Paroxysmal Nocturnal Hemoglobinuria (PNH)

Researchers are evaluating an experimental drug called ALN-CFB in adults with Paroxysmal Nocturnal Hemoglobinuria (PNH) who continue to have anemia despite treatment with a complement component C5 inhibitor. This Phase 1 and 2 study aims to assess the safety and tolerability of ALN-CFB compared to a placebo, while also examining how the drug affects levels of Complement Factor B (CFB) protein in the blood and its concentration over time. Participants will be randomly assigned to receive either ALN-CFB or a placebo following a single-ascending dose escalation design. The study includes a double-blind period where neither participants nor researchers know who receives the drug or placebo. The protocol will be updated to describe Part B after analysis of Part A data. During the study, participants will be monitored for treatment-emergent adverse events and their severity over one year. Researchers will measure ALN-CFB and its metabolites in plasma and urine, along with changes in CFB concentration from baseline. The study involves regular visits for assessments and safety monitoring, lasting up to 365 days.

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 iptacopan's real-world impact on disease and quality of life.

Researchers are observing the real-world use and effects of pegcetacoplan in adults with Paroxysmal Nocturnal Hemoglobinuria (PNH). This long-term study aims to provide important information on how pegcetacoplan is used in routine medical practice and to understand its impact on blood transfusions and healthcare resource use. Approximately 200 patients will participate at various sites across Europe, the Middle East, Canada, and Australia. Pegcetacoplan treatment data will be collected both retrospectively and prospectively, covering up to 72 months depending on when treatment began. After patients stop pegcetacoplan, they will be followed for an additional 8 weeks to monitor any adverse events. Patient data includes effectiveness, safety, patient- and clinician-reported outcomes, and healthcare resource use before and after treatment. Participants will attend their regular medical visits where data will be collected. Researchers will monitor changes in hemoglobin levels and other blood markers every 6 months. They will also track adverse events and patient satisfaction. The total participation may last up to 48 months, including both retrospective and prospective data collection periods.

Researchers are studying an experimental combination of two drugs, pozelimab and cemdisiran, to evaluate their long-term safety and effectiveness in adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder. The study aims to understand how well this combination controls the disease, what side effects may occur, how the drugs behave in the body, and whether the body develops antibodies against them. The study includes two groups: patients who completed treatment in a previous related study and patients with PNH who have a specific genetic variation making them resistant to other treatments. Participants receive the combination therapy, with a loading dose of pozelimab given intravenously on the first day. The study is open-label and non-randomized, focusing on long-term treatment effects and safety. Participants will attend regular clinic visits for up to 108 weeks, where researchers will monitor adverse events, blood levels of the drugs, disease activity markers like lactate dehydrogenase (LDH), and symptom changes. They will also track transfusion needs, hemoglobin stability, fatigue, physical function, and quality of life using questionnaires. Safety assessments include monitoring serious adverse events and immune responses to the drugs throughout the study period.

Researchers are evaluating pegcetacoplan, a complement (C3) inhibitor, in adolescents aged 12 to 17 years with paroxysmal nocturnal hemoglobinuria (PNH). The study aims to assess the safety, effectiveness, and how the medication is processed by the body in this younger population. This open-label phase 2 trial is sponsored by Apellis Pharmaceuticals, Inc. and focuses on understanding pegcetacoplan's biological activity and impact on hemoglobin and other blood markers. The study includes a 4-week screening period, followed by a 16-week treatment period where all participants receive pegcetacoplan via subcutaneous infusion twice weekly at home. Those switching from a C5 inhibitor will have an additional 4-week run-in period before treatment. After the treatment period, participants may continue in a long-term extension or enter a 2-month follow-up phase. Participants and caregivers are trained on how to administer the medication at home using two small needles. During the study, participants will have regular assessments including blood tests to measure hemoglobin, lactate dehydrogenase, reticulocyte count, and pegcetacoplan blood levels. Researchers will monitor adverse events, infections, and other safety concerns throughout the 16-week treatment. Longer-term effects will be evaluated during extension or follow-up periods. The study also includes quality of life assessments and tracks the need for blood transfusions. Total participation time varies depending on extension or follow-up enrollment.

Researchers are studying a combination treatment using two experimental drugs, pozelimab and cemdisiran, for adults with Paroxysmal Nocturnal Hemoglobinuria (PNH) whose condition has not been well controlled by current treatments with complement component 5 (C5) inhibitors like eculizumab, ravulizumab, or crovalimab. The study aims to evaluate how effectively this combination reduces hemolysis and to investigate side effects, blood drug levels, and the body's antibody response to the drugs. The treatment period includes two parts: an initial 28-week Treatment Period (TP) followed by a 52-week Extension Period (EP). Participants receive the combination therapy of pozelimab and cemdisiran administered according to the study protocol. The study monitors the drugs' effects and safety throughout both treatment phases to assess the overall impact on controlling hemolysis. During the study, participants will attend clinic or remote visits for assessments including blood tests to measure lactate dehydrogenase (LDH) levels and hemoglobin, monitoring of fatigue, adverse events, and antibody development against the study drugs. The main outcome measured is the percent change in LDH from baseline to week 28, with ongoing evaluations through week 52. Participants must stay up to date with meningococcal vaccinations and comply with study procedures throughout the trial, which continues until November 2031.

Researchers are evaluating the safety and effectiveness of Danicopan as an add-on treatment to C5 inhibitors (Eculizumab or Ravulizumab) in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) in Korea. This observational study aims to monitor known safety profiles and detect any unexpected adverse reactions in real-world clinical settings. It also seeks to assess how well Danicopan works when used alongside these existing therapies in routine medical practice. Participants in this study are patients prescribed Danicopan as an additional therapy to either Eculizumab or Ravulizumab under approved indications in Korea. The study focuses on treatment safety and effectiveness over a 12-week period. There is no experimental intervention assignment since this is an observational post-marketing study conducted under normal clinical conditions. During the study, safety data such as adverse events, serious adverse events, and drug reactions will be collected for up to 12 weeks from the first dose of Danicopan. Effectiveness will be evaluated through changes in hemoglobin levels, reticulocyte counts, fatigue scores, and the proportion of patients avoiding red blood cell transfusions at 12 weeks or at treatment end if earlier. Participants will receive routine clinical assessments without additional experimental procedures.

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 device's 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 device's 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.

This research investigates the safety and effectiveness of using peripheral blood hematopoietic stem cells from a family member combined with chemotherapy to treat severe aplastic anemia (SAA), hypoplastic myelodysplastic syndrome (MDS), and paroxysmal nocturnal hemoglobinuria (PNH). These serious bone marrow disorders often require stem cell transplants, and the study aims to evaluate whether peripheral blood stem cells (PBSCs) are a good alternative to bone marrow cells, especially for patients without an HLA-matched donor. The study also assesses post-transplant cyclophosphamide as a method to prevent graft-versus-host disease (GVHD). Participants receive stem cells mobilized by G-CSF injections from a haploidentical donor, followed by chemotherapy over eight days and a single radiation treatment. The transplant procedure includes inserting a central line, administering medicines for side effects, and infusing stem cells over about four hours. Donors undergo blood and tissue tests, receive injections to boost stem cell production, and donate blood stem cells collected through a machine that separates the needed cells before returning the rest to the donor. Recipients stay in the hospital for approximately one month after transplant and are monitored weekly for up to six months near NIH with physical exams and blood tests. After day 180, participants return home but continue follow-up visits at their doctor’s office and NIH multiple times over five years. The primary study outcome is survival without moderate or severe chronic GVHD at one year, with other measures including transplant success, treatment-related mortality, disease relapse, and quality of life.