Ranica

Researchers are evaluating the effects of felzartamab in adults with Immunoglobulin A nephropathy (IgAN), a kidney disease caused by the buildup of abnormal IgA antibodies in the kidneys. This buildup leads to inflammation and damage, causing protein to appear in the urine. The study aims to understand how felzartamab influences proteinuria and kidney function, while also assessing the safety and how the body processes this treatment. This is a Phase 3, randomized, double-blind, placebo-controlled study focusing on adults with IgAN. Participants will be randomly assigned to receive either felzartamab or a placebo through intravenous (IV) infusions. Neither the participants nor the researchers will know which treatment is given. The treatment period lasts 24 weeks followed by an 80-week follow-up period. In total, participants will attend 17 study visits over about 2 years to receive infusions and participate in study activities. During the study, participants will undergo assessments including urine tests to measure protein levels, kidney function evaluations, and safety monitoring. Researchers will track changes in proteinuria from the start of the study to Week 36 as the main outcome. Additional measurements will include kidney function, clinical endpoints, and the study of how felzartamab is processed by the body. Participant safety and long-term effects will be monitored throughout the study and follow-up periods.

Researchers are studying primary membranous nephropathy (PMN), an autoimmune kidney disease caused by antibody deposits on the glomerular capillary wall. This condition affects 5-10 people per million and is a leading cause of nephrotic syndrome in adults. The study focuses on tracking the disease course and long-term outcomes in real-world clinical practice, especially considering the advances in treatments like rituximab and other monoclonal antibodies that target specific immune cells involved in PMN. The study is observational and longitudinal, involving patients diagnosed with PMN and nephrotic syndrome (proteinuria >3.5 g/24 hours). Patients receive treatments such as rituximab or newer monoclonal antibodies aimed at reducing harmful antibody production. The research gathers data from routine clinical visits to understand the natural history of PMN and evaluate how these therapies affect disease progression and remission. Participants will be followed for about six months on average, during which researchers will collect data from medical records, lab tests, and clinical assessments. The main outcome measured is disease remission. Data will help identify factors predicting outcomes and treatment responses, providing valuable insights into managing PMN and improving care strategies.

Researchers are evaluating the levels of circulating anti-nephrin autoantibodies in adults with idiopathic nephrotic syndrome (INS), including those with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and patients who have experienced relapse of FSGS after kidney transplant. The study compares these patients to a control group with nephrotic syndrome caused by primary membranous nephropathy (MN). INS is a challenging kidney condition marked by proteinuria and systemic complications, with limited treatment options especially for FSGS and its recurrence post-transplant. The study uses ELISA tests, including in-house methods and commercial kits, to detect anti-nephrin autoantibodies in blood samples. Recombinant nephrin protein is coated on ELISA plates, and patient serum is tested for the presence of these antibodies by measuring absorbance after a series of antibody incubations. The analysis is retrospective, focusing on stored samples from patients with biopsy-proven diagnoses. Participants provide consent for their samples to be stored in a certified biobank. Researchers measure the levels of anti-nephrin autoantibodies at one year to compare patients with INS and controls with MN. This helps to explore the potential role of these autoantibodies as circulating factors involved in the disease process. The study monitors patients' biopsy results and clinical histories, with no intervention treatment administered as part of the research.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, where many patients have antibodies against the phospholipase A2 receptor (PLA2R). This study focuses on examining differences in immune cells, especially B-cells, between patients who respond and do not respond to B-cell depleting treatments. Researchers aim to understand how autoreactive B-cells contribute to the disease and treatment outcomes by analyzing these cells in patients and healthy volunteers over time. Participants include adults with biopsy-confirmed idiopathic MN, some of whom have received or will receive B-cell depleting therapy, as well as healthy adults without significant illnesses. The study involves collecting blood samples for biochemical and flow-cytometry tests to analyze immune cell subsets, particularly autoreactive B-cells targeting PLA2R, under resting and stimulated conditions. Throughout the study, researchers will monitor changes in immune cell frequencies and activity at multiple time points up to 24 months. They will also compare responders and non-responders to treatment and healthy controls. Participants will provide informed consent and undergo urine testing if healthy. The study assesses immune markers and clinical outcomes to identify predictors of treatment success and gain insights into MN disease mechanisms.

Researchers are investigating the use of RNA sequencing (RNA-Seq) to find genetic changes causing undiagnosed rare diseases in both children and adults who have symptoms starting early in life and who previously had negative results from whole-exome sequencing (WES). The project aims to improve diagnosis by studying RNA alterations that WES may miss, especially changes affecting gene splicing and expression. The study includes healthy volunteers, patients with known genetic diseases for validation, and undiagnosed patients suspected of having rare genetic disorders despite negative WES results. The study involves collecting skin biopsies to grow fibroblasts, which are then analyzed using RNA-Seq to detect RNA-level changes. Five healthy subjects will provide samples to develop and validate the analysis method. Ten adult patients with known genetic alterations affecting RNA serve as positive controls. The main cohort will include about 30 symptomatic patients with suspected rare diseases who had inconclusive WES results. Blood samples will also be collected for DNA and RNA studies, and plasma and serum samples will be stored for further analysis. Participants will undergo skin biopsies using a small punch procedure under local anesthesia, which takes about 15 minutes and usually leaves minimal scarring. Researchers will perform transcriptome analysis to identify RNA splicing and expression changes. They will compare RNA profiles from skin fibroblasts to those from blood and validate findings with additional tests. The study will monitor genetic and transcriptional changes and store samples in a biobank for possible future research. Overall participation involves sample collection, consent procedures, and clinical data gathering.

