North Adelaide

Researchers are evaluating the drug FMC-376 in adults with advanced solid tumors that have a specific KRAS G12C mutation. This clinical trial is designed in three parts Phase 1A dose escalation, Phase 1B dose expansion, and Phase 2 cohort expansion, to study various dose levels in participants with these tumors. The trial focuses on tumors that are locally advanced, unresectable, or metastatic, including types like non-small cell lung cancer, colorectal cancer, and pancreatic cancer. Participants will receive FMC-376 orally as a daily capsule in 21-day cycles during the dose escalation, dose expansion, and cohort expansion phases. The study does not include placebo or blinded treatments. The trial aims to assess the safety, pharmacokinetics how the drug is absorbed and processed, and clinical activity of FMC-376 at multiple dose levels. During the study, participants will be monitored closely for dose-limiting toxicities within the first 21 days and adverse events for approximately 24 months. Researchers will measure drug levels in the blood, response rates, duration of response, disease control, progression-free survival, and overall survival. Participants will undergo regular assessments including laboratory tests and evaluations to track safety and treatment effects throughout the study period.

Researchers are evaluating how well combination chemotherapy works in treating patients with newly diagnosed stages 2 to 4 diffuse anaplastic Wilms tumor DAWT and patients with relapsed favorable histology Wilms tumor FHWT. This phase II trial compares the effects of two chemotherapy regimens, UH-3 and ICECycloTopo, on event-free survival and overall survival, aiming to improve outcomes based on different relapse risk groups and prior treatments. The study also explores kidney toxicity, genetic markers, surgery impacts, and radiation therapy techniques to reduce side effects and better understand tumor behavior. Participants are assigned to one of two treatment groups. In Arm I Regimen UH-3, patients receive cycles of vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan intravenously over various days in a 21-day cycle, with radiation therapy at week 7 of cycle 3 if needed. In Arm II Regimen ICECycloTopo, patients receive cycles of carboplatin, etoposide, ifosfamide, cyclophosphamide, and topotecan intravenously over 10 cycles every 21 days, with surgery andor radiation therapy during certain cycles as clinically indicated. Throughout the trial, patients undergo multiple imaging tests including CT scans, PET scans, chest x-rays, MRIs, abdominal ultrasounds, and bone scans, along with blood sample collections and biopsies. After completing treatment, follow-up visits occur every 3 months for the first 2 years, then every 6 months for years 3 and 4, and once at year 5. The main outcomes measured are event-free survival and overall survival up to 5 years from study entry, with ongoing monitoring for treatment effects and safety.

Researchers are evaluating a phase II trial studying how well lower dose radiotherapy after chemotherapy works in treating children and young adults with central nervous system CNS germinomas. This trial aims to compare reduced radiation doses to standard treatment while maintaining effectiveness, potentially reducing long-term side effects. The study also investigates survival rates, tumor response, neuroendocrine function, and cognitive processing speed in participants with localized, metastatic, and basal ganglia or thalamic germinomas. Participants receive chemotherapy with carboplatin and etoposide intravenously over several days, repeated every 21 days for up to four cycles. After chemotherapy, patients are assigned to different treatment groups strata based on tumor response and location. Radiation therapy is delivered using advanced techniques such as 3D conformal radiation, proton therapy, or intensity-modulated radiation daily on weekdays for 16 to 24 days depending on the stratum. Some patients may undergo second-look surgery. The study includes collection of blood, cerebrospinal fluid, and tumor tissue samples for research. Throughout the study, participants undergo MRI scans and may have lumbar punctures for cerebrospinal fluid collection. Follow-up occurs every three months for the first year, then every four months for two years, and annually up to ten years. Researchers measure event-free survival, overall survival, tumor response, neuroendocrine function, and cognitive processing speed at multiple time points. The study also monitors for cerebral vascular events and evaluates long-term cognitive, social, and behavioral outcomes.

