62 Clinical Trials for Various Conditions
This study will evaluate the safety and effectiveness of the experimental drug eculizumab for treating paroxysmal nocturnal hemoglobinuria (PNH), a disorder that can cause premature destruction of red blood cells. PNH may result in anemia requiring blood transfusions. Patients may be at high risk of life-threatening blood clots in their veins and may have urine discoloration, stomach pain, difficulty swallowing, tiredness, and poor quality of life. Men may have problems getting or maintaining an erection. Eculizumab is a monoclonal antibody that may improve the survival of red blood cells in patients with PNH. Patients 18 years of age and older who have been diagnosed with PNH for more than 6 months, who have active disease, and who require blood transfusions may be eligible for this study. Each candidate is screened with a physical examination, electrocardiogram, blood and urine tests, and a questionnaire for information on how PNH affects the patient physically, socially, emotionally, and functionally. Participants receive infusions of eculizumab through a needle in a vein once a week for five doses and then every two weeks for another 24 doses. All patients are vaccinated against Neisseria meningitides, a bacteria that can cause symptoms, possibly including life-threatening meningitis, in susceptible people, including people who take eculizumab. At every treatment visit, patients update their health status, transfusion record, and medication use; review their laboratory results from the preceding visit; have vital signs measured; and provide a blood sample for laboratory tests. At selected visits, they also provide a urine sample, have a repeat electrocardiogram, and complete a questionnaire. At the final treatment visit, participants have a complete physical examination, in addition to the routine procedures.
The purpose of this study is to evaluate the long-term safety of eculizumab in patients with transfusion dependent hemolytic PNH.
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including graft versus host disease (GVHD) and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. This research project will investigate the use of particular pre-transplant conditioning regimen (chemotherapy, antibodies and total body irradiation) followed by a stem cell infusion from a "mismatched" family member donor. Once these stem cells are obtained they will be highly purified in an effort to remove T cells using the investigational CliniMACS stem cell selection device. The primary goal of this study will be to determine the rate of neutrophil and platelet engraftment, as well as the degree and rate of immune reconstitution in the first 100 days posttransplant for patients who receive this study treatment. Researchers will also study ways to decrease complications that may occur with a transplant from a genetically mismatched family donor.
OBJECTIVES: I. Confirm the efficacy demonstrated in a pilot study using high dose cyclophosphamide in patients with severe aplastic anemia. II. Determine whether the addition of filgrastim (G-CSF) to high dose cyclophosphamide shortens the time to recovery in these patients. III. Determine whether this regimen is efficacious in treating paroxysmal nocturnal hemoglobinuria.
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 primary objective of the study is: To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy The secondary objectives of the study are to: * Evaluate the effect of pozelimab and cemdisiran combination treatment versus anti-C5 standard-of-care treatment (eculizumab or ravulizumab) on the following: * Transfusion requirements and transfusion parameters * Measures of hemolysis: LDH control, breakthrough hemolysis, and inhibition of CH50 * Hemoglobin levels * Fatigue as assessed by Clinical Outcome Assessments (COAs) * Health-related quality of life (HRQoL) as assessed by COAs * Safety and tolerability * To assess the concentrations of total pozelimab and either total eculizumab or total ravulizumab in serum and total cemdisiran and total C5 protein in plasma * To assess the immunogenicity of pozelimab and cemdisiran
The purpose of this study is to evaluate the safety, effectiveness, and biological activity (how the investigational medication is processed by the body) of pegcetacoplan in 12-17 year-olds (adolescents) who have paroxysmal nocturnal hemoglobinuria (PNH).
This study is an open-label, single arm, multicenter, roll-over extension study to characterize long-term safety, tolerability and efficacy of iptacopan and to provide access to iptacopan to patients with PNH who have completed Novartis-sponsored Phase 2 or 3 studies with iptacopan
The main objective of this study is to evaluate the efficacy of danicopan as add-on therapy to a complement component 5 (C5) inhibitor (eculizumab or ravulizumab) in participants with PNH who have clinically evident EVH.
A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.
The primary objective of this study is to evaluate pharmacokinetics (PK) of ravulizumab administered subcutaneously via an on-body delivery system (OBDS) compared with intravenously administered ravulizumab in adult participants with PNH who are clinically stable on eculizumab for at least 3 months prior to study entry.
Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria
To determine the effectiveness of ACH-0144471 (also known as danicopan and ALXN2040) in improving anemia when given with eculizumab for 24 weeks in participants with PNH. Danicopan dose may be increased within each participant, to a maximum of 200 milligrams (mg) three times daily (TID) based on safety and efficacy at protocol-specified time points.
The purpose of this study was to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ravulizumab in pediatric participants with paroxysmal nocturnal hemoglobinuria (PNH).
The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who were clinically stable after having been treated with eculizumab for at least 6 months.
The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who had never been treated with a complement inhibitor (treatment-naïve).
How does long term treatment with Soliris affect HAHA in PNH patients?
This study is a collection of data to evaluate safety and characterize progression of Paroxysmal Nocturnal Hemoglobinuria (PNH).
