). Researchers assess disease status through imaging and other evaluations. Participants have regular check-ups to monitor health, treatment effects, and any side effects. The study tracks treatment response and safety over the extended follow-up period to understand the benefits and risks of the therapies.