Fayetteville

Researchers are evaluating the safety and performance of the Canary canturioTM te tibial extension in patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis. This prospective observational study compares the Canary canturioTM te device to the legally marketed Zimmer Persona Personalized Knee System with a 14 mm x +30 mm stem extension. The main goal is to assess the nature, severity, and frequency of safety risks within five years after surgery, including complications like revision, loosening, fractures, and radiologic changes. Participants are divided into two groups: one receiving the Zimmer Persona Personalized Knee System with the Canary canturioTM te tibial extension, and the other using the Zimmer Persona Personalized Knee System with a traditional 14 mm x +30 mm stem extension. The study monitors safety outcomes over five years post-TKA. Secondary measures include the collection of step-count and gait data, pain and functional assessments using standardized scores, and evaluation of the device's reliability and accuracy in measuring walking speed and gait parameters at one and two years post-surgery. During the study, patients will be monitored for adverse events and safety risks related to their knee implant. Data collection includes daily step counts, gait activity, and clinical assessments such as the Knee Injury and Osteoarthritis Outcome Score (KOOS - JR), Numeric Pain Rating Scale, and quality-of-life questionnaires. A subgroup undergoes detailed gait lab assessments to evaluate device performance. The total follow-up period spans five years, allowing researchers to observe long-term outcomes and device safety.

Researchers are evaluating a drug called sigvotatug vedotin alone and in combination with pembrolizumab, with or without chemotherapy, to determine its safety and effects in people with various advanced solid tumors. This Phase 1 study includes participants with specific cancers like non-small cell lung cancer, head and neck squamous cell cancer, HER2-negative breast cancer, esophageal cancers, ovarian cancer, and others. The trial aims to find out the side effects of sigvotatug vedotin and whether it can treat these solid tumors effectively. The study is divided into four parts. Part A focuses on finding the right dose of sigvotatug vedotin. Part B tests the safety and effectiveness of that dose. Parts C and D look at the safety and effectiveness of sigvotatug vedotin combined with pembrolizumab alone or with chemotherapy drugs carboplatin or cisplatin. Participants receive these drugs intravenously, with pembrolizumab given every 3 or 6 weeks and chemotherapy every 3 weeks depending on the drug. During the study, participants undergo tumor biopsies, physical exams, and disease assessments to monitor treatment effects. Researchers track side effects, lab abnormalities, and dose-limiting toxicities for up to 30-37 days after the last dose of sigvotatug vedotin, and for up to 3 years after pembrolizumab treatment. The study follows participants with regular safety monitoring and evaluations of tumor response throughout the trial.

Researchers are evaluating the effectiveness and safety of upadacitinib at different doses in adults with moderate to severe atopic dermatitis (AD) who have not responded adequately to dupilumab treatment. AD is a skin condition causing rash and itching due to inflammation, and some people require systemic treatments beyond topical therapies. This phase 3b/4 study aims to provide data on upadacitinib's impact on AD symptoms in this specific population. The study is conducted in two open-label periods. In Period 1, participants are randomly assigned to receive either upadacitinib 15mg orally once daily or dupilumab 300mg by subcutaneous injection every two weeks. After two weeks, those on upadacitinib 15mg may have their dose increased to 30mg based on their response. Period 2 lasts 24 weeks, during which participants either continue their assigned dose or switch doses depending on their eczema severity scores. The entire treatment duration is 32 weeks with follow-up for 30 days after treatment ends. Participants will undergo regular visits at hospitals or clinics for medical assessments, blood tests, side effect monitoring, and questionnaires to evaluate treatment effects. The main outcome measured is the number of participants achieving at least a 90% improvement in their eczema severity index by week 8. The study includes a 35-day screening period before treatment begins and monitors safety and efficacy throughout the study duration.

Researchers are evaluating the safety and effectiveness of upadacitinib in treating adults and adolescents with moderate to severe hidradenitis suppurativa (HS) who have not responded to or cannot tolerate anti-tumor necrosis factor (TNF) therapy. HS is an inflammatory skin disease causing painful lesions in areas such as the underarms, groin, and anal/genital regions. This phase 3, double-blind study involves approximately 1328 participants worldwide and aims to monitor disease activity and adverse events over time. Participants will receive oral tablets of either upadacitinib or placebo once daily during Period 1 and Period 2, lasting a total of 36 weeks. In Period 1, participants are randomly assigned to one of two treatment groups, with a 50% chance of receiving placebo. Based on results and placement in earlier periods, participants enter Period 2 with six potential treatment groups. Eligible participants from these periods may continue into Period 3, a long-term extension lasting 68 weeks, continuing the same daily oral treatment. Following the treatment periods, participants will be followed for approximately 30 days. During the study, participants will attend regular outpatient visits for medical assessments, monitoring for side effects, and completing questionnaires. Researchers will measure the percentage of participants achieving a clinical response called HiSCR 50 from baseline to week 16 and track adverse events up to approximately week 108. The study may require a higher treatment commitment compared to usual care, but provides close monitoring of disease activity and safety throughout all study phases.

This research aims to evaluate the effects of povorcitinib on reducing itch and improving skin lesions in adults with prurigo nodularis, a chronic skin condition characterized by itchy nodules. The study is a Phase 3 trial designed to assess the safety and efficacy of this treatment compared to a placebo in participants aged 18 to 75 years with a confirmed diagnosis of prurigo nodularis lasting at least three months. Participants will receive either oral povorcitinib tablets or placebo tablets as part of the randomized, double-blind study. Key eligibility includes having significant itch severity and at least 20 pruriginous lesions on multiple body regions. The study monitors the treatment effects over 24 weeks, focusing on improvements in itch intensity and skin lesion severity. During the study, participants will be closely monitored for changes in their itch scores and skin condition. Researchers will assess the proportion of participants achieving specified improvements by Week 24. Safety and tolerability will also be evaluated throughout the trial. Participants will undergo regular assessments including clinical evaluations, laboratory tests, and adherence monitoring to track progress and any side effects over the course of the study.

