Hartford

This study consists of 2 week screening period in which subjects who have consented will be evaluated for eligibility per protocol requirements. During this 2 week screening period subjects will be given access to ediary in which they will be required to self report symptoms of IBS-C daily. Information in ediary will also be used to determine eligibility prior to enrollment. During the 4 week RTP (Randomized treatment period), subjects will be randomized in in a ratio of 5:1 to receive tenapanor or matching placebo for 4 weeks. During the RTP, patients will continue recording daily assessments in the eDiary system as instructed and compliance with eDiary entries will be monitored. Patients will return for study visit every weeks (Visits 3-6) and will undergo safety assessments as per the protocol. At the end of this 4 week period, subjects will complete 2 week treatment free follow-up period and safety assessments per protocol will be conducted at the end of this 2 week period. The study plans to enroll up to 6 cohorts of eligible patients sequentially, starting from Cohort 1 with 12 patients randomized in to receive tenapanor 2 mg BID or matching placebo for 4 weeks. Subsequent cohorts will assess increasing tenapanor doses, following a dose escalation order. The study will proceed to the next dosing cohort if the current cohort completes the 4-week RTP and does not meet any of the dose escalation stopping criteria pre-specified in the protocol.

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.

Researchers are conducting a Phase 1B open-label dose escalation study to evaluate AV-380 in cancer patients experiencing cachexia, a condition involving severe weight loss and muscle wasting. AV-380 is a monoclonal antibody designed to bind to the growth differentiation factor 15 (GDF-15), a protein involved in cancer-related cachexia. The study aims to assess the safety, how the drug moves through and affects the body (pharmacokinetics and pharmacodynamics), and its potential immune response effects in patients actively receiving standard cancer treatments. Participants will receive increasing doses of AV-380 alongside their standard of care chemotherapy to determine appropriate dosing and monitor for any adverse effects. AV-380, a biological therapy, targets GDF-15 to potentially impact cachexia symptoms. The study involves treatment periods lasting up to four months, with careful observation during drug administration and follow-up visits. Throughout the study, participants will be closely monitored for adverse events, toxicity, and laboratory abnormalities from the time of enrollment through approximately 60 days after the last dose. Safety assessments and laboratory tests will be regularly conducted to evaluate the body's response to AV-380. The study involves active cancer patients with cachexia, with various evaluations to understand the drug's safety profile and effects over the study duration.

This research investigates the long-term effects of mirikizumab in children and adolescents aged 2 to 19 years with moderate-to-severe ulcerative colitis or Crohn's disease. The study is designed as a Phase 3, multicenter, open-label extension trial aiming to assess the ongoing safety and efficacy of this treatment in pediatric participants. It includes those who have completed previous related studies and are expected to benefit from continued mirikizumab treatment. Participants will receive mirikizumab either by subcutaneous injection or intravenous infusion as part of this extended treatment. The study may last approximately 172 weeks and involve up to 44 visits over this period. There is also a possibility for participants to continue receiving treatment through a Continued Access Period after the main study. Throughout the study, participants will be regularly monitored with clinical assessments to determine remission status using the Modified Mayo Score for ulcerative colitis and the Pediatric Crohn's Disease Activity Index for Crohn's disease at week 52. Safety and efficacy will be closely followed, including the evaluation of any adverse events or changes in disease activity, ensuring comprehensive long-term observation.

Researchers are evaluating the feasibility and preliminary effectiveness of a new digital health tool called Prioritize Personalize Prescribe EXercise (P3-EX) for physicians to use when prescribing exercise to patients with cardiovascular disease (CVD) risk factors such as obesity, hypertension, dyslipidemia, and diabetes. This pilot randomized controlled trial will involve 24 physicians and 48 patients, aiming to compare P3-EX with the American College of Sports Medicine Physical Activity Vital Sign (ACSM-PAVS) method. The study addresses the challenge that many patients with CVD risk factors do not receive exercise advice due to barriers faced by physicians, including lack of time, training, and tools. Physicians will each prescribe exercise to two patients, one receiving the P3-EX exercise prescription and the other receiving the ACSM-PAVS prescription, in a randomized crossover design. Patients will follow a 12-week unsupervised exercise program with virtual weekly support from University of Connecticut Graduate Research Assistants. Participants will receive a detailed exercise information packet, record their daily exercise in a diary, and attend two virtual guidance visits during the intervention. Weekly progressive exercise goals and summary reports will be emailed to patients to support adherence. Participants will attend multiple in-person visits for assessments before and after the exercise program, including cardiovascular risk factor measurements, physical activity monitoring using accelerometers, blood tests, and questionnaires on exercise adherence and satisfaction. Physicians and patients will also complete usability and satisfaction surveys within 48 hours after receiving the exercise prescriptions. The study will monitor exercise adherence through diaries and virtual oversight over the 12 weeks, aiming to inform the feasibility and user satisfaction of P3-EX and explore its potential to improve cardiovascular health and physical activity levels.