Researchers are evaluating the long-term effects of sepiapterin on preserving neurocognitive function in children with phenylketonuria PKU, focusing on treatment started in early childhood. This Phase 3b open-label study aims to assess whether sepiapterin can maintain intelligence scores and quality of life over several years in young participants with PKU. The study has two parts an initial open-label sepiapterin-responsiveness test followed by a longer open-label treatment period. Participants will receive sepiapterin orally once daily, with doses adjusted by age and weight, for up to six years. The sepiapterin powder will be mixed with water or apple juice before administration. Throughout the study, children will undergo regular assessments including intelligence quotient IQ testing at baseline, 2 years, and 4 years, as well as quality of life questionnaires and blood phenylalanine level measurements up to six years. Researchers will monitor cognitive function, quality of life, and blood markers associated with PKU, with the study concluding in 2031.

The trial investigates the effects of a combination treatment using Fluticasone Furoate FF, Umeclidinium UMEC, and Vilanterol VI on lung function compared to a combination of FF and VI alone. The study focuses on adolescents aged 12 to 17 years with asthma that is not adequately controlled despite stable maintenance therapy with inhaled corticosteroids and long-acting beta2-agonists. The research aims to assess efficacy, safety, tolerability, and pharmacokinetics over a 24-week period in this age group. Participants receive either the FFUMECVI combination or the FFVI combination, both administered via the ELLIPTA inhaler. The study is randomized, double-blind, and conducted in parallel groups. Treatments are given daily, and the trial lasts for 24 weeks to monitor the effects on lung function and asthma control. During the study, participants undergo lung function tests measuring forced expiratory volume in 1 second FEV1 at the start and after 24 weeks. Additional assessments include asthma control questionnaires at baseline and week 24 to evaluate changes in symptoms. Safety and tolerability are monitored throughout, with the total participation lasting 24 weeks.

Researchers are evaluating the efficacy and safety of tividenofusp alfa DNL310, an investigational enzyme-replacement therapy that can penetrate the central nervous system, compared with the standard enzyme replacement treatment idursulfase in children and young adults with mucopolysaccharidosis type II MPS II, which includes neuronopathic and non-neuronopathic forms. This Phase 23, double-blind, randomized, controlled study also allows some participants to enter an open-label treatment phase based on specific criteria. The study includes two main groups Cohort A with participants aged 2 to under 6 years who have neuronopathic MPS II, and Cohort B with participants aged 6 to under 26 years who have non-neuronopathic MPS II. Both tividenofusp alfa and idursulfase are given by repeated intravenous doses. Participants who meet certain criteria may continue treatment in an open-label phase with either DNL310 or idursulfase. Participants will be closely monitored through various assessments during the study, including measurements of cerebrospinal fluid heparan sulfate levels, adaptive behavior scales, developmental tests, walking distance tests, and imaging for liver and spleen volume. Caregiver impressions of change are also collected. The primary outcomes are assessed at 24 and 96 weeks, with additional secondary outcomes measured up to 48 or 96 weeks. The study is designed to last until December 2027, ensuring thorough evaluation of safety and treatment effects.

Researchers are conducting an 18-month Phase 3 study to evaluate 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. This randomized, double-blind, placebo-controlled trial aims to show whether nizubaglustat improves ataxic symptoms compared with placebo. The study also assesses other neurological and behavioral effects, pharmacokinetics, pharmacodynamics, and safety of the treatment. Participants receive either daily oral dispersible tablets of nizubaglustat or matching placebo. The study follows a parallel design with random assignment to treatment groups. The treatment period lasts for 18 months, during which participants take the assigned medication once daily. The study monitors treatment effects and safety throughout this period. During the trial, participants undergo assessments including the Scale for the Assessment and Rating of Ataxia SARA, Vineland Adaptive Behavior Scale, Penetration-Aspiration Scale, 9-Hole Peg Test, and other neurological and functional tests at baseline and at months 6, 12, and 18. Blood samples are collected to study drug levels and biomarkers. Researchers also track seizure frequency and adverse events. The primary outcome measures focus on changes in total and functional SARA scores from baseline to month 18, with safety and tolerability evaluated throughout participation.

