Paroxysmal Nocturnal Hemoglobinuria (PNH)

The protocol will be amended to describe Part B of the study after Part A data have been analyzed.

The implementation of new standards for the management of PNH and the use of iptacopan in patients with PNH are expected to change the treatment landscape and improve the overall prognosis of patients. Based on these backgrounds, we plan to conduct a real-world study of iptacopan to further evaluate its impact on treatment-related outcomes, disease management, and healthcare resource utilization in Chinese patients with PNH.

As pegcetacoplan is a new product on the market, with a new mechanism of action, there is an urgent need to provide data to treaters, payers and the PNH community on the real-world usage and effectiveness of pegcetacoplan. This study aims to fill part of that knowledge gap and to add to the knowledge base regarding the use of pegcetacoplan in routine medical practice. Another important rationale for this study is to provide information on RBC transfusions and health care resource utilization pre and post pegcetacoplan treatment initiation. The study plans to include approximately 200 patients at 70 sites in Europe, Middle East, Canada and Australia. Additional countries may be added in the study if necessary. Patients meeting the eligibility criteria will be enrolled in the study and followed prospectively for approximately 36 months. Patient data will be collected from start of pegcetacoplan treatment to end of follow-up. Retrospective data on pegcetacoplan will be captured from the time of pegcetacoplan treatment initiation. Pegcetacoplan treatment data will be collected for a minimum of approximately 36 months and up to a maximum of approximately 72 months, including retrospective period depending on when the patient started pegcetacoplan treatment. After pegcetacoplan treatment discontinuation, patients will remain in the study for 8 weeks to capture any AEs. Patients will come to their routine visits and the available data from each visit will be collected. The scope of the study is to collect both retrospective and prospective data. The main part of the study will be prospective, collecting data on effectiveness, safety, patient- and clinician-reported outcomes and health care resource use. The study will also collect retrospective data before pegcetacoplan treatment start, which will consist of information on PNH treatment, blood transfusions and healthcare resource use. Data will be collected for up to 12 months prior to pegcetacoplan treatment start. As patients may have been treated with pegcetacoplan for up to 12 months prior to enrollment, retrospective data may be collected for up to 24 months. This means that the total data collection period including both the retrospective and the prospective part is up to 48 (+/- 3) months.

This study is researching an experimental treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of this study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH in the long term. The pozelimab + cemdisiran combination may be referred to as "study drugs" in this section. This study is looking at several other research questions, including: * How effective is the pozelimab + cemdisiran combination? * What side effects may happen from taking the study drugs? * How much of each study drug is in the blood at different times? * Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects)

This is an open-label study to evaluate pegcetacoplan in people with PNH who are 12-17 years old. The study will consist of a 4-week screening period followed by a 16-week treatment period. Participants switching from a C5 inhibitor will have an additional 4 week run-in period between the screening and treatment periods. At the completion of the study treatment period, participants will either enter a long-term extension period or a 2-month follow-up period. All eligible study participants will receive pegcetacoplan, administered via subcutaneous infusion twice a week at home. The subcutaneous infusion requires two small needles to be inserted into the fatty layer of tissue under the skin and the investigational medication will flow into the body. Study participants and/or caregivers will be trained on home administration of pegcetacoplan.

The treatment period has two parts, a Treatment Period (TP, 28 weeks) and an Extension treatment Period (EP, 52 weeks).

This study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH and how the combination compares with 2 existing treatments: ravulizumab and eculizumab. The pozelimab + cemdisiran combination may be referred to as "study drugs". Ravulizumab and eculizumab may also be called the "comparator drug". The study is looking at several research questions, including: * How effective is the pozelimab + cemdisiran combination compared to ravulizumab? * How effective is pozelimab + cemdisiran combination compared to eculizumab? * What side effects may happen from taking the study drugs? * How much study drugs are in the blood at different times? * Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)

The study is designed to assess the feasibility and performance of the ABL90 FLEX PLUS HEM device in a clinical environment. It will involve testing whole blood samples using the device and comparing results against established reference method. The primary focus is on validating the device's performance of the hemolysis detection function. The study will be conducted at one selected clinical site with trained personnel and will follow a predefined protocol to ensure consistency and reliability of data collection. The outcomes will inform future clinical studies aimed at supporting regulatory submissions and clinical adoption.