Researchers are studying patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the United States and Europe to understand their characteristics, treatment patterns, and outcomes over time. The study focuses on individuals who are receiving mavacamten, other treatments for obstructive HCM, or no treatment due to intolerance or failure of prior therapies. The research includes a United States sub-study to evaluate mavacamten's safety and a European sub-study to assess both its effectiveness and safety in real-world settings. Participants may receive mavacamten according to its product label or other symptomatic therapies such as beta-blockers, non-dihydropyridine calcium channel blockers, or disopyramide based on standard care. The study includes those starting mavacamten, currently on other treatments, or untreated due to intolerance or failure of prior therapy. Treatment is observed during routine clinical care without altering prescribed therapy. Data collection occurs over several years to monitor long-term outcomes. During the study, participants will be regularly assessed for heart function and symptoms, including measuring the left ventricular outflow tract gradient and monitoring the incidence of new or worsening heart failure up to five years. Researchers will gather information on patient health, treatment safety, and heart function changes through echocardiography and symptom evaluations. The study allows for long-term observation to better understand real-world treatment effects and outcomes in obstructive HCM patients.

Researchers are conducting a prospective observational sub-study involving participants with pediatric-onset hypophosphatasia (HPP), which includes perinatal/infantile or juvenile onset forms. The study will follow participants of any age for at least 5 years at sites in the United States and potentially one or two other countries. The focus is on describing the potential risk of immune-mediated loss of the pharmacological effect of asfotase alfa treatment in these individuals. All participants will receive asfotase alfa by subcutaneous injection according to standard care. For children under 2 years old, clinic visits are recommended approximately every 3 months until age 2, then every 6 months thereafter. Participants are expected to be followed for up to 5 years as possible. Treatment may be newly started, resumed, or ongoing at enrollment based on the physician's decision. During the study, participants will have their alkaline phosphatase (ALP) activity and ALPL gene mutation status documented if not already done. The study will monitor for immune-mediated loss of treatment effectiveness and serious immune-related adverse events over up to 5 years. Participants or their caregivers will provide informed consent and complete questionnaires in their local language. The study excludes those currently enrolled in an Alexion-sponsored interventional clinical study but allows previous trial participants who have completed their involvement to join this sub-study.

Researchers are evaluating how well oral icotrokinra works, its safety, and how well patients tolerate it in adults and adolescents with moderately to severely active ulcerative colitis, a chronic condition where the colon lining becomes inflamed and develops ulcers. This is a Phase 3 study aimed at finding effective treatments for this condition using a rigorous comparison. Participants will receive either icotrokinra tablets or placebo tablets taken by mouth. The study includes an induction phase and a maintenance phase, with adults participating in a randomized, double-blind, placebo-controlled design, while adolescents join an open-label maintenance study. Throughout the study, researchers will monitor clinical remission rates at 12 weeks during induction and at 40 weeks during maintenance. Participants will undergo assessments including endoscopic evaluations and pregnancy tests for females of childbearing potential. Safety and tolerability will be closely observed, with the total study duration covering both induction and maintenance periods.

Researchers are evaluating the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adults diagnosed with moderate-to-severe Major Depressive Disorder (MDD). This Phase 3, multicenter, randomized, double-blind, placebo-controlled study focuses on participants aged 18 to 74 who have experienced their first major depressive episode before age 50. The study aims to compare azetukalner with placebo in treating MDD over a 6-week period. Participants will receive either azetukalner 20 mg or placebo orally once a day with food, preferably with the evening meal, for 6 weeks. The treatment is administered as a daily oral dose, and participants are randomly assigned to one of the two groups. The study is designed to maintain blinding of treatments to both participants and researchers. During the study, participants' depression symptoms will be assessed using the Hamilton Depression Rating Scale (HAMD-17) to measure changes from baseline to Week 6. Researchers will also monitor safety and tolerability throughout the treatment period. Participants will undergo regular evaluations, and the study includes careful screening to ensure eligibility and monitor any adverse effects during the 6 weeks of treatment.

Researchers are investigating how patterns of blood cell growth called therapy-related clonal hematopoiesis (t-CH), which involve mutations linked to cardiovascular disease (CVD), relate to heart health in patients treated for classical Hodgkin Lymphoma during childhood or adolescence. The study aims to assess how common these blood cell mutations are in patients exposed to anthracycline chemotherapy and how these mutations associate with signs of heart disease detected by cardiac MRI. The research also explores whether factors such as radiation treatment, patient characteristics, and clinical risk factors influence the presence of t-CH and its impact on heart health over time. Participants undergo several procedures including blood sample collection, retrieval of archived blood samples if available, medical record review, completion of surveys, and cardiac magnetic resonance imaging (MRI) without sedation. The study compares rates of t-CH mutations and cardiovascular findings between groups with and without clinical risk factors or radiation exposure. This is an observational study where all treatment has been completed at least two years prior to enrollment. Throughout the study, researchers collect data from blood tests, MRI scans, surveys, and medical records to monitor the presence of t-CH mutations and objective signs of cardiovascular disease. The primary outcome focuses on the detection of therapy-related clonal hematopoiesis with mutations linked to heart disease over one year. Participants must be able to undergo cardiac MRI without sedation and have access to the imaging at the enrolling institution. The goal is to better understand heart health risks in Hodgkin Lymphoma survivors to enable closer monitoring and early intervention if needed.