The purpose of this research study is to understand the safety, pharmacokinetics and pharmacodynamics of a single dose of TT30 (ALXN1102 and ALXN1103 formulations) when given IV (through a vein) or SC (under the skin) to patients with PNH.
The purpose of this study is to examine how abnormal blood flow in the small vessels (microvessels) of the heart, muscle and kidney in paroxysmal nocturnal hemoglobinuria (PNH) or sickle cell disease leads to poor functioning of the heart and kidney. To test this question, the investigators will perform imaging tests (contrast ultrasound perfusion imaging) to look at the flow and function of these microvessels and compare this information to heart and kidney function. To further look at this question, patients who have PNH will be studied before and after starting a new drug (Soliris) that decreases damage to blood cells. In patients with sickle cell disease, patients will be studied at baseline (not during a pain crisis) and also during a pain crisis if one develops.
The primary objective of this study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) parameter estimates of eculizumab to confirm the dose regimens for pediatric and adolescent participants with PNH.
This study is designed to better understand the molecular biology of paroxysmal nocturnal hemoglobinuria (PNH) and to determine if prion protein (PrP) functions in long term hematopoietic stem cell renewal.
The primary objective is to provide access to eculizumab for PNH patient pending commercial availability.
The primary objective is to evaluate the safety and efficacy of eculizumab in transfusion dependent patients with hemolytic PNH.
The primary objective is to evaluate the safety of eculizumab in patients with transfusion-dependent hemolytic PNH
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of eculizumab may prevent leukemia and stop the destruction of red blood cells in patients with paroxysmal nocturnal hemoglobinuria. PURPOSE: This randomized phase III trial is studying how well eculizumab works in treating patients with paroxysmal nocturnal hemoglobinuria.
This study will examine the safety and effectiveness of the experimental drug eculizumab in treating patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare disorder of red blood cells that leads to premature destruction of the cells and resulting anemia. Patients may be at high risk of blood clots and may develop bone marrow failure or aplastic anemia, with low white blood cell and platelet counts. Eculizumab is a monoclonal antibody that may help improve the survival of red blood cells. Patients 18 years of age and older with PNH who require blood transfusions for anemia and have received at least four transfusions in the 12 months preceding evaluation for this study may be eligible to enroll. Candidates are screened with a medical history, physical examination, and check of vital signs. Participants have an electrocardiogram (EKG) and blood and urine tests, and are vaccinated against Neisseria meningitides, a common bacteria that can cause a disabling or fatal type of meningitis. They then enter an observation phase of the study, with monthly visits during which they complete a questionnaire; update their health status, transfusion record, and medication use; have their vital signs checked and PNH symptoms evaluated; have blood and urine tests; and receive a transfusion, if necessary. These visits continue for up to 3 months until patients receive a "qualifying" transfusion; that is, a transfusion given as a consequence of a certain hemoglobin level with symptoms or a different level without symptoms. Patients are then randomly assigned to receive either eculizumab or a placebo (salt solution with no active ingredient). Both study medications are given intravenously (through a vein) over 30 minutes once a week for five doses and then once every 2 weeks for another 11 doses. At each treatment visit (study weeks 0-24), patients update their health status, transfusion records, and medication use; have their vital signs checked; and provide a blood sample. At various visits, they also complete a questionnaire, provide a urine sample and have an EKG. At the last treatment visit (week 26 or the final visit for patients who end their participation before visit 18) patients have a complete physical examination in addition to the procedures listed above.
This study will examine blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) after they receive a blood transfusion to determine if certain proteins (GPI-linked proteins) in the transfused blood transfer to the patient's blood cells. GPI-linked proteins, which are normally present on red cells and regulate red cell survival, are absent in patients with PNH. Their lack is believed to account for the premature destruction of red blood cells in these patients, resulting in a low hemoglobin and hematocrit. Patients may experience fatigue, flank pain and other symptoms, requiring treatment with blood transfusion. Patients with PNH 18 years of age or older with group A1 blood who require at least three units of red cells and who have not been transfused with group O blood within the last 3 months may be eligible for this study. Participants will come to the NIH Clinical Center for the following procedures: * Interview about the severity of their anemia-related symptoms * Blood test * Blood transfusion, if required. Patients will be transfused with compatible group O blood. The donor blood will be washed (rinsed with a salt solution) until it is 99% free of donor plasma. Group O blood is given instead of group A1 in order to be able to distinguish the patient's cells from the transfused cells. Blood samples of 3 teaspoons each will be drawn 1 day, 1 week, and 3 weeks after the transfusion. These samples may be collected by the patient's doctor locally and sent to NIH by mail. If it is found that GPI-linked proteins transfer to the patient's cells, the study will also examine how long the proteins remain attached and will assess whether the proteins are functional and prevent cell destruction.
The aim of this International PNH Interest Group (IPIG) registry is to develop an international database to prospectively collect data on patients with PNH covering clinical outcomes, patient reported outcomes (PROs), and health-resource utilization (HRU) on all enrolled patients, as well as long term safety data.