Parkville

Researchers are evaluating the safety and effects of marstacimab, a study medicine, for potential treatment of hemophilia in boys and male children aged 1 to 17 years. The trial focuses on those with severe Hemophilia A or moderately severe to severe Hemophilia B, including participants with or without inhibitors. The study aims to compare participants experiences with marstacimab to their historical bleeding episodes without the medicine. All participants will receive weekly subcutaneous injections of marstacimab. The first dose is administered at the study site by staff, and subsequent doses can be given at home or by study staff during the 12-month treatment period. Enrollment opens sequentially by age groups, starting with adolescents 12-17 years, followed by children 6-11 years, and finally children 1-5 years. The study includes about 1 month of screening, 12 months of treatment, and 1 month of follow-up. Participants will visit the study site at least 10 times during the study, with the option for two visits to occur at home if allowed. They will also receive six phone calls approximately every two months. Researchers will monitor bleeding rates, adverse events, injection site reactions, and immune responses. The overall participation lasts about 14 months, including screening, treatment, and follow-up periods.

Researchers are evaluating the safety, tolerability, and effectiveness of Navepegritide TransCon CNP in infants with genetically confirmed achondroplasia ACH who are younger than 2 years old. This Phase 2, multicenter, double-blind, randomized, placebo-controlled trial aims to compare weekly doses of Navepegritide with a placebo over a 52-week period to understand its impact on growth and safety in this population. Participants receive once-weekly subcutaneous injections of either 100 bcgkg Navepegritide or a placebo for 52 weeks. The study is randomized in a 21 ratio, with some infants receiving the active drug and others receiving placebo injections. After the 52-week treatment period, there is an open-label extension phase allowing continued evaluation. During the study, infants will be monitored through medical history reviews, physical exams, vital signs, ECGs, imaging, and lab tests to evaluate safety and growth changes. The main outcomes measured are the safety and tolerability of Navepegritide and its effect on growth over 52 weeks. Parents or caregivers will administer weekly injections and follow study instructions, including vitamin D supplementation where applicable. The total participation time includes the initial 52 weeks of treatment followed by further observation during the extension period.

Researchers are investigating the long-term outcomes of children and young people who completed an 18-month course of oral immunotherapy OIT for peanut, egg, or milk allergy. The study aims to compare changes in health-related quality of life HRQL up to 5-15 years after stopping OIT, focusing on participants who achieved remission and those who did not. This observational study involves participants from four earlier clinical trials related to OIT treatment for these allergies. Participants will attend one follow-up visit where several tests and evaluations will take place. These include a blood test to measure specific immunoglobulin E sIgE levels related to peanut, egg, or milk allergies, and a skin prick test to assess allergy status using various extracts like histamine, saline, house dust mite, rye grass, and the relevant food allergen. Blood collection may be via venipuncture or fingerprick depending on feasibility. Plasma and blood cells will be stored for future research. During the single study visit, participants will complete allergy questionnaires, and blood and skin tests will be conducted to gather data on immune markers and allergy status. Researchers will measure changes in HRQL and the incidence and severity of allergic reactions over the years following OIT. The visit is expected to last about two hours, and results will help understand the long-term effects of OIT on food allergy remission and quality of life.

Researchers are evaluating the long-term safety of JNT-517 in children and adults with Phenylketonuria PKU, a condition caused by a deficiency in the PAH enzyme. This Phase 3, open-label study includes participants who completed previous JNT-517 studies as well as those new to JNT-517 treatment. The goal is to understand how the drug performs over an extended period when used consistently in this population. All participants will receive JNT-517 orally twice daily with doses adjusted for age and weight. The study will follow a fixed dosing schedule regardless of prior exposure to JNT-517. Participants will be monitored for treatment-emergent adverse events and changes in blood and urine phenylalanine levels, dietary intake, and attention-related symptoms among children previously treated. Participants will attend regular visits for safety assessments, blood tests, dietary evaluations, and symptom rating scales. Plasma drug concentrations will be measured at specific times in younger children to understand drug levels. The study tracks adverse events from screening through two weeks after the last dose. Total participation duration may last up to approximately five years, allowing long-term safety and efficacy monitoring.

Researchers are evaluating whether retatrutide and tirzepatide can prevent major adverse liver outcomes in adults with metabolic dysfunction-associated steatotic liver disease MASLD who are at high risk based on non-invasive tests. This Phase 3 randomized controlled trial aims to assess these treatments compared to placebo in about 4,500 adults over approximately 224 weeks. The study is sponsored by Eli Lilly and Company and focuses on liver disease progression and related health measures. Participants will be randomly assigned to receive retatrutide, tirzepatide, or placebo, all administered by subcutaneous injection. The trial includes two placebo groups corresponding to each experimental drug. After completing the main study, eligible participants may join a 2-year extension where all will receive either retatrutide or tirzepatide regardless of their initial assignment. During the study, participants may attend around 25 to 30 clinic visits for health monitoring, study procedures, and assessments of liver function and disease status. Researchers will measure the time to major adverse liver outcomes, changes in liver fibrosis scores, liver stiffness, liver fat content, liver enzyme levels, body weight, and cardiovascular events. Monitoring will continue from baseline through study completion, with detailed evaluations at multiple timepoints including week 104.

