North Adelaide

Researchers are evaluating FMC-376 in adults with advanced solid tumors that have a specific KRAS G12C mutation. This trial aims to assess the safety, pharmacokinetics, and clinical effects of FMC-376 in patients whose tumors are locally advanced, unresectable, or metastatic. The study is conducted in three parts: Phase 1A (dose escalation), Phase 1B (dose expansion), and Phase 2 (cohort expansion), focusing on multiple dose levels in this patient population. Participants will receive FMC-376 as an oral capsule taken daily. The study explores different dosing schedules across the phases to determine optimal dosing and further evaluate the treatment's effects. The study is open-label, meaning both researchers and participants know which treatment is being administered. During the study, participants will be closely monitored for adverse events and dose limiting toxicities up to 21 days, with safety assessments continuing for approximately 24 months. Researchers will also assess pharmacokinetics and clinical activity of FMC-376. Participants must meet certain health and function criteria before and during the study to ensure safety and reliable results.

Researchers are evaluating combination chemotherapy treatments for patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) and relapsed favorable histology Wilms tumors (FHWT). This phase II trial aims to assess how adding vincristine and irinotecan to standard chemotherapy regimens affects event-free survival and overall survival compared to historical data. The study also explores kidney toxicity, tumor genetics, and radiation therapy techniques to reduce side effects in children with lung and liver metastases. Two chemotherapy regimens are studied. Arm I (Regimen UH-3) involves cycles of vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan given intravenously on specific days every 21 days. Radiation therapy is given around week 7 of cycle 3 if needed. Arm II (Regimen ICE/Cyclo/Topo) includes cycles of ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan given intravenously every 21 days, with surgery and/or radiation during certain cycles. Both arms include multiple cycles in absence of disease progression or unacceptable side effects. Participants undergo various scans like CT, PET, MRI, chest x-rays, ultrasounds, and bone scans throughout the trial. Blood samples and biopsies may be collected periodically. After treatment, patients are followed up every 3 months for the first 2 years, every 6 months for years 3-4, and once at year 5. The main outcomes measured are event-free survival and overall survival up to 5 years, along with monitoring kidney health and treatment effects.

Researchers are evaluating the long-term effects of sepiapterin on preserving brain function in children with phenylketonuria (PKU) when treatment starts early in childhood. This Phase 3b open-label study aims to understand how sepiapterin impacts neurocognitive outcomes over time in these young patients. The study includes two parts: an initial test to see how participants respond to sepiapterin and a longer treatment period to monitor ongoing effects. Sepiapterin is given orally as a powder mixed with water or apple juice. In Part 1, participants undergo an open-label sepiapterin-responsiveness test. Part 2 involves an open-label treatment phase where sepiapterin is administered over an extended period to assess its impact on neurocognitive function. The study enrolls children up to 9 years old diagnosed with PKU and monitors their response to the medication during these phases. Participants will have assessments including intelligence tests at the start and after two years to measure changes in cognitive function. Researchers will monitor safety, medication adherence, and other health indicators throughout the study. Blood tests and pregnancy tests for women of childbearing potential are also conducted. The main outcomes focus on changes in intelligence quotient scores measured by standardized tests at baseline and year 2 to evaluate sepiapterin's effect on neurocognitive preservation.

Researchers are evaluating the effectiveness of zanubrutinib combined with anti-CD20 antibodies compared to lenalidomide plus rituximab (R2) in adults with relapsed or refractory follicular lymphoma (FL) or marginal zone lymphoma (MZL). The study aims to measure progression-free survival using independent review committees and established lymphoma response criteria based on PET/CT and CT imaging. Participants will receive zanubrutinib orally either as 160 mg twice daily or 320 mg once daily in continuous 28-day cycles. In the zanubrutinib plus rituximab group, rituximab is given intravenously at 375 mg/m2 on Days 1, 8, 15, and 22 of Cycle 1 and Day 1 of Cycles 2 to 5, each cycle lasting 28 days. The comparator group receives lenalidomide orally at 20 mg daily on Days 1 to 21 of each 28-day cycle for 12 cycles, plus obinutuzumab intravenously at 1000 mg on Cycle 1 Days 1, 8, 15 and Cycles 2 to 6 Day 1. During the study, participants will undergo imaging assessments such as PET/CT and CT scans to evaluate disease progression. Researchers will monitor treatment response and safety over approximately 78 months. Progression-free survival is the primary outcome, measured by a blinded independent review committee. Participants are expected to have measurable disease and adequate organ function at enrollment, with ongoing assessments to track treatment effects and adverse events.

Researchers are studying the safety and effectiveness of tividenofusp alfa (DNL310), a new enzyme-replacement therapy designed to enter the central nervous system, for children and young adults with mucopolysaccharidosis type II (MPS II), including both neuronopathic and non-neuronopathic forms. This Phase 2/3 trial compares tividenofusp alfa to the standard treatment idursulfase, aiming to better understand its impact on this rare genetic condition. Participants receive either tividenofusp alfa or idursulfase through intravenous infusions as repeated doses. The study has a double-blind, randomized design with two groups receiving these treatments. Based on specific criteria, participants may also have the opportunity to enter an open-label phase where they receive either DNL310 or idursulfase openly. During the study, researchers will measure changes in cerebrospinal fluid heparan sulfate levels after 24 weeks to assess biochemical effects. They will also evaluate behavioral and adaptive functioning using the Vineland Adaptive Behavior Scale over 96 weeks. The study includes careful monitoring for safety and treatment response, with participants ranging from 2 to less than 26 years old involved in the trial.

