Herston

Researchers are conducting a Phase 1, open-label study to explore the pharmacokinetic profiles, safety, and tolerability of two investigational long-acting injectable forms of naltrexone, IVL3004 and IVL4002, compared to Vivitrol® (a marketed naltrexone long-acting injectable) in healthy male adults. The study targets men aged 18 to 55 years who are generally healthy and non-smokers or occasional smokers. The purpose is to understand how these drugs behave in the body, including how they are absorbed and processed over time. The study involves administering single ascending doses of IVL3004, IVL4002, and Vivitrol® in a fixed sequence to participants. These long-acting injections will be given either subcutaneously in the abdomen or intramuscularly in the ventral gluteal area. Participants will receive these injections under controlled conditions to evaluate the drug levels over specific periods and assess safety and tolerability. Participants will be closely monitored through physical exams, laboratory tests, and vital sign checks before and after dosing up to Day 57. Key measurements include drug concentration over time (pharmacokinetic parameters such as AUC and Cmax). Safety assessments will also be conducted, including monitoring for adverse reactions. The study requires participants to abstain from smoking during confinement and avoid donating sperm for 90 days after dosing. Overall participation includes screening, dosing, and follow-up visits extending up to 57 days after the last dose.

Researchers are evaluating the safety and effectiveness of the WiSE CRT System combined with an intracardiac pacemaker to achieve a totally leadless cardiac resynchronization therapy (CRT) for patients with heart failure. This is a single-arm, prospective, multicenter observational study focused on patients who meet specific guidelines for CRT implantation, including those with certain heart rhythm and heart function characteristics. The study aims to provide a leadless solution that may benefit patients with anatomical or infection-related concerns for traditional devices. Participants will receive the WiSE CRT System, an implantable device that provides left ventricular pacing stimulation, working together with an existing system that provides right ventricular pacing. Together, these devices deliver biventricular pacing to improve heart function. The study involves patients receiving either a new totally leadless CRT implant or an upgrade from a chronic intracardiac pacemaker to CRT. Treatment is delivered through device implantation, with follow-up visits scheduled to monitor outcomes. During the study, participants will be monitored for device- and procedure-related complications at 1 month and 6 months after implantation. Researchers will also assess biventricular capture using a 12-lead ECG at these same time points. Patients will provide consent and undergo assessments according to study protocols, with safety and effectiveness data collected throughout the follow-up period. The total duration and schedule of follow-up visits are designed to ensure careful observation of the devices' performance and patient health.

Researchers are evaluating the safety and effectiveness of three different doses of MORF-057 in adults with moderately to severely active Crohn's disease (CD). This Phase 2 study is randomized, double-blind, placebo-controlled, and conducted at multiple centers. It aims to compare MORF-057 to placebo to see how well it works in reducing disease activity and symptoms in this patient population. Participants will first go through a 14-week induction period where they receive one of three doses of MORF-057 or a matching placebo, all given orally. After this, all participants will enter a 38-week maintenance phase where they receive open-label MORF-057. Those who complete these 52 weeks of treatment may continue in a 52-week long-term extension to further monitor treatment effects and safety. Throughout the study, participants will have evaluations to assess their response to treatment using endoscopic scoring at Week 14. Researchers will monitor safety, symptom changes, and disease activity over the full treatment and extension periods. Study visits will include assessments, questionnaires, and clinical monitoring to track participants' health and treatment adherence over time.

Researchers are conducting a phase 3 open-label, randomized, controlled, multicenter study to compare petosemtamab with investigator's choice monotherapy in patients with head and neck squamous cell carcinoma (HNSCC) who have incurable metastatic or recurrent disease. This study focuses on patients with progressive disease after anti-PD-1 therapy and platinum-containing therapy and aims to evaluate the treatments as second- or third-line options. Participants will receive either petosemtamab or one of the investigator's choice monotherapies, including cetuximab, methotrexate, or docetaxel. The study involves treatment administration under controlled conditions with monitoring for efficacy and safety. The goal is to assess the treatments over time with a focus on response rates and overall survival. During the study, participants will undergo regular assessments including radiologic imaging to measure tumor response, and evaluations of overall survival up to approximately three years. The primary outcomes include objective response rate assessed by blinded independent central review and overall survival. Researchers will monitor patient health, side effects, and treatment effectiveness throughout the study duration.

Researchers are evaluating the safety, tolerability, and effectiveness of LP352 in reducing seizures among children and adults diagnosed with Dravet Syndrome (DS). This phase 3, double-blind, randomized, placebo-controlled study aims to compare LP352 with a placebo to better understand its impact on seizure frequency in this population. The study involves participants aged 2 to 65 years and addresses the challenges patients with DS face due to various seizure types and treatment responses. Participants will receive either LP352 or a matching placebo, administered orally or through a feeding tube (G-tube or PEG tube). The study includes several phases: an initial screening period, followed by a titration period to adjust doses, then a maintenance period where treatment continues, and finally a taper period to gradually reduce treatment before a follow-up phase. The entire study duration is approximately 24 months. During the study, participants will be monitored for changes in the frequency of countable motor seizures compared to their baseline seizure activity over up to 15 weeks. They will be required to complete diaries throughout the study to track seizures and treatment adherence. Safety and tolerability will also be assessed throughout all study phases. The researchers will collect data on seizure counts and monitor participants' health to evaluate LP352's effects comprehensively.

