Perth

Researchers are conducting a prospective multicenter, open-label, dose-escalation trial to evaluate the safety, tolerability, and pharmacodynamics of 4D-310 in adults with Fabry Disease who have cardiac involvement. The study includes both males and females aged 18 to 65 years. Fabry Disease is a genetic condition, and this trial focuses on participants with a confirmed pathogenic GLA mutation and cardiac symptoms related to the disease. Participants will receive a single intravenous (IV) dose of the gene therapy 4D-310. The trial is designed to carefully escalate the dose to monitor effects and safety. This study does not involve repeated dosing but focuses on the effects following one administration of the therapy. During the study, participants will be monitored for adverse events over the course of one year to assess both the incidence and severity of any side effects. Other evaluations will include safety assessments and pharmacodynamic measurements to understand how the therapy affects the body. The total involvement period includes this year-long follow-up to gather comprehensive safety data.

Researchers are evaluating new treatments for people with high-risk non-muscle invasive bladder cancer (HR NMIBC), a type of bladder cancer that has not spread to the muscle but has a high chance of worsening or returning. This cancer type may include carcinoma in situ (CIS), which is a flat, surface-level bladder cancer. The study aims to learn whether adding intismeran autogene (V940), a treatment designed to boost the immune system's attack on cancer, to the standard Bacillus Calmette-Guerin (BCG) immunotherapy can help people live longer without the cancer growing, spreading, or coming back. Participants will receive either the combination of V940 with BCG or BCG alone. BCG is given as a bladder instillation, while V940 is given as an intramuscular injection. The study is phase 2, open-label, and randomized. As of a 2026 amendment, outcome measures for a monotherapy arm of V940 are no longer primary or secondary. Treatment is focused on Cohort A, which includes people with high-risk non-muscle invasive bladder cancer who are BCG-naïve or meet specific recurrence criteria. During the study, participants will be monitored for event-free survival for up to approximately 5 years. Researchers will assess how long participants live without the cancer worsening or returning. The study includes regular evaluations, imaging, and safety monitoring. The total duration of participation depends on individual outcomes and follow-up but includes long-term observation to assess treatment effects and safety.

Researchers are evaluating the safety of aerosolized RSP-1502 in people with cystic fibrosis who have chronic lung infections caused by Pseudomonas aeruginosa. This phase 1b/2a study compares different doses of RSP-1502 to an active control, aiming to find the maximum tolerated dose (MTD) and assess safety outcomes. Participants must meet specific lung function and infection criteria to join the study. The study involves administering RSP-1502 or an active control solution by inhalation using a nebulizer for 14 days. RSP-1502 contains tobramycin and CaEDTA in a sterile solution, while the active control is a tobramycin inhalation solution. After dose escalation to identify the MTD, a dose expansion phase compares the MTD of RSP-1502 to the active control for another 14 days. Participants will then be followed for 14 days after treatment ends. Participants will have their lung function tested with spirometry and undergo electrocardiograms on specific days during treatment. Researchers will monitor for any treatment-related adverse events and serious adverse events throughout the 28-day treatment and follow-up period. They will also track pulmonary exacerbations and other safety measures. The total participation includes dosing and a 14-day follow-up after treatment completion.

Researchers are investigating new treatments for children and young people with relapsed or refractory B-cell non-Hodgkin Lymphoma (B-NHL), a type of cancer affecting lymph nodes and organs like the liver or spleen. Current treatments have limited success and many side effects, curing only about 30% of patients. This global trial aims to find better and safer medicines by testing novel agents in this rare cancer setting, using an adaptive trial design that allows continuous evaluation and adjustment. The trial has three treatment groups, each testing a different new medicine: bispecific antibodies (BsAbs), antibody-drug conjugates (ADC) combined with standard chemotherapy, and chimeric antigen receptor (CAR) T-cells. Patients may be assigned to any available group they qualify for, and if a treatment does not work, they might switch to another group. The trial uses a Bayesian adaptive design to efficiently decide whether a treatment is effective and can stop ineffective treatments early to introduce new ones. Participants will receive the assigned treatments and be monitored closely through scans, biopsies, and laboratory tests to evaluate disease response and safety. The main outcomes include measuring objective responses and complete remissions at specified time points. Children and young people will be followed for at least two years after treatment to monitor for side effects and long-term health. The study includes comprehensive assessments and is conducted across multiple international centers.

This research aims to collect long-term safety and effectiveness data for participants treated with ibrutinib, a medicine used for various blood cancers and conditions including Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Diffuse Large B-cell Lymphoma, Waldenstrom Macroglobulinemia, and Chronic Graft Versus Host Disease. It also provides ongoing access to ibrutinib for participants who have completed previous ibrutinib studies, continue treatment, and benefit from it. This is an open-label Phase 3b study without formal hypothesis testing. Participants will continue their current ibrutinib dosing regimen from the prior study, taken orally once daily as capsules in doses of 560 mg, 420 mg, 280 mg, or 140 mg, around the same time each day. Treatment continues until the investigator decides the participant no longer benefits due to disease progression or side effects, the participant withdraws, alternative ibrutinib access becomes available, or the study ends. Participants not able to access ibrutinib elsewhere can keep receiving the single-agent ibrutinib until all transition or stop treatment, or until the study is stopped. During the study, safety is monitored throughout and summarized, and effectiveness may be analyzed together with previous study data. The main outcome measured is the number of participants experiencing any adverse events within 30 days after the last dose or until starting another cancer treatment. Participants will undergo assessments including pregnancy testing and investigator evaluations to ensure ongoing benefit and safety. The study duration depends on when participants stop treatment or transition to other access.