This research aims to evaluate the safety and effectiveness of ruxolitinib cream in children aged 2 to 11 years with nonsegmental vitiligo, a condition that causes loss of skin color in patches. The study is a Phase 3 trial focusing on this pediatric population to better understand how well the treatment works and how safe it is for young patients. Participants will be randomly assigned to receive either ruxolitinib cream or a matching vehicle cream, both applied as a thin layer twice daily to the affected skin areas. The treatment is topical and focuses on areas of skin depigmentation, including the face and other body parts. The study measures progress over 24 weeks to determine the proportion of participants who achieve significant improvement in facial vitiligo. Throughout the study, participants will have regular assessments including skin evaluations and safety monitoring. Researchers will track changes in the affected skin areas using the Facial Vitiligo Area Scoring Index. Participants must stop all other vitiligo treatments before starting and during the study. Safety follow-ups will continue after treatment to ensure participant well-being and gather comprehensive data on treatment effects.

Researchers are investigating the safety and effectiveness of Dato-DXd combined with osimertinib or alone compared to platinum-based doublet chemotherapy in treating adults with epidermal growth factor receptor-mutated (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC). This Phase III, open-label study includes participants whose disease has worsened despite prior osimertinib treatment. The goal is to evaluate progression-free survival (PFS) over up to 2.5 years. Participants are randomly assigned to one of three groups: Dato-DXd plus osimertinib, Dato-DXd alone, or platinum-based doublet chemotherapy. Dato-DXd and chemotherapy drugs (pemetrexed, carboplatin, or cisplatin) are given by intravenous infusion, while osimertinib is taken orally. Treatment continues until the cancer progresses based on imaging, unacceptable side effects occur, or other reasons require stopping treatment. After stopping the study drugs, participants will have an end-of-treatment visit within 35 days and safety follow-up about one month later. During the trial, researchers will monitor participants with radiological scans and assess progression-free survival. Safety evaluations will continue after treatment ends to detect any side effects. The study includes adults aged 18 to 130 years with good performance status and adequate organ function who have progressed on prior osimertinib therapy. The total study duration includes treatment and follow-up periods to ensure thorough assessment of treatment effects and safety.

Researchers are evaluating the safety and effects of the study medicine PF-07799544, alone or combined with PF-07799933, as a potential cancer treatment for adults with advanced solid tumors. This trial involves participants with metastatic or recurrent solid tumors (excluding colorectal cancer) that have a BRAF V600 mutation and who have received prior cancer treatments as assigned. Phase 1a of the study, which involved PF-07799544 alone, is closed for enrollment, and the current Phase 1b focuses on combination therapy with both medicines. All participants in Phase 1b will take both study medicines as tablets by mouth twice daily at home. Treatment will continue until the cancer no longer responds, unacceptable side effects occur, or for up to two years. Participants may continue therapy beyond two years if appropriate. The study is designed to monitor the safety and potential effectiveness of these treatments in this patient population. Participants will be assessed for dose limiting toxicities, treatment-emergent adverse events, and clinically significant changes in laboratory tests, vital signs, and physical exams during the first 21 days and up to 28 days after the last dose. The overall response rate will be measured for up to two years. Safety and treatment effects will be carefully monitored throughout, with the goal of understanding how these medicines impact patients with BRAF-mutant advanced solid tumors.

Researchers are evaluating the safety and effects of the study medicine PF-07799933 in people aged 16 and older who have advanced solid tumors with specific BRAF gene alterations. The trial includes participants whose cancers have progressed despite available treatments. This phase 1 open-label study aims to learn about the tolerability, pharmacokinetics, and anti-tumor activity of PF-07799933 given alone and combined with other study medicines. All participants will receive PF-07799933 tablets twice daily. Depending on the tumor type and study part, some participants may also receive binimetinib tablets twice daily, or cetuximab injections weekly or every two weeks in the clinic. Participants with colorectal cancer may also receive mFOLFOX6 chemotherapy, which includes fluorouracil, leucovorin, and oxaliplatin given intravenously. The study involves dose escalation and expansion phases, with treatment lasting about 2 years. Participants will attend regular clinic visits for monitoring during treatment. Researchers will assess dose-limiting toxicities, adverse events, changes in laboratory tests, vital signs, and physical exams from baseline through 28 days after the last dose. Dose interruptions, modifications, and discontinuations due to side effects will be tracked up to 2 years. The overall response rate to treatment will also be measured during this period.

Researchers are evaluating the study medicine PF-08046054 compared to the standard chemotherapy drug docetaxel in adults with non-small cell lung cancer (NSCLC) that has spread or cannot be removed with surgery or radiation. Participants must have PD-L1 expression on 1% or more of their tumor cells and have experienced cancer progression during or after treatment with PD-L1 or PD-1 inhibitors, platinum-based chemotherapy, and targeted therapies for those with known genetic mutations. The trial is a Phase 3 randomized study to better understand how well PF-08046054 works alone compared to docetaxel alone. Participants will be randomly assigned to receive either PF-08046054 or docetaxel. Those in the PF-08046054 group will get intravenous (IV) infusions twice every 21-day cycle, while those in the docetaxel group will receive one IV infusion every 21 days. The treatment period may last up to 5 years if their NSCLC responds to the therapy. No other treatments are combined during the study period. Throughout the study, participants will have regular clinic visits for evaluations and monitoring to see how they respond to the treatment. Researchers will collect information on overall survival over approximately 5 years. They will also monitor safety and disease progression during these visits to understand the long-term effects and benefits of the treatments.