Richmond

Researchers are conducting a phase 4, double-blind, randomized, placebo-controlled trial to evaluate the effectiveness of n-acetylcysteine (NAC) in improving treatment outcomes for adults with Alcohol Use Disorder (AUD) in Australia. The study addresses the urgent need for new, evidence-based treatments in AUD, as current medications have limited success and do not consider individual differences such as genetics and coexisting clinical conditions. This trial builds on previous pilot research to test whether NAC can help reduce heavy drinking more effectively than placebo. Participants will receive either 2400 mg per day of NAC or a matched placebo for 12 weeks. The study will include 280 adults aged 18 to 70 years who meet AUD criteria and have a history of heavy drinking. The trial uses a double-blind design, so neither the participants nor the researchers know who receives NAC or placebo during the treatment period. During the study, participants will be closely monitored through research interviews and assessments to evaluate changes in heavy drinking days over 24 weeks. Participants must have stable housing and sufficient cognition and English skills to provide informed consent and complete study procedures. Safety and tolerability of NAC will also be assessed, alongside adherence to treatment and any side effects. The primary outcome is the number of heavy drinking days measured over 24 weeks.

Researchers are evaluating ziltivekimab as a treatment for people living with heart failure and inflammation. This Phase 3 study compares ziltivekimab to a placebo in participants with heart failure who have mild to preserved ejection fraction and systemic inflammation. The study aims to assess the effect of ziltivekimab on cardiovascular death, heart failure hospitalization, or urgent heart failure visits over a period of up to 4 years. Participants will receive monthly injections of either ziltivekimab or a placebo using a pre-filled syringe or a pen-injector. The study medication is administered subcutaneously once a month for up to 4 years. The trial includes up to 20 clinic visits during which participants will be monitored and assessed. During the study, participants will use a study app on their phone to record all injections and complete questionnaires. Researchers will monitor participants for key outcomes like cardiovascular events and heart failure episodes from the time of randomization until the end of the study. Safety and health status will be regularly evaluated throughout the study period, which may last up to 48 months.

Researchers are evaluating the effectiveness of anitocabtagene autoleucel compared to standard of care therapy in adults with relapsed or refractory multiple myeloma who have previously received one to three treatments, including an anti-CD38 monoclonal antibody and an immunomodulatory drug. The study is a Phase 3, randomized, open-label trial aiming to assess how well anitocabtagene autoleucel works versus existing therapies in this patient group. Participants will receive either a single infusion of anitocabtagene autoleucel, which is a CAR+ transduced autologous T cell therapy, or one of several standard of care treatments. The standard treatments include combinations involving drugs such as pomalidomide, bortezomib, dexamethasone, daratumumab, carfilzomib, cyclophosphamide, and fludarabine, administered either orally or intravenously/subcutaneously. After the treatment period, those receiving anitocabtagene autoleucel will enter a follow-up phase and then transition to a long-term follow-up study lasting up to 15 years. During the study, participants will be monitored for progression-free survival for up to four years and for minimal residual disease complete response rate at nine months. Researchers will assess disease progression, treatment safety, and other health markers. Follow-up includes regular evaluations to track the participant's response and overall health status, with continued long-term monitoring planned for those treated with anitocabtagene autoleucel.

Researchers are evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of DR-01 in adults with large granular lymphocytic leukemia or various types of cytotoxic lymphomas. This is a first-in-human, multicenter Phase 1/2 study aiming to find appropriate dosing and to assess how well DR-01 works in these populations. DR-01 is a non-fucosylated human immunoglobulin G1 monoclonal antibody given to participants. The study includes multiple parts: Part A focuses on safety and finding the best dose by monitoring adverse events, dose-limiting toxicities, and drug effects for up to six months. Part B evaluates overall response rates, measuring how many participants achieve complete or partial response over up to 24 months. Participants will undergo various assessments including monitoring for adverse events using CTCAE criteria, pharmacokinetic and pharmacodynamic tests, and disease-specific response evaluations. Tissue samples or biopsies may be collected if needed. Safety follow-up can last up to 25 months, with ongoing evaluation of treatment effects and side effects. The study requires participants to meet specific disease and health criteria and to comply with study procedures throughout the treatment and observation periods.

Researchers are investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral Nuvisertib (TP-3654) in patients with intermediate or high-risk primary or secondary myelofibrosis. This Phase 1/2 open-label, multicenter, dose-escalation trial includes patients who have previously been treated with JAK inhibitors or are ineligible for them. The study aims to assess how the drug behaves in the body and its safety profile in this patient group. The study consists of three arms: one enrolling patients treated with JAK inhibitors who are intolerant or resistant; a second arm including patients on a stable dose of ruxolitinib but with suboptimal or lost response; and a third arm with patients previously treated with a JAK inhibitor other than momelotinib. Participants receive oral Nuvisertib alone or in combination with ruxolitinib or momelotinib. Treatment dosing and schedules follow a dose-escalation and expansion design specific to each arm. Participants undergo assessments to monitor dose-limiting toxicities within 28 days and treatment-emergent adverse events throughout the study. Researchers also evaluate preliminary activity by measuring spleen volume reduction. Regular laboratory tests, imaging scans, and symptom questionnaires are used to track safety and effectiveness. The total study duration includes screening, treatment, and follow-up periods to ensure comprehensive monitoring of patient outcomes.

Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and change in disease activity of ABBV-453 in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed. ABBV-453 is an investigational drug being developed for the treatment of R/R MM. In Substudy 1 there will be a dose escalation phase where participants will receive various doses of ABBV-453 in combination with daratumumab + dexamethasone, to determine the best dose of ABBV-453. This will be followed by a dose expansion and selection phase where participants will receive 1 of 2 doses of ABBV-453 in combination with daratumumab + dexamethasone, or daratumumab + dexamethasone + pomalidomide (only during the expansion phase). In Substudy 2, there will be a dose escalation phase where participants will receive various doses of ABBV-453 alone. Approximately 130 adult participants with R/R MM will be enrolled in the study in approximately 40 sites worldwide. In Substudy 1 escalation phase, participants will receive oral ABBV-453 tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive oral ABBV-453 tablets in combination with SC daratumumab injections + oral dexamethasone tablets or daratumumab injections + oral pomalidomide + oral dexamethasone tablets. In Substudy 2, Japanese participants will receive oral ABBV-453 tablets. The total study duration is approximately 4.5 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution. The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.

Researchers are evaluating the effectiveness of glofitamab given alone compared to an investigator's choice of treatment in patients with relapsed or refractory mantle cell lymphoma (MCL). This Phase III, open-label study focuses on patients whose disease has progressed after previous therapies, including BTK inhibitors. The goal is to see which treatment better controls the lymphoma and prolongs the time before the disease worsens or leads to death. Participants are assigned to receive either glofitamab alone or one of two combination therapies selected by the investigator: rituximab plus bendamustine or lenalidomide with rituximab. All patients receive two pretreatments of intravenous obinutuzumab starting on Cycle 1 Day 1. Those in the glofitamab group begin intravenous glofitamab on Cycle 1 Day 8 and continue for 12 cycles, each lasting 21 days. Patients receiving the combination therapies get intravenous rituximab every 28 days, with bendamustine given on Days 1 and 2 of each 28-day cycle for six cycles, or oral lenalidomide daily on Days 1-21 of each 28-day cycle until disease progression. Tocilizumab is available as needed to manage any cytokine release syndrome events. Throughout the study, participants undergo regular assessments to track disease progression, including imaging and laboratory tests. The primary measure is progression-free survival, defined as the time from randomization until disease worsening or death, monitored for up to about 24 months. Safety is closely observed, and patients are evaluated for treatment response and adverse effects. The study involves ongoing monitoring during treatment cycles and follow-up periods to understand the impact of the therapies on the lymphoma and patient health.

Researchers are evaluating the safety and tolerability of elranatamab combined with iberdomide in patients with relapsed or refractory multiple myeloma, a cancer that starts in plasma cells. This Phase 1 study has two parts: the first focuses on safety and tolerability, while the second determines the appropriate dose of this combination treatment. Relapsed means the disease has returned after improvement, and refractory means it does not respond to treatment. All participants receive elranatamab as a subcutaneous injection and take iberdomide orally once daily for 21 days in a 28-day cycle. Treatment continues until the disease worsens, unacceptable side effects occur, or the participant chooses to stop. The study drugs include elranatamab, a BCMA-CD3 bispecific antibody, and iberdomide, a cereblon-modulating agent. Participants will be closely monitored throughout the study with evaluations of side effects and treatment responses. Safety is assessed by tracking dose-limiting toxicities during the first treatment cycle and adverse events for up to 90 days after the last dose. The overall goal is to understand if this treatment combination is safe and tolerable for patients with multiple myeloma.

Researchers are evaluating the combination of Elranatamab, Daratumumab, and Lenalidomide compared to Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone in people with newly diagnosed multiple myeloma who are not eligible for transplant. Elranatamab is a bispecific antibody that targets T-cells and multiple myeloma cells to trigger targeted immune cell killing. The study has two parts: Part 1 focuses on safety, tolerability, and optimal dosing of Elranatamab combinations, while Part 2 compares clinical benefits including minimal residual disease negative complete response rates and progression-free survival between the two treatment regimens. In Part 1, participants receive Elranatamab combined with Daratumumab and Lenalidomide or with Lenalidomide alone to determine safe dose levels. This phase includes non-randomized and randomized cohorts. In Part 2, participants are randomly assigned to receive either the combination of Elranatamab, Daratumumab, and Lenalidomide or the combination of Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone. Treatment schedules and doses are managed according to study protocols to evaluate efficacy and safety. Participants undergo regular assessments including monitoring for dose-limiting toxicities in Part 1 from the first dose through 28 days, and in Part 2, evaluation of progression-free survival up to 97 months and minimal residual disease negative complete response at 12 months after randomization. Safety and tolerability are closely monitored throughout the study, with ongoing follow-up to assess treatment effects and outcomes over time.

Researchers are evaluating the study medicine elranatamab alone and in combination with daratumumab for people with relapsed or refractory multiple myeloma who have received prior treatments including lenalidomide and a proteasome inhibitor. The study aims to compare elranatamab to a combination therapy of daratumumab, pomalidomide, and dexamethasone, while also assessing the safety and activity of elranatamab with daratumumab. This is an open-label, phase 3 randomized trial involving multiple centers. The study includes three parts. Part 1 evaluates the safety and activity of different doses of elranatamab combined with daratumumab. In Part 2, participants are randomly assigned to receive either elranatamab alone, elranatamab with daratumumab, or the combination of daratumumab, pomalidomide, and dexamethasone. Part 3 investigates the effect of increased infection protection measures in participants treated with elranatamab alone or with daratumumab. All drugs are given by either subcutaneous injection or orally depending on the medication. Participants will receive study treatment until their disease worsens, unacceptable side effects occur, or they decide to stop. Researchers will monitor safety by tracking dose limiting toxicities during the first 42 days after starting elranatamab and treatment-emergent adverse events during the first 84 days. Progression-free survival will be assessed up to 51 months after randomization. Throughout the study, participants will undergo regular assessments to evaluate treatment safety and effectiveness.