Paroxysmal Nocturnal Hemoglobinuria (PNH)

Researchers are studying an experimental drug called ALN-CFB for adults with Paroxysmal Nocturnal Hemoglobinuria PNH who continue to have anemia despite treatment with a complement component C5 inhibitor. This study aims to evaluate the safety, tolerability, and initial effectiveness of ALN-CFB compared to a placebo. The study also examines how ALN-CFB affects levels of Complement Factor B protein in the blood and how the drug is processed in the body. Participants will receive either ALN-CFB or a placebo in a randomized, double-blind manner. The study includes a single-ascending dose escalation design to find the appropriate dosing. The protocol will be updated after initial data analysis to describe further parts of the study. Treatment duration and dosing schedules are defined by the study protocol. During the study, participants will undergo regular evaluations including blood tests to measure drug levels and Complement Factor B concentrations, and will be monitored for side effects for up to 365 days. Researchers will assess the occurrence and severity of treatment-emergent adverse events. The study spans several years, with the primary completion expected in late 2029 and final completion by mid-2031.

Researchers are conducting a real-world study to evaluate the impact of iptacopan on adult patients with paroxysmal nocturnal hemoglobinuria PNH in China. The study aims to assess treatment-related outcomes, disease management, and healthcare resource use, considering new standards for PNH care and the introduction of iptacopan. It includes patients who are either new to complement inhibitor therapy or those stable on C5 complement inhibitors like eculizumab. The study involves two patient groups one with PNH patients never treated with complement inhibitors who are starting iptacopan, and another with patients stable on C5 complement inhibitors who will switch to iptacopan after its approval in China. Treatments are oral capsules of LNP023 iptacopan, and patients must start iptacopan within 60 days of consenting. Participants must have documented vaccinations against Neisseria meningitidis and Streptococcus pneumoniae before starting treatment. Participants will be followed for at least 12 months, with assessments including hemoglobin levels, lactate dehydrogenase LDH, absolute reticulocyte count ARC, bilirubin, PNH clone size, and signs or symptoms related to PNH. Researchers will monitor treatment effects, adverse events, medication use, transfusions, and healthcare visits. Patient fatigue and work productivity will be evaluated using specific questionnaires, with data collected at baseline and regular intervals to understand iptacopans real-world impact on disease and quality of life.

This research aims to observe the real-world use and effects of pegcetacoplan in adults diagnosed with Paroxysmal Nocturnal Hemoglobinuria PNH. As a new treatment with a unique mechanism of action, pegcetacoplans effectiveness and safety in routine medical practice are being studied to provide valuable information for patients, healthcare providers, and payers. The study will also gather data on blood transfusions and healthcare resource use before and after starting pegcetacoplan. Patients who have started pegcetacoplan treatment within the past 12 months or are prescribed the drug at enrollment will be included. Data collection includes retrospective information from up to 12 months before treatment start and prospective monitoring for approximately 36 months, with the total data period extending up to about 48 months. After stopping pegcetacoplan, patients remain in the study for 8 weeks to record any adverse events. Patients continue regular clinic visits, where data from each visit will be gathered. Participants will have data collected on various health measures such as hemoglobin levels, blood markers, transfusion needs, and patient and physician treatment satisfaction at regular intervals up to 36 months. Safety and adverse events will be monitored throughout. The main outcome measured is the change in hemoglobin level from treatment start to 6 months. This long-term observational study allows for comprehensive tracking of pegcetacoplans use and effects over time in usual care settings.

Researchers are studying an experimental treatment combining two drugs, pozelimab and cemdisiran, to evaluate their long-term safety and effectiveness for adults with paroxysmal nocturnal hemoglobinuria PNH. This Phase 3 study aims to answer key questions about how well this combination works, potential side effects, drug levels in the blood, and whether the body develops antibodies against the drugs that could affect treatment. Participants include those who have completed treatment in a related parent study and those with a specific C5 genetic variation making them resistant to other treatments. The study involves administering the study drugs per protocol, including a loading dose of pozelimab given intravenously on Day 1 for some participants. The study is open-label and non-randomized, with two groups based on prior treatment history or genetic markers. During the study, participants will attend clinic visits to receive treatments and undergo various assessments such as blood tests to monitor hemolysis and hemoglobin levels, measure drug concentrations, and check for antibodies. Researchers will track serious and other adverse events, treatment discontinuation, and changes in quality of life. The study lasts up to around 108 weeks, with ongoing safety and effectiveness monitoring throughout this period.

Researchers are conducting a post-marketing surveillance study in South Korea to evaluate the safety and effectiveness of iptacopan for treating patients diagnosed with either Paroxysmal Nocturnal Hemoglobinuria PNH or C3 Glomerulopathy C3G. The study collects real-world data from medical records of Korean patients receiving iptacopan under routine clinical care as part of the Risk Management Plan. This observational study aims to understand how iptacopan performs in everyday treatment settings for these conditions. Participants include adults diagnosed with PNH or C3G who have received or will receive iptacopan according to the approved Korean labeling. The study monitors two patient groups those treated for PNH and those treated for C3G. Patients must have received recommended vaccinations before starting iptacopan. Treatment is not assigned by the study but follows routine medical practice, and all dosing and administration decisions are made by the treating physicians. During the study, researchers collect data on adverse events and drug reactions over up to two years. Laboratory measurements such as hemoglobin, lactate dehydrogenase, blood cell counts, kidney function tests, and urine protein levels are collected at the start and at 24 weeks to assess changes. Investigators also evaluate overall patient improvement at 24 weeks. Participants provide informed consent, and their health information from medical records is used to assess treatment outcomes and safety in routine clinical care.