Researchers are investigating the effectiveness and safety of switching from anti-C5 antibody treatment to iptacopan in adults diagnosed with atypical hemolytic uremic syndrome (aHUS). This Phase 3, multicenter, single-arm, open-label study focuses on participants who have already been treated with anti-C5 antibodies and aims to assess the impact of iptacopan on aHUS symptoms and disease markers over time. Participants will first undergo a screening period lasting up to 14 weeks to confirm eligibility and clinical response to prior anti-C5 antibody treatment. Those who qualify will then enter a 12-month core treatment phase with iptacopan, followed by an additional 12-month extension period to monitor ongoing effects. Vaccinations against certain bacterial infections are required before starting iptacopan. During the study, participants will have regular assessments to monitor blood counts, kidney function, and other indicators relevant to aHUS. The main outcome measured is the percentage of participants who remain free of thrombotic microangiopathy (TMA) symptoms after 12 months. Safety and any side effects will also be closely observed throughout the treatment and extension periods, with total participation lasting up to two years.

Atypical Hemolytic Uremic Syndrome (aHUS) is a rare disease marked by the breakdown of red blood cells, low platelet count, and blockage of small blood vessels, mainly affecting the kidneys. Unlike typical HUS caused by E. coli infection, aHUS may have a genetic origin and occurs in both children and adults. This research focuses on studying genetic mutations, including those affecting the complement system and the DKGE gene, to better understand the disease mechanisms and explore personalized therapy options. Participants will provide blood and urine samples, with 10-20 ml drawn from children and 30-50 ml from adults, both patients and healthy volunteers. The study involves generating and analyzing patient-specific and healthy donor induced pluripotent stem cells (iPSC), differentiating these cells into endothelial cells, and assessing cell culture viability. Researchers will compare cells derived from aHUS patients with specific genetic mutations to control cells to identify abnormalities and potential drug treatments. Throughout the study, various tests and evaluations will be performed once per participant, including characterizing the iPSC and their endothelial cells. The study aims to monitor cellular function and viability to understand disease effects better. Informed consent is required, and the total participation duration depends on the timing of sample collection and laboratory analyses.

Researchers are evaluating the long-term effects of iptacopan (LNP023) in people with C3 glomerulopathy or idiopathic immune-complex-membranoproliferative glomerulonephritis (IC-MPGN). This open-label extension study follows participants who have completed earlier Phase 2 or Phase 3 studies to gather more data on the drug's safety, effectiveness, and tolerability over an extended period. The study supports regulatory submissions by collecting long-term information about iptacopan's impact on these kidney conditions. Participants receive open-label iptacopan capsules, continuing treatment after completing prior studies CLNP023X2202, CLNP023B12301, or CLNP023B12302. The study includes adults and adolescents with C3G or IC-MPGN and allows continued access to the medication while collecting additional safety and efficacy data. The extension may last up to approximately 168 months or until the drug becomes commercially available or if the benefit-risk balance changes. During the study, researchers monitor participants regularly for kidney function, safety labs, vital signs, ECGs, and adverse events. They measure outcomes such as composite renal endpoints, changes in kidney tissue deposits, and incidence of safety concerns over 6 to 9 months and longer. Participants are expected to continue in the study from a minimum of 60 months up to 84 months or more, with ongoing assessments to support long-term safety and efficacy profiles of iptacopan.

Researchers are conducting a single-center observational study to develop and test new advanced ultrasound imaging protocols for vascular health. The study focuses on capturing detailed ultrasound images of blood vessels in the non-dominant arm and neck areas, aiming to establish normal reference values, assess measurement consistency, and explore how age and gender relate to these ultrasound parameters. This work supports better understanding of vascular changes related to renal and cerebral diseases. Participants will undergo ultrasound examinations using a state-of-the-art Resona 9 ultrasound machine equipped with advanced imaging features, including three-dimensional tomographic capabilities. The study will perform ultrasound scans of the non-dominant arm and both sides of the neck to capture detailed vascular images. After the initial examination, participants may be asked to consent to further follow-up scans if necessary. During the study, participants will be assessed through ultrasound imaging to collect data on vascular wall thickness, stiffness, and blood flow patterns. Researchers will analyze these images to determine normal ranges and repeatability of measurements. The study involves 60 subjects aged 18 to 75 years without prior kidney or cerebral diseases. Participants will provide informed consent and may undergo future ultrasound scans depending on study needs.

Researchers are evaluating the effectiveness of ALXN1920 compared to a placebo in adults with Primary Membranous Nephropathy (PMN) who have a high risk of disease progression. This Phase 2a study focuses on changes in protein levels in urine, measured by the 24-hour urine protein creatinine ratio (UPCR), to assess treatment impact over 26 weeks. Participants will be randomly assigned to receive either ALXN1920 or a placebo through subcutaneous infusion. Both groups will continue to receive their standard care, including ACE inhibitors or ARBs, which must be optimized before the study begins. The study is double-blind and conducted at multiple centers to ensure rigorous evaluation. Throughout the study, participants will undergo regular assessments including urine protein measurements at baseline and week 26. Safety, tolerability, and immune responses will also be monitored. The study includes careful screening and follow-up procedures to track kidney function and other health indicators during the treatment period.