Researchers are evaluating different treatment strategies for patients hospitalized with Gram-negative bloodstream infections (GN BSIs) through the BALANCE+ trial. This adaptive platform trial uses an open-label, pragmatic design embedded in routine care to address important questions in managing GN BSIs, including antibiotic treatment duration, antibiotic de-escalation, oral antibiotic options, central line management, specific pathogen treatment, and follow-up blood cultures. The study builds on previous research and aims to improve patient outcomes and reduce antimicrobial resistance, a growing global health concern. The trial includes multiple treatment comparisons, such as de-escalation versus no de-escalation of antibiotics, oral beta-lactams versus non-beta-lactams, central vascular catheter retention versus replacement, cephalosporin versus carbapenem for low-risk AmpC organisms, and routine follow-up blood cultures versus no routine follow-up. Treatments are tailored based on blood culture results and clinical decisions, with specific protocols for antibiotic switching and catheter management. The trial uses Bayesian methods with interim analyses after every 1000 patients initially, then every 200 patients, and stops domains based on predefined criteria or sample sizes. Participants are patients admitted to hospitals with confirmed Gram-negative bacteremia who meet eligibility criteria for each domain. Assessments include monitoring for death, reinfection, readmission, and new antimicrobial resistance over 90 days, measured by the Desirability of Outcome Ranking (DOOR) scale. The trial incorporates detailed inclusion and exclusion criteria and collects data through routine clinical care, ensuring ongoing evaluation of treatment effectiveness and safety throughout the study period.

Researchers are conducting a phase II randomized, placebo-controlled trial to study the effects of oral N-Acetylcysteine (NAC) in adults who carry the Huntington disease gene expansion but do not yet show clear motor symptoms. The study aims to evaluate clinical and brain imaging outcomes over a period of up to three years to better understand NAC's potential impact on disease progression in this premanifest stage. Participants are randomly assigned to receive either 1 gram of clinical grade NAC capsules or matching placebo capsules, taken orally twice daily. The trial includes detailed monitoring through clinical assessments and magnetic resonance imaging (MRI) scans to track changes in brain structure, particularly focusing on the rate of caudate atrophy. The study also measures the rate at which participants develop motor symptoms indicative of Huntington disease over the three-year period. Throughout the study, participants will undergo regular clinical evaluations and MRI scans to monitor neurological changes and motor function. Researchers will collect data on caudate atrophy rates and motor symptom development to assess treatment effects. Safety and tolerability are closely observed, with ongoing assessments to ensure participant well-being during the study's duration of up to three years.

Researchers are evaluating efruxifermin (EFX) in adults aged 18 to 80 who have compensated cirrhosis caused by nonalcoholic steatohepatitis (NASH) or metabolic dysfunction-associated steatohepatitis (MASH). This Phase 3, randomized, double-blind, placebo-controlled study aims to assess the safety and effectiveness of EFX in improving liver health and delaying disease progression in this population. The study focuses on subjects with advanced liver fibrosis (stage 4) but without liver decompensation. Participants are randomly assigned to receive either efruxifermin or a placebo, both administered by subcutaneous injection. The study includes two cohorts: Cohort 1 requires biopsy confirmation of liver fibrosis and specific metabolic features, while Cohort 2 allows biopsy or non-invasive diagnosis. Treatment and observation continue over an extended period to evaluate changes in liver fibrosis and clinical events. During the study, researchers will monitor the time until significant clinical events such as disease progression or liver decompensation occur, with a follow-up of up to five years. For Cohort 1, the proportion of participants showing improvement in fibrosis without worsening steatohepatitis will be assessed at 96 weeks. Participants will undergo regular evaluations including clinical assessments and laboratory tests to track liver function and safety throughout the study period.

Researchers are evaluating the persistence of the immune response and the safety and immune response after revaccination with the adjuvanted RSVPreF3 vaccine in adults aged 18 and older who have received lung or kidney transplants. This phase 2b extension study focuses on individuals who previously received one or two doses of this vaccine in an earlier study and are now receiving an additional dose to assess continued protection and safety. Participants who received either one or two doses of the adjuvanted RSVPreF3 vaccine in the prior RSV OA=ADJ-023 study will receive a single intramuscular dose of the same vaccine at the start of this study (Day 1). They will be grouped based on their initial dosing for immune response analyses but combined for safety and demographic evaluations. Throughout the study, participants will have visits on Day 1, Day 31, and Day 180 to measure immune responses against RSV-A and RSV-B through neutralizing antibody levels. Safety and immune system responses will be monitored, including detailed evaluations of antibody levels at each visit to understand vaccine persistence and revaccination effects over time.

This research aims to evaluate the effectiveness and safety of two different dose schedules of pegozafermin compared to a placebo in adults with metabolic dysfunction-associated steatohepatitis (MASH) who have liver fibrosis at stage F2 or F3. This phase 3 study focuses on improving liver fibrosis and steatohepatitis in this patient group, which involves chronic liver disease associated with metabolic dysfunction. Participants will receive either pegozafermin or a placebo through subcutaneous injections. The study compares two doses of pegozafermin to assess their impact on liver fibrosis and steatohepatitis. The treatment period lasts up to 52 weeks, with outcomes measured at this time point. During the study, participants will be monitored for improvements in liver fibrosis and resolution of steatohepatitis without worsening fibrosis by week 52. Researchers will also track the time until any disease progression occurs, up to 5 years. Throughout the trial, safety and efficacy will be carefully assessed through clinical evaluations and laboratory tests to ensure participant well-being.