Researchers are evaluating the safety, effectiveness, and biological activity of pegcetacoplan in adolescents aged 12 to 17 years who have paroxysmal nocturnal hemoglobinuria PNH, a rare blood disorder. This open-label phase 2 study aims to understand how this investigational medication is processed by the body and its impact on PNH symptoms in this pediatric population. Participants will receive pegcetacoplan, a complement C3 inhibitor, administered as a subcutaneous infusion twice a week at home using two small needles inserted under the skin. The study includes a 4-week screening period, followed by a 16-week treatment period. Those switching from a C5 inhibitor treatment will have an additional 4-week run-in period before treatment. After the treatment period, participants may enter a long-term extension phase or a 2-month follow-up period. During the study, participants andor their caregivers will be trained to administer the medication at home. Researchers will monitor blood levels of pegcetacoplan, hemoglobin, lactate dehydrogenase, and reticulocyte counts, as well as track any treatment-emergent adverse events including infections and thromboembolic events. Quality of life and blood transfusion needs will also be assessed throughout treatment and follow-up. Overall participation may last up to 52 weeks, including the long-term extension.

Researchers are studying a combination of two experimental drugs, pozelimab and cemdisiran, to find better treatment options for adults with Paroxysmal Nocturnal Hemoglobinuria PNH whose condition has not improved despite current treatments with complement component 5 C5 inhibitors like eculizumab, ravulizumab, or crovalimab. This Phase 3 study aims to evaluate how well the drug combination lowers hemolysis and to monitor potential side effects, drug levels in the blood, and antibody responses against the study drugs. The treatment involves two periods a 28-week initial Treatment Period TP and a 52-week Extension Period EP. Participants receive the pozelimab and cemdisiran combination therapy according to the study protocol during these times. The study is designed as a single-group trial where all participants receive this combination treatment. Participants will be involved in regular clinic or remote visits throughout the study to monitor their health and treatment effects. Assessments include measuring lactate dehydrogenase LDH levels to track hemolysis, monitoring hemoglobin levels, fatigue, and transfusion needs, as well as checking for adverse events and antibody development against the drugs. The study also measures drug concentrations and complement activity. The total participation duration spans up to 80 weeks, including both treatment periods.

This research aims to assess the safety and effectiveness of Danicopan when added to C5 inhibitors Eculizumab or Ravulizumab in patients with Paroxysmal Nocturnal Hemoglobinuria PNH in Korea. It is conducted as a post-approval commitment to characterize the known safety profile and detect any unexpected adverse reactions in routine clinical practice. Participants will receive Danicopan as an add-on therapy to their existing treatment with either Eculizumab or Ravulizumab. The study observes patients under normal medical care conditions without altering their treatment plans. Data on safety will be collected for up to 12 weeks from the first dose, and effectiveness will be evaluated at 12 weeks or at the end of treatment if discontinued earlier. During the study, participants will be monitored for adverse events, serious adverse events, and other safety concerns. Effectiveness assessments include changes in hemoglobin levels, reticulocyte counts, fatigue scores, and the proportion of patients avoiding red blood cell transfusions. The total participation duration is up to 12 weeks, with data gathered from routine clinical visits and patient records.

Researchers are evaluating the ABL90 FLEX PLUS HEM device for its ability to detect hemolysis in blood samples within a clinical setting. The study focuses on assessing the devices analytical performance, particularly the hemolysis detection feature, by comparing its results to established reference methods. This feasibility performance study aims to gather data that will support future clinical trials and regulatory approval processes. The study involves testing whole blood samples from adults admitted to the hospital, many of whom are critically ill and may be unconscious or sedated. Blood samples are collected as part of standard care, often through existing arterial or venous lines, without adding extra burden to the patient. The devices hemolysis detection function is being assessed during these routine blood collections at a single clinical site with trained personnel following a strict protocol. Participants will have their blood samples analyzed once per session to measure hemolysis levels, with outcomes including the percentage of samples correctly classified into hemolysis categories. Additional measurements include changes in hemoglobin concentration over time and correlations with established hemolysis indices and potassium levels. The study ensures informed consent from participants or their legal representatives and monitors safety by excluding those for whom sample collection poses unnecessary risk. The total study duration and participant involvement are aligned with routine hospital care procedures.

Researchers are conducting the Global Paroxysmal Nocturnal Hemoglobinuria PNH Patient Registry to better understand the natural history, progression, and characteristics of PNH over time. This observational study aims to gather comprehensive data on the disease to support recommendations, standards of care, and future research, including clinical trials of new treatments. The registry also provides a platform for participants or caregivers to self-report PNH cases and facilitates communication within the PNH community. Participants with PNH will be followed prospectively through a web-based platform that allows them or authorized respondents to contribute information at varying intervals, at least once per year or as needed. Data collected includes demographics, quality of life, medical history, disease phenotypes, disease-related events, medications, and general health status. The study is overseen by a Registry Advisory Board to ensure proper conduct and data use. During the study, participants will provide data online, which will be stored indefinitely unless consent is withdrawn. Researchers will use this information to characterize the global PNH population and support further research and advocacy efforts. There is no experimental treatment involved, and participant data may be shared in de-identified form with related rare disease databases for cross-disease research. The study will continue for several years, with ongoing data collection and communication development.