Yamagata

Researchers are evaluating whether the drugs retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at high risk. This Phase 3 trial enrolls about 4,500 adults with MASLD identified by non-invasive tests indicating an increased likelihood of developing serious liver problems. The study aims to understand how these treatments might affect liver health over time compared to a placebo. Participants will be randomly assigned to receive either retatrutide, tirzepatide, or a placebo, all given by subcutaneous injection. The study will last approximately 224 weeks, during which participants may attend 25 to 30 clinic visits for monitoring and assessment. After the main study, eligible participants can join an optional 2-year extension where all will receive either retatrutide or tirzepatide regardless of their original group. Throughout the trial, participants’ liver function and disease progression will be closely monitored through various health assessments. Researchers will track the time to the first major adverse liver event as the main outcome. Safety and health status will be evaluated regularly during clinic visits, ensuring thorough observation over the long study period.

Researchers are evaluating the oral azacitidine formulations combined with cedazuridine (CED) tablets in patients with Myelodysplastic Syndrome (MDS) to find doses that achieve similar drug exposure levels to standard azacitidine injections. This Phase 1, multi-center, open-label trial focuses on patients diagnosed with various subtypes of MDS, including refractory anemia and chronic myelomonocytic leukemia. Treatment begins with a single oral dose of azacitidine formulations on day -3 of Cycle 1, followed by subcutaneous azacitidine injection on day 1. From day 2 to day 7 of Cycle 1, and throughout subsequent cycles, patients receive both oral azacitidine formulations and CED tablets daily for seven days per cycle. This dose-escalation study aims to assess pharmacokinetics and drug exposure over these treatment periods. Participants will undergo assessments including monitoring of drug levels to compare oral and injection forms, safety evaluations, and organ function tests. The primary outcome is the total area under the curve (AUC) ratio of azacitidine after oral administration compared with the injection, measured up to one month. Patients are expected to be followed through treatment cycles with monitoring for adverse events, survival, and treatment response during the study.

Researchers are studying bleximenib, an investigational drug taken orally, to find the best dose for treating acute leukemia and to evaluate its safety and effectiveness. In Phase 1, they aim to identify the recommended Phase 2 dose (RP2D) through a dose escalation and expansion process. Phase 2 will focus on assessing how well bleximenib works at the recommended dose in participants with relapsed or refractory acute leukemia, particularly those with specific genetic alterations in KMT2A, NPM1, or NUP98/NUP214. The study involves administering bleximenib orally and includes different participant groups based on age and disease status. Phase 1 includes pediatric participants aged 2 to less than 18 years and adults 18 years and older with relapsed or refractory acute leukemia who have limited treatment options. Phase 2 focuses on adults over 18 with relapsed or refractory acute myeloid leukemia harboring KMT2A or NPM1 mutations. The trial monitors participants for dose-limiting toxicities, adverse events, and treatment tolerability over periods lasting up to nearly five years. Participants will undergo evaluations of safety, including the number and severity of adverse events and dose-limiting toxicities during the first cycle. The effectiveness measure in Phase 2 is the rate of complete remission or remission with partial blood count recovery. Throughout the study, participants will be assessed using laboratory tests, performance status scales, and pregnancy tests as applicable. Safety monitoring and long-term follow-up will continue for up to 4 years and 9 months to fully evaluate treatment effects and tolerability.

Researchers are evaluating the safety and effectiveness of HLX22 combined with trastuzumab and chemotherapy as the first treatment for patients with HER2-positive locally advanced or metastatic adenocarcinoma of the gastric or gastroesophageal junction. This phase 2, double-blind, randomized, and multiregional study compares this combination against trastuzumab and chemotherapy with or without pembrolizumab. The study aims to measure how well the treatments work in controlling the disease and improving survival for up to five years. Participants will be randomly assigned to one of two groups. One group receives HLX22 at 15 mg/kg every three weeks along with trastuzumab, chemotherapy (XELOX regimen), and possibly a placebo for pembrolizumab. The other group receives a placebo for HLX22 plus trastuzumab, chemotherapy (XELOX), and possibly pembrolizumab every three weeks. Treatment continues until the disease worsens, unacceptable side effects occur, withdrawal of consent, or other protocol-specified reasons. Throughout the study, participants will undergo regular assessments including tumor scans reviewed by an independent committee to evaluate progression-free survival and overall survival over up to five years. Other evaluations include safety monitoring and organ function tests. The study tracks how long patients live without disease progression and overall survival, aiming to better understand the benefits and risks of HLX22 combined with current standard treatments.

Researchers are evaluating SEA-CD70, alone and combined with azacitidine, in adults with myeloid malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This phase 1, open-label study aims to find safe dosing levels, assess side effects, and explore whether these treatments work. The trial includes several parts, each focused on different patient groups and treatment combinations, including those who are relapsed, refractory, or untreated, and those unfit for standard chemotherapy. The study involves seven parts: dose-finding for SEA-CD70 alone (Part A) and with azacitidine (Part D), safety and tolerability expansions for SEA-CD70 monotherapy in MDS (Part B) and AML (Part C), and expansions for SEA-CD70 with azacitidine in untreated or relapsed/refractory MDS or MDS/AML (Parts E and F). Part G evaluates dosing and safety of SEA-CD70 with azacitidine and venetoclax in untreated AML patients unfit for standard chemotherapy. SEA-CD70 is given intravenously on days 1 and 15 of each cycle; azacitidine is administered subcutaneously or intravenously on days 1 through 7; venetoclax is taken orally daily with dose ramping. Participants will be monitored for side effects, laboratory abnormalities, and dose-limiting toxicities during and up to about two years after the last dose. Safety, tolerability, and antitumor activity will be evaluated through clinical assessments, laboratory tests, and patient monitoring throughout the study. The study duration varies by part, including dose escalation, expansion, and follow-up periods to assess long-term safety and efficacy outcomes.