This research aims to observe and track growth patterns and the clinical progression of Hypochondroplasia HCH in children. It focuses on collecting various growth measurements and other relevant data over time to better understand this condition. The study is sponsored by BioMarin Pharmaceutical and involves children diagnosed with Hypochondroplasia, up to 15 years old. Participants include children confirmed to have Hypochondroplasia through genetic testing. The study is observational, meaning there are no experimental treatments involved. Children will be monitored regularly to record changes in growth and body proportions, with data collection occurring every six months over the course of the study, which may last up to 15 years. Throughout the study, children will undergo assessments every six months to measure growth velocity, height, body mass index BMI, and body segment ratios. Quality of life and severity impressions from both patients and caregivers will be evaluated annually. Researchers will also track medical events, use of growth hormone treatments, and any limb lengthening surgeries. This long-term follow-up allows for comprehensive monitoring of growth and health outcomes in children with Hypochondroplasia.

Researchers are evaluating the safety and tolerability of NKX019, an investigational allogeneic CD19-directed CAR NK cell therapy, in adults with autoimmune diseases such as Lupus Nephritis and Primary Membranous Nephropathy. This Phase 12, open-label, multi-center study uses a dose escalation design to find recommended doses and assess preliminary effects, pharmacokinetics, and pharmacodynamics. Participants undergo a treatment cycle starting with lymphodepletion using fludarabine and cyclophosphamide or cyclophosphamide alone if cytopenic, followed by three doses of NKX019. The study uses a 33 dose escalation to determine safe dosing and includes dose expansion cohorts. The treatment aims to evaluate the impact of NKX019 on autoimmune disease activity and kidney function. During the study, participants are closely monitored for dose-limiting toxicities, adverse events, and lab abnormalities from the first dose until follow-up. Researchers assess kidney response, disease activity scores, and drug levels in blood for up to two years after infusion. Immunogenicity and effects on background therapies are also evaluated. The total participation time varies based on follow-up assessments and treatment response.

Researchers are evaluating the safety and effectiveness of RLY-2608, a mutant-selective oral PI3K inhibitor, in adults and children with PIK3CA Related Overgrowth Spectrum PROS and malformations driven by PIK3CA mutation. This Phase 2 study has three parts Part 1 focuses on dose selection, Part 2 includes exploratory single-arm cohorts for different participant groups, and Part 3 is a randomized, double-blinded study comparing RLY-2608 to a placebo. Participants receive RLY-2608 orally in various doses depending on their age group and study part. Children aged 2 to under 6 years and 6 to under 12 years undergo dose escalation to find the recommended dose, while older participants receive established doses. Part 3 involves randomization to either RLY-2608 or placebo for participants aged 6 years and older. Each part includes dosing cycles and treatment schedules designed to assess safety and efficacy. During the study, participants undergo assessments including lesion volume measurements, blood tests, ECGs, and biopsies to confirm PIK3CA mutation status. Researchers monitor adverse events and treatment effects through regular visits and imaging at baseline, Week 12, and Week 24. Patient-reported outcomes and quality of life measures are also collected monthly in Part 3. The study spans several years, with ongoing safety and efficacy evaluations throughout treatment and follow-up periods.

This research aims to evaluate the effects of different doses of vosoritide and compare the therapeutic dose of vosoritide to human growth hormone hGH in children diagnosed with idiopathic short stature ISS. The study is a Phase 2, randomized, controlled trial that seeks to understand how these treatments influence growth in affected children. Participants will first undergo a minimum 6-month observation period to assess their baseline growth. Then, those assigned to the vosoritide and placebo groups will receive randomized treatment for at least 6 months, with placebo limited to a maximum of 6 months. After this, open-label vosoritide treatment will continue until participants reach near-final adult height or at least 16 years for females and 18 years for males, whichever is later. Participants randomized to the hGH group will receive open-label hGH treatment for a minimum of 4 years. Study treatments involve daily injections. Throughout the study, participants will attend regular visits for clinical and imaging assessments, including evaluations of hips and lower extremities. Researchers will monitor safety concerns such as hypotension, fractures, and slipped capital femoral epiphysis, with oversight from an independent Data Monitoring Committee. The main outcomes measured include changes in annualized growth velocity at 6 months and height changes over 4 years. Follow-up assessments will continue as needed, including safety monitoring, until study completion, which could last up to 15 years.

Researchers are evaluating the effects of ALN-APP on disease progression in adults with sporadic Cerebral Amyloid Angiopathy sCAA and Dutch-type Cerebral Amyloid Angiopathy D-CAA. This Phase 2 study aims to assess the safety, tolerability, and pharmacodynamics of ALN-APP in these patient groups. The study is sponsored by Alnylam Pharmaceuticals and includes a randomized, double-blind, placebo-controlled design. Participants will receive multiple doses of ALN-APP or placebo administered intrathecally during a 24-month double-blind treatment period. Those who continue into an optional 18-month open-label extension will receive ALN-APP. The study involves two main periods the initial double-blind treatment phase followed by an optional open-label extension. During the study, participants will undergo brain MRIs to measure new cerebral microbleeds and other brain changes. Researchers will also assess cerebrovascular vasoreactivity using functional MRI and measure amyloid precursor protein levels in cerebrospinal fluid. Safety and adverse events will be monitored throughout the up to 50 months of participation, which includes screening, treatment, and safety follow-up.