Researchers are conducting an 18-month Phase 3 study to evaluate the safety and efficacy of oral nizubaglustat AZ-3102 in children aged 4 years and older diagnosed with late-infantile or juvenile forms of Niemann-Pick type C disease, GM1 gangliosidosis, or GM2 gangliosidosis. This randomized, double-blind, placebo-controlled, multicenter trial uses a Master Protocol Research Program to study these related conditions in separate subprotocols based on disease type. Participants are randomly assigned in a 21 ratio to receive either oral nizubaglustat tablets or a matching placebo. The treatment and procedures are specific to each disease subprotocol, detailing different eligibility requirements, safety assessments, and efficacy endpoints. The study includes subprotocols for Niemann-Pick type C disease and for GM1 or GM2 gangliosidosis, each with tailored treatment plans and monitoring. Throughout the study, participants will undergo evaluations as described in their respective subprotocols, which may include clinical assessments, safety monitoring, and outcome measurements over the 18-month period. Researchers will track participant allocation to each subprotocol as the primary outcome. The trial is designed to monitor safety and treatment effects closely until the study completes in 2028, with detailed procedures provided within each disease-specific subprotocol.

Researchers are investigating nerandomilast in children and adolescents aged 2 to 17 years who have fibrosing interstitial lung disease ILD. Nerandomilast has already been approved for adults with idiopathic pulmonary fibrosis, and this study aims to understand how the drug is tolerated, processed by the body, and whether it may help younger patients with ILD. The study includes both younger children and older childrenadolescents in different treatment groups to assess these questions. Participants aged 6 to 17 years are randomly placed into one of two groups one receiving nerandomilast and the other a placebo, with twice as many participants receiving nerandomilast. They take tablets twice daily for six months, then all receive nerandomilast for at least two years. Children aged 2 to 5 years receive nerandomilast from the start for at least two and a half years. The total study duration varies between two and a half and five years depending on when participants join. During the study, participants may visit the study site about 18 to 30 times. Doctors collect blood samples to monitor health and drug processing, assess lung function, growth, and quality of life, and track any changes in health. For those aged 6 to 17 years, comparisons between the nerandomilast and placebo groups help evaluate potential treatment effects. Safety and treatment-related side effects are closely monitored throughout the study period.

Researchers are evaluating the safety, side effects, and optimal dose of cabozantinib combined with standard chemotherapy in patients newly diagnosed with osteosarcoma. This phase IIIII trial aims to compare the effects of adding cabozantinib, a kinase inhibitor that may slow tumor growth, to the usual chemotherapy drugs methotrexate, doxorubicin, and cisplatin. The study focuses on patients under 40 years old with high-grade osteosarcoma, including both localized and metastatic cases. Participants receive treatment in two main phases. The feasibility phase now closed tested cabozantinib with chemotherapy in metastatic patients with resectable tumors, using cycles of oral cabozantinib and intravenous chemotherapy drugs over several months. The ongoing efficacy phase randomly assigns patients to either standard chemotherapy alone or chemotherapy combined with cabozantinib, with treatment divided into induction, consolidation, and maintenance cycles lasting 35 or 28 days each. Imaging scans, blood samples, and surgery are part of the treatment and evaluation process. During the study, participants undergo regular assessments including X-rays, CT scans, MRI, PET or bone scans, and blood sample collection at diagnosis and throughout treatment. Researchers monitor event-free survival, overall survival, symptom burden, and side effects reported by patients. The trial lasts up to 5 years after treatment to assess long-term outcomes, gather tumor and blood samples for further biological studies, and evaluate the impact of cabozantinib addition on patient health and response.