Researchers are evaluating the safety and effectiveness of oral nizubaglustat (AZ-3102) in treating children and young people with late-infantile and juvenile forms of GM1 or GM2 gangliosidosis, rare inherited metabolic disorders. This Phase 3 study is designed as a double-blind, randomized, placebo-controlled trial lasting 18 months. It aims primarily to show improvements in ataxic symptoms, with additional goals to assess other neurological effects, the drug's behavior in the body, and its safety and tolerability. Participants will receive either oral nizubaglustat or a placebo daily over the 18-month treatment period. The study is conducted at multiple centers and includes careful monitoring of the drug's levels in the body and its impact on disease manifestations. The design ensures that neither the participants nor the researchers know which treatment is being given until the study concludes. During the study, participants will undergo assessments to measure changes in ataxia scores from baseline to month 18, along with evaluations of other functional symptoms. Safety will be closely monitored throughout. The total duration of participation is 18 months, during which researchers will collect data on neurological function, drug effects, and any side effects experienced by participants.

This research aims to assess the safety and effectiveness of oral nizubaglustat (AZ-3102) in treating late-infantile and juvenile forms of Niemann-Pick type C disease. It is an 18-month, double-blind, randomized, placebo-controlled, multicenter Phase 3 study focused on improving ataxic symptoms compared to placebo. Additional goals include evaluating other neurological symptoms, pharmacokinetics, pharmacodynamics, and overall safety and tolerability of the treatment. Participants will receive either oral nizubaglustat or a matching placebo once daily for 18 months. The study compares these two groups to measure the impact on ataxic manifestations and other disease symptoms. Pharmacokinetic assessments occur after the first dose and at steady state during multiple dosing. Safety monitoring continues throughout the treatment period. During the study, participants will undergo various assessments including the Scale for the Assessment and Rating of Ataxia (SARA) to measure changes in ataxia severity from baseline to month 18. Additional evaluations include functional assessments, safety monitoring, and tolerability checks. Researchers will also collect data on drug effects and side effects to understand how the treatment influences the disease over time.

Researchers are conducting an 18-month, Phase 3, randomized, double-blind, placebo-controlled, multicenter study to assess the safety and effectiveness of oral nizubaglustat (AZ-3102) in children and adolescents with late-infantile and juvenile forms of Niemann-Pick type C disease, GM1 gangliosidosis, or GM2 gangliosidosis. The study uses a Master Protocol Research Program where participants are assigned to different subprotocols according to their specific disease type. Additional details about eligibility, safety, and efficacy assessments are provided in disease-specific subprotocols. Participants will receive either oral nizubaglustat tablets or a matching placebo following the assigned subprotocol regimen. The study includes separate subprotocols for Niemann-Pick type C disease and for GM1 or GM2 gangliosidosis, each with its own specific procedures and endpoints. The treatment period lasts for 18 months, during which safety and efficacy are evaluated. Participants will be monitored and assessed throughout the 18-month treatment period, with evaluations tailored to the specific subprotocol. Researchers will measure the number of participants assigned to each subprotocol and track safety and efficacy outcomes. For detailed procedures and endpoints, participants and caregivers are referred to the corresponding clinical trial records for each disease subtype.

This research aims to evaluate the effectiveness and safety of a fixed-dose combination of fluticasone propionate (Fp) and albuterol sulfate (ABS) delivered via an integrated electronic module multidose dry powder inhaler (eMDPI) compared to ABS alone in reducing severe clinical asthma exacerbations in patients with asthma. The study also assesses the efficacy of a low dose of Fp/ABS versus ABS and examines the impact on systemic corticosteroid exposure. This is a phase 3 randomized, double-blind, active-controlled trial involving patients diagnosed with asthma for at least one year. Participants will receive either a high dose or low dose of Fp/ABS or ABS alone through oral inhalation powder during a double-blind treatment period lasting a minimum of 24 weeks. The study includes a 2-week screening phase, a 2 to 4-week run-in period, and the treatment phase. Because this is an event-driven study, the total duration for individual participants may extend up to approximately 42 months depending on enrollment timing and study completion. During the study, participants will be closely monitored for time to first severe clinical asthma exacerbation while using the inhaler device. Safety and tolerability will be evaluated throughout the study. Researchers will also track systemic corticosteroid use and overall asthma control. The minimum participation time is 28 weeks, including screening and run-in, with extended monitoring possible based on study events and criteria.

Fetal growth restriction (FGR) affects many pregnancies and is a major risk factor for stillbirth, preterm birth, and long-term health problems including brain injury. This trial studies whether giving melatonin to pregnant women with early-onset severe FGR can protect the fetal brain and improve children's neurodevelopmental outcomes. It is a phase 3, triple-blind, randomized, placebo-controlled trial involving multiple centers in Australia and New Zealand. Participants receive either melatonin tablets (10 mg three times daily, up to 30 mg per day) or placebo tablets that look identical but contain no active ingredient. Treatment begins after diagnosis of severe FGR between 23 and 31+6 weeks of pregnancy. The study includes sub-analyses based on gestational age at diagnosis to compare effects in early versus late-onset FGR. Throughout the study, children's neurodevelopment will be measured at 2 years of age. Researchers will monitor maternal and fetal health, fetal wellbeing, and collect data on birth outcomes. The main outcome is neurodevelopmental performance assessed between 24 and 36 months corrected age. Safety and tolerability of melatonin supplementation during pregnancy will also be evaluated over the course of the trial.