Researchers are studying the prevalence, risk factors, and effects of chronic post-surgical pain in children aged 0 to 16 years undergoing common pediatric surgeries such as laparoscopic appendicectomy, scrotal exploration, orchidopexy, hypospadias repair, and circumcision. The study aims to understand how factors like parent and child anxiety, existing pain, and acute post-operative care relate to the development of chronic pain over time. This knowledge will help improve care and reduce the risk of long-term pain in children after surgery. The study involves completing questionnaires at six different times, starting before surgery, then at Day 2, 3-4 weeks, 3-4 months, and finally 10-12 months post-surgery. These questionnaires assess pain levels, function, and related factors. The study is conducted across multiple international centers and focuses on both elective and emergency surgeries. Participants will be involved in providing information through these questionnaires over about one year. Researchers will measure outcomes like the presence of chronic pain 10-12 months after surgery. The study will also monitor the impact of chronic pain on children's quality of life, emotional well-being, and social functioning. Families unable to complete follow-up surveys or those with language barriers may not participate, ensuring accurate and complete data collection.

Researchers are evaluating the drug OKN4395 given alone and combined with pembrolizumab in patients with advanced solid tumors. This Phase 1 study aims to determine how safe and tolerable OKN4395 is, both by itself and with pembrolizumab, while also measuring drug levels in the blood and the drug's cancer-fighting effects. The study includes patients with various solid tumors, including sarcoma, pancreatic adenocarcinoma, non-small cell lung cancer, colorectal cancer, and head and neck squamous cell carcinoma, especially when other treatments have failed or are not suitable. The study has two parts. Part 1a tests increasing doses of OKN4395 alone or with pembrolizumab given on day 1 every 21-day cycle, with doses rising after safety reviews, ranging from 10 mg twice daily up to 450 mg twice daily. Part 1b involves five groups focusing on specific cancers, with some receiving OKN4395 alone and others combined with pembrolizumab. In Part 1b, some groups will explore how food or stomach pH affects the drug's blood levels. Treatments include oral OKN4395, intravenous pembrolizumab every three weeks, and some participants may receive famotidine or food before dosing. Participants will be closely monitored for side effects, including dose-limiting toxicities, treatment-emergent adverse events, serious adverse events, ECG abnormalities, and lab test changes over up to 27 months in Part 1a and about 12 months in Part 1b. Tumor response will also be measured. Regular blood tests, biopsies, and imaging will be done, and participants must be able to swallow the oral drug and comply with study requirements. The study plans to enroll about 166 participants across multiple countries including the US, Australia, UK, and EU.

Researchers are evaluating the safety, tolerability, how the body processes, and effectiveness of TERN-701, a selective allosteric inhibitor targeting BCR-ABL1, in adults with chronic phase chronic myeloid leukemia (CP-CML) who have been previously treated. The study is divided into two parts: Part 1 focuses on dose escalation to find safe dosage levels, and Part 2 involves randomized dose expansion to further assess the chosen doses and includes a mutation cohort for participants with certain resistance mutations. Participants in both parts will take TERN-701 orally once daily in 28-day cycles. Part 1 involves sequential dose escalation cohorts, while Part 2 evaluates two recommended dose levels selected from Part 1. The mutation cohort (Part 2m) will assess a specific 500 mg dose in participants with particular resistance mutations. Scheduled visits occur frequently during the first treatment cycle and then regularly throughout the study to monitor treatment effects. During the study, participants will have regular visits for evaluations including safety checks and laboratory tests. Researchers will measure dose-limiting toxicities, adverse events, hematologic response, molecular response, and changes in BCR-ABL1 transcript levels up to three years. The trial plans to enroll about 180 participants, with up to 80 in Part 1, about 80 in Part 2, and around 20 in the mutation cohort. All participants will receive the active treatment throughout the study duration.

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, tolerability, and effectiveness of sonrotoclax alone and combined with other drugs in patients with relapsed or refractory multiple myeloma with a specific chromosomal translocation called t(11;14). This Phase 1b/2 study focuses on patients whose disease has returned or not responded to previous treatments, aiming to understand how well sonrotoclax works in these settings. The study assesses sonrotoclax given by mouth daily, either alone or combined with dexamethasone (given once weekly by mouth or intravenously), carfilzomib (weekly intravenous), daratumumab (weekly under the skin), or pomalidomide (daily by mouth). Different combinations are tested to find safe and effective dosing. The study includes dose-escalation and cohort-expansion phases to explore various treatment regimens. Participants will be closely monitored for side effects and treatment responses over time. Researchers will track dose-limiting toxicities during the first 28 days, adverse events up to 30 days after the last dose, and long-term responses over approximately 4 years. Assessments include measuring disease markers and overall response rates. Safety and efficacy data will guide future treatments for this patient population.