Active clinical trials for "Thalassemia"

Study A536-06 is an open-label extension study for patients previously enrolled in study A536-04 (ClinicalTrials.gov Identifier NCT01749540), to evaluate the long-term safety and tolerability of ACE-536 in adult patients with beta-thalassemia.

This is a single-arm, multi-site, single-dose, Phase 1/2 study to assess ST-400 in 6 subjects with transfusion-dependent β-thalassemia (TDT) who are ≥18 and ≤40 years of age. ST-400 is a type of investigational therapy that consists of gene edited cells. ST-400 is composed of the patient's own blood stem cells which are genetically modified in the laboratory using Sangamo's zinc finger nuclease (ZFN) technology to disrupt a precise and specific sequence of the enhancer of the BCL11A gene (which normally suppresses fetal hemoglobin production in erythrocytes). This process is intended to boost fetal hemoglobin (HbF), which can substitute for reduced or absent adult (defective) hemoglobin. ST-400 is then infused back into the patient after receiving conditioning chemotherapy to make room for the new cells in the bone marrow, with the aim of producing new erythrocytes with increased amounts of HbF. The primary objective is to understand safety and tolerability of ST-400, and secondary objectives are to assess the effects on HbF levels and transfusion requirements.

This is a Phase 2, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in adults with non-transfusion dependent beta (β)-thalassemia. The study is divided into the Screening Period, Double-blind Treatment Period (DBTP), Open-label Phase (OLP), and Post-Treatment Follow-up Period (PTFP). It is planned to randomize approximately 150 subjects at a 2:1 ratio of luspatercept versus placebo.

The accumulation of unpaired α-globin chains in β-thalassemia major patients may clinically create ineffective erythropoiesis, hemolysis, and chronic anemia. Multiple blood transfusions and iron overload cause cellular oxidative damage. However, α-tocopherol, an antioxidant, has been known as a potent scavenger of lipid radicals in the red cell membrane of β-thalassemia major patient. By this randomized controlled trial, the investigators would like to evaluate the effects of α-tocopherol in hemolysis and oxidative stress on the red cell membrane of β-thalassemia major.

Primary objectives: To study the tolerance and safety of multiple oral administration of CN128 in patients with thalassemia aged 16 years and above. To study the pharmacokinetics of CN128 in thalassemia patients aged 16 and above by multiple oral administrations of CN128 Design: The study is designed as a safety, tolerability and pharmacokinetic parameters study, phase Ib trial. The study is consisted of: multiple dose tolerance and safety study; multiple administration pharmacokinetics. Subject inclusion criteria: Thalassemia patients with serum ferritin ≥ 500 µg/L Patients aged 16 and above HB≥80 g/L before administration Voluntarily participate in the experiment, and the process of obtaining informed consent met the requirements of GCP. Subject exclusion criteria: Hepatitis B surface antigen positive, hepatitis B core antibody positive and HBV-DNA positive, hepatitis C anti-HCV positive, HIV positive, Treponema pallidum positive History of active digestive tract diseases (including gastric ulcer, duodenal ulcer, gastroesophageal varices, ulcerative colitis, Crohn's disease, digestive tract tumors, familial genetic polyps), history of digestive tract perforation, history of digestive tract surgery and influence on drug absorption, and other investigators believe that patients with potential intestinal complications Liver dysfunction (ALT or AST > 2.5×ULN); or renal dysfunction (serum creatinine > 1.5×ULN) Uncontrolled active infections Patients currently taking CYP3A strong inducer or inhibitor drugs or drugs that may prolong the QT interval without temporary suspension of use or temporary substitution of the said drugs ect. Usage: All subjects fasted prior to administration of study drug using 240 ml warm water. The people can not drink water within 1h before administration. Pharmacokinetic assessment of CN128 administration: PK parameters of CN128 include AUC 0-t, AUC 0-∞, Cmax, Tmax, t1/2, CL/F, Vd/ F, MRT, λz, Css-av, Css-min, Css-max, Accumulation rate, Fluctuation index, etc. Safety and tolerability assessments: Evaluation was based on the incidence rate of adverse events (AE) after the administration, study termination information, vital signs, physical examination, laboratory tests and ECG. Statistics

Beta-thalassemia represents a group of recessive inherited hemoglobin disorders characterized by reduced synthesis of β-globin chain. The homozygous state (β-thalassemia major) "TM" results in severe anemia, which needs regular blood transfusion . The life expectancy in patients with TM has increased due to therapeutically management, such as frequent transfusion, desferal administration and bone marrow transplantation. Diabetes is clinically characterized by hyperglycemia due to either low circulating concentrations of, or decreased sensitivity to, insulin. Patients with TM typically exhibit β-cell or insulin insufficiency, and may develop diabetes due to toxic levels of iron in their pancreas, one of the strongest predictors of β-cell destruction. By contrast, hyperinsulinemia, secondary to insulin resistance, with normal glucose tolerance has also been observed. The pathogenic mechanisms leading from siderosis to diabetes are poorly understood.

The purpose of this observational study is to assess the real-world safety of luspatercept in Korean participants with myelodysplastic syndrome (MDS) or beta thalassemia. Investigators will enroll participants who will begin treatment with at least 1 dose of luspatercept.

Primary objectives: • To evaluate the safety and efficacy of long-term orally administration of CN128 in thalassaemia patients with blood transfusion dependent and aged 16 and above. Design: The study is designed as a single arm and opened phase IIa clinical trial, so as to investigate the safety and efficacy of CN128. A total of 50 eligible subjects are planned to be enrolled, and orally administration of CN128 for 24 weeks or 48 weeks according to the administration plan. The treatment period is from day