Researchers are evaluating the effect of a triple therapy inhaler called BGF MDI containing budesonide, glycopyrronium, and formoterol fumarate compared with a dual therapy inhaler called GFF MDI containing glycopyrronium and formoterol fumarate in people with Chronic Obstructive Pulmonary Disease (COPD) who have a higher risk of heart and lung problems. This Phase III randomized, double-blind, parallel group study takes place at multiple centers and focuses on cardiopulmonary outcomes in these patients. Participants receive either the BGF MDI 320/14.4/9.6 micrograms twice daily or the GFF MDI 14.4/9.6 micrograms twice daily. The treatments are inhaled using metered dose inhalers. The study compares these two therapies over time to see how they affect the time until the first severe heart or lung event occurs. The study design ensures that neither participants nor researchers know which treatment is given to reduce bias. During the study, participants will have regular visits to the study site or virtual visits to complete assessments. Researchers will monitor lung function, symptoms, and blood tests, including blood eosinophil counts and COPD assessment test scores. The main outcome measured is the time to the first severe cardiac or COPD event, with follow-up lasting up to three years. Safety and adherence to treatment will also be closely observed throughout the study period.

Researchers are evaluating AZD0486, a bispecific antibody that targets CD19 on tumor cells and CD3 on T-cells to trigger T cell-mediated attack of malignant B cells. This phase 1 study focuses on the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of AZD0486 in adults with B-cell non-Hodgkin lymphoma, including subtypes such as diffuse large B-cell lymphoma, high-grade B-cell lymphoma, and follicular lymphoma. The study includes both relapsed/refractory patients and those with untreated follicular lymphoma meeting specific criteria. Participants receive AZD0486 as a monotherapy given intravenously. The study uses a dose escalation and optimization design to find appropriate dosing while monitoring safety and treatment effects. There are multiple cohorts based on prior treatment status and lymphoma subtype, including relapsed/refractory groups requiring at least two prior therapies and a first-line follicular lymphoma group needing treatment initiation. The treatment period includes continuous evaluation to assess drug levels and immune responses. During the study, participants undergo regular assessments including monitoring for dose-limiting toxicities, adverse events, and serious adverse events from screening until 90 days after treatment ends. Blood samples are taken to measure drug concentration and half-life. Other evaluations include measuring disease sites and confirming CD19 positivity. The study tracks participant health and treatment effects closely over the treatment and follow-up periods to understand AZD0486's safety and activity in these lymphoma types.

Researchers are evaluating treatments for participants with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplantation. This Phase 3 study compares if the combination of belantamab mafodotin, lenalidomide, and dexamethasone (BRd) can extend progression-free survival or increase the number of participants achieving minimal residual disease negative status compared with the combination of daratumumab, lenalidomide, and dexamethasone (DRd). Participants will receive either BRd or DRd treatment. Belantamab mafodotin, lenalidomide, and dexamethasone will be administered in the BRd group, while daratumumab, lenalidomide, and dexamethasone will be given in the DRd group. The study will monitor participants over approximately 7 years to assess long-term outcomes. During the study, participants will undergo assessments to measure progression-free survival and minimal residual disease status. Researchers will collect clinical data, laboratory tests, and safety information throughout the treatment and follow-up periods. The total duration of participation may last up to about 7 years to evaluate long-term effects and outcomes of the treatments.

Researchers are evaluating the combination of bleximenib, venetoclax (VEN), and azacitidine (AZA) compared to placebo with venetoclax and azacitidine alone in treating adults newly diagnosed with acute myeloid leukemia (AML) who have specific gene mutations (NPM1 or KMT2A) and are not eligible for intensive chemotherapy. This is a phase 3 randomized, double-blind, placebo-controlled study focusing on participants with AML harboring these genetic abnormalities. The study aims to assess treatment effectiveness by measuring complete remission rates and overall survival. Bleximenib and venetoclax are given orally, while azacitidine is administered either intravenously or under the skin. Participants will receive either the combination of bleximenib, venetoclax, and azacitidine or placebo with venetoclax and azacitidine, following a rigorous treatment schedule. The study includes an initial treatment period where the effects of these drugs are compared to determine their impact on AML with the given mutations. Participants will be closely monitored through regular assessments, including evaluations of remission status and survival over a period of up to 4 years and 1 month. Safety and treatment responses will be tracked throughout the study. Participants must consent to follow the study procedures and agree to contraception requirements during and after treatment. The trial involves continuous observation to gather comprehensive data on treatment outcomes and participant health.

Researchers are evaluating the effectiveness and safety of brenipatide when given along with standard care compared to a placebo with standard care in adults with bipolar disorder. This Phase 2 study aims to see if brenipatide can delay the worsening of bipolar symptoms. The trial includes participants aged 18 to 75 years and involves a careful assessment of how well the treatment works and its safety profile. The trial has three main periods: a screening period lasting about one month, a treatment period of at least six months, and a follow-up period of around two months. Participants receive either brenipatide or placebo, both given by subcutaneous injection, alongside their usual bipolar disorder medications. The study may end earlier if symptoms worsen or if participants withdraw for any reason. Participants will be asked to self-inject the study medication, maintain diaries, complete questionnaires, and attend regular visits throughout the study. Researchers will monitor the time to relapse, defined as the number of days from randomization until symptoms worsen according to specific criteria, over at least six months. Safety and adherence to treatment will also be closely observed during the study.