Hartford

Researchers are evaluating the safety, effectiveness, best dose, and how the body processes BNT326 when used alone or combined with other immunotherapy drugs in adults with advanced solid tumors. These tumors are either metastatic, recurrent without further treatment options, or have relapsed after previous therapy. The study includes patients with different types of advanced cancers such as melanoma, lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer. In Part 1, participants receive BNT326 alone across several cancer-specific groups, including cutaneous melanoma, non-small cell lung cancer with or without specific mutations, rare melanomas, advanced tumors, and cervical cancer. Part 2 evaluates BNT326 alone or combined with another immunotherapy drug called pumitamig. Participants are assigned to different dose levels, sometimes randomly, depending on their cancer type and group. The study includes a screening period, treatment for up to 24 months or until progression or other reasons, and follow-up periods. During the study, participants undergo assessments including tumor tissue sampling, monitoring of treatment side effects, blood tests to measure drug levels, and evaluations of tumor response and survival. Safety is closely followed up to 42 or 90 days after treatment ends, with longer-term monitoring for up to 38 months Part 1 or 48 months Part 2. Participants overall response rates, adverse events, and pharmacokinetics are key outcomes. The study is sponsored by BioNTech SE and includes open-label, adaptive design across two phases.

Researchers are evaluating AV-380, an immunoglobulin G1 monoclonal antibody designed to bind human growth differentiation factor 15 GDF-15, a cytokine involved in cancer-induced cachexia. This phase 1B open-label dose escalation study aims to assess the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of AV-380 in cancer patients who have cachexia and elevated GDF-15 levels. Participants have metastatic solid tumors and are actively receiving standard of care chemotherapy. Participants receive AV-380 through intravenous infusion in ascending dose cohorts alongside their standard chemotherapy treatments. The study includes a dose escalation phase where the safety and appropriate dosage of AV-380 are evaluated. This phase allows researchers to monitor the effects of increasing doses of AV-380 over a study period of up to 4 months while patients continue their usual cancer therapies. During the study, participants will undergo assessments including monitoring for adverse events, toxicity, and laboratory abnormalities from enrollment until about 60 days after the last dose. Pharmacokinetic measures such as maximum concentration Cmax, time to maximum concentration Tmax, and area under the curve AUC will also be evaluated. The total involvement includes regular evaluations to track safety, drug behavior in the body, and immune responses to AV-380.

Researchers are evaluating the long-term efficacy and safety of mirikizumab in children and adolescents with moderate-to-severe ulcerative colitis UC or Crohns disease CD. This Phase 3, open-label, multicenter study aims to understand how well mirikizumab works over an extended period, lasting about 172 weeks with up to 44 visits. The study is sponsored by Eli Lilly and Company and includes participants aged 2 to 19 years who have previously been treated with mirikizumab in earlier studies. Participants receive mirikizumab administered subcutaneously under the skin, with dosing based on their weight. There are multiple doses, numbered Dose 1 through Dose 6, with an additional intravenous rescue dose available if a participant loses response to the treatment. The study follows an open-label design without randomization or masking. Throughout the study, participants undergo regular assessments including clinical remission and response measured by the Modified Mayo Score for UC and the Pediatric Crohns Disease Activity Index for CD at Week 52. Other outcomes include endoscopic remission and response, corticosteroid-free remission, and changes in inflammatory markers. Safety is monitored continuously, and additional treatment may be offered during a continued access period. The total participation time can last over three years, with extensive follow-up visits and evaluations.