The Global PNH Patient Registry is a prospective, longitudinal, web-based, observational natural history study. Participants with PNH will be followed throughout the course of their lives with either the participant or authorized respondents contributing data at varying intervals throughout the course of the study. Data will be collected at the start of the study (baseline), at least once per year or can be updated by the participant as needed. Data will be collected on demographics, quality of life, medical history, disease phenotypes, disease-related events, personal experience with PNH, general health status, medications, and diagnoses. The Global PNH Patient Registry provides a convenient online platform for participants; facilitates communication about PNH; gives researchers the ability to characterize the PNH population as a whole; assists the PNH community with the development of recommendations and standards of care and; and serves as a case-finding resource to be used for researchers to study the pathophysiology of PNH. A Registry Advisory Board, that may include scientists, doctors, and patient advocates, will be assembled to oversee the conduct of the study. The Advisory Board will review aggregate registry data and the use of this registry, ensure proper evaluation of protocols requesting to use registry data and/or contact registry participants, and review any protocol or confidentiality deviations on a case- by by-case basis and ensure that any such deviations are reported to the IRB. The registry will use a web-based interface to maximize accessibility to participants and clinicians world-wide. Following informed consent, participants will be invited to enter their data and information which will be stored indefinitely or until a participant revokes their consent to participate in the study. No experimental intervention is involved in participation in the Global PNH Patient registry study. Annual maintenance will be funded by the Aplastic Anemia and MDS International Foundation (AAMDSIF) with support from industry partners. Registry participants will be automatically enrolled in NORD's Natural History Study Program (NHS), and their de-identified information aggregated with information from other rare diseases may be used for the purposes of cross disease analysis and cross-disease research to facilitate advocacy and further NORD's mission. De-identified information may be shared with other databases such as the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP). This will allow more researchers to use the information to do research.

Severe aplastic anemia (SAA),myelodysplastic syndrome (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) are life-threatening bone marrow disorders. For SAA patients, long term survival can be achieved with immunosuppressive treatment. However, of those patients treated with immunosuppressive therapy, one quarter to one third will not respond, and about 50% of responders will relapse. Although allogeneic stem cell transplantation (allo-SCT) offers the opportunity of cure, HLA-matched donors are available for only half the patients needing a transplant. Combined haplo-cord transplantation has recently been shown to be a viable transplant option for those patients lacking an HLA matched donor. In our ongoing protocol 08-H-0046, we have utilized this approach in 29 patients with SAA, and SAA evolving to MDS with 27/29 patients having sustained engraftment and achieving transfusion independence. However, engraftment patterns have varied substantially and, in some patients,, cord engraftment was profoundly delayed or never occurred. Haploidentical peripheral blood stem cell transplantation (haplo-SCT) has the advantage over cord transplantation of immediate allograft availability, higher stem cell doses, and the feasibility of repeating cell collections if necessary for collecting CD34+ cells for stem cells boosts or lymphocytes to treat or prevent disease relapse or infection. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but most reports have focused on patients with hematological malignancies. At present, few data exist on the use of haploidentical transplantation using post-transplant cyclophosphamide for patients with aplastic anemia that have ATG-refractory disease and are heavily-transfused and HLA-alloimmunized. These patients are at an exceedingly high-risk for graft rejection compared to other patient populations. This research protocol is therefore designed to evaluate the safety and effectiveness of using an unmanipulated GCSF mobilized peripheral stem cell allograft from a haploidentical donor and post-transplant cyclophosphamide for patients with SAA,SAA evolving to MDS, or PNH that has proven to be refractory to conventional therapy in patients who lack an HLA-matched donor (sibling/ or matched unrelated donor). The primary endpoint of the study is chronic GVHD-free survival (defined as the percentage of patients who are alive with no evidence of moderate or severe chronic GVHD at 1-year post-transplant). Secondary endpoints will include engraftment, 100 day and 200-day treatment related mortality (TRM), and standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD, and relapse of disease. Health related quality of life will also be assessed as secondary outcome measure.