Researchers are evaluating a new digital health tool called Prioritize Personalize Prescribe EXercise P3-EX designed to help physicians prescribe personalized exercise plans to adults with cardiovascular disease CVD risk factors such as obesity, hypertension, dyslipidemia, and diabetes. This pilot randomized controlled trial aims to test the usability and satisfaction of P3-EX compared to a standard exercise prescription method ACSM Physical Activity Vital Sign among physicians and their patients. The study addresses barriers physicians face in prescribing exercise, including lack of time, training, and tools. Physicians recruited for the study will each recruit two patients with CVD risk factors. One patient receives a personalized exercise prescription using P3-EX, and the other receives a generic exercise program based on ACSM guidelines, delivered in a random crossover design. Patients will follow their assigned exercise plans unsupervised for 12 weeks with virtual weekly support from graduate research assistants. The P3-EX tool assesses cardiovascular risk factors, prioritizes the greatest risk, and creates a tailored Frequency, Intensity, Time, and Type FITT exercise prescription. Patients will record their exercise activities in a diary and receive weekly progress reports and guidance. Participants will attend several in-person visits for assessments including cardiovascular risk factors, physical activity levels measured by accelerometry, and blood tests. Physicians and patients will rate the feasibility and acceptability of each prescription method shortly after delivery. Patient exercise adherence and changes in cardiovascular health and physical activity will be monitored over 12 weeks. The study includes virtual visits for guidance and ends with follow-up assessments to evaluate patient satisfaction and health outcomes. The total participation time for patients covers baseline and post-intervention visits plus the 12-week exercise period.

Researchers are evaluating real-world patient characteristics, treatment methods, and long-term outcomes in people with symptomatic obstructive hypertrophic cardiomyopathy HCM in the United States and Europe. The study includes patients receiving mavacamten, other treatments, or no treatment due to intolerance or treatment failure. The US sub-study focuses on safety of mavacamten, while the European sub-study assesses both safety and effectiveness of mavacamten in everyday care. Participants may receive mavacamten or standard treatments like beta blockers, non-dihydropyridine calcium channel blockers, or disopyramide as prescribed by their doctors. The study observes these groups over time in routine clinical settings without altering their care. The study includes two main groups based on treatment type and monitors outcomes up to five years. Participants undergo evaluations including echocardiograms, heart function assessments using New York Heart Association NYHA class, left ventricular outflow tract gradient measurements, and patient-reported health questionnaires. Researchers also track heart failure events, arrhythmias, major cardiovascular events, hospitalizations, mortality, and biomarkers like NT-proBNP and cardiac troponin. Follow-up varies by region, lasting up to 18 months in Europe and up to 5 years in the United States.

Researchers are following participants with pediatric-onset hypophosphatasia HPP, a rare bone disease that begins in childhood, to understand how the treatment asfotase alfa works over time. This observational sub-study will track patients at various sites in the United States and possibly other countries for at least five years, focusing on how the body responds to the treatment and any immune-related issues that may affect its effectiveness. All participants will receive asfotase alfa given under standard care, typically as subcutaneous injections. Younger children under 2 years old are recommended to have clinic visits about every three months until they turn two, then about every six months afterward. The study monitors biochemical, clinical, imaging if needed, and quality of life outcomes related to HPP to understand the long-term effects of treatment. Participants will be regularly evaluated over a minimum five-year period, including assessments by their treating physicians to detect any loss of treatment effectiveness or serious immune-related side effects. Data collection will include clinical exams, laboratory tests, functional assessments, and quality of life questionnaires. The study aims to gather detailed information about treatment outcomes and safety in real-world settings over time.

Researchers are evaluating the effectiveness, safety, and tolerability of oral icotrokinra in treating adults and adolescents with moderately to severely active ulcerative colitis UC, a chronic condition where the large intestine lining becomes inflamed and develops ulcers. This Phase 3 clinical trial aims to compare icotrokinra with a placebo to better understand its impact on UC symptoms and remission rates. Participants will be divided into study groups receiving either icotrokinra or a placebo orally each day starting from Week 0 of the induction phase. After 12 weeks, responses will be assessed and participants who respond to icotrokinra or placebo enter a maintenance phase lasting up to Week 40. Adolescents receive open-label icotrokinra throughout the study, with an option for a long-term extension after completing the maintenance phase. During the trial, participants will undergo regular evaluations including clinical response, endoscopic assessments, and symptom monitoring at key points such as Weeks 12 and 40. Researchers will track remission rates, symptom improvements, quality of life, and safety outcomes. The study involves both double-blind and open-label phases and continues until January 2032, with close monitoring to understand how participants respond over time.

Researchers are evaluating azetukalner as a treatment for adults diagnosed with Moderate-to-Severe Major Depressive Disorder MDD. This Phase 3, randomized, double-blind, placebo-controlled study aims to assess the clinical effectiveness, safety, and tolerability of azetukalner when used alone in adults aged 18 to 74 years who are currently experiencing a major depressive episode. The study is sponsored by Xenon Pharmaceuticals Inc. and focuses on improving depressive symptoms over a six-week period. Participants will be randomly assigned to receive either azetukalner 20 mg or a placebo once daily, taken orally with food, preferably with the evening meal. Treatment lasts for six weeks, during which the effects of the medication will be closely monitored. The study uses a quadruple-blind design, meaning that participants, care providers, investigators, and outcome assessors will not know which treatment is given to ensure unbiased results. During the study, participants will undergo regular assessments including the Hamilton Depression Rating Scale HAMD-17 to measure changes in depression severity from baseline to Week 6, along with other scales like the Snaith-Hamilton Pleasure Scale SHAPS and Clinical Global Impression of Severity CGI-S. Safety and tolerability will be monitored from about four weeks before treatment through eight weeks after the final dose. The total participation duration covers treatment and follow-up to evaluate both short-term effects and safety outcomes.

This research aims to understand how blood cell growth patterns called therapy-related clonal hematopoiesis t-CH are linked to heart health or cardiovascular disease in patients who were treated for classical Hodgkin lymphoma during childhood or adolescence. It focuses on patients who received anthracycline chemotherapy and explores how these blood cell changes might predict future heart problems. The study is observational and seeks to identify patients at higher risk so they can be monitored more closely for early detection and prevention of heart complications. Participants undergo several procedures including blood sample collection, surveys, and cardiac magnetic resonance imaging MRI. Their medical records are also reviewed, and archived blood samples may be collected if available. The study compares the presence of t-CH mutations in patients with and without signs of cardiovascular disease and evaluates various factors like radiation exposure, age, sex, and medication use to understand their impact on t-CH and heart health. During the study, participants provide blood samples and complete surveys while undergoing cardiac MRI without sedation. Researchers analyze these data along with medical records to assess blood cell mutations and heart function. The main outcome measured is the presence of therapy-related clonal hematopoiesis linked to cardiovascular disease within one year. Secondary evaluations look at changes over time and associations with clinical risk factors. The study helps monitor heart health risks after lymphoma treatment and runs until 2028.

Researchers are evaluating a personalized approach to chemoradiation therapy compared to standard chemoradiation therapy in people with HPV-positive throat cancer. This study aims to find out if using a lower dose of radiation with standard chemotherapy is as effective as the standard radiation dose combined with chemotherapy. The study also looks at whether the lower radiation dose causes fewer side effects and how each treatment affects patients quality of life, measured through questionnaires. Participants will be randomly assigned to one of two treatment groups. One group receives personalized chemoradiation therapy where radiation dose is adjusted based on tumor hypoxia detected by a special FMISO-PET scan hypoxia-negative patients receive 30 Gy of radiation, while hypoxia-positive patients receive 70 Gy. The other group receives the standard chemoradiation therapy of 70 Gy radiation regardless of hypoxia status. Both groups receive concurrent chemotherapy as per guidelines. After treatment, a PETCT scan is done about four months later to check for persistent disease, and further standard care is provided as needed. During the study, participants will undergo the FMISO-PET scan, routine chemotherapy and radiation treatments, and quality of life assessments using specific questionnaires. Researchers will monitor overall survival over two years as the primary outcome. Safety and treatment effects will be evaluated through follow-up scans and clinical assessments. Participation involves regular visits for scans, treatments, and questionnaires, with the study lasting at least two years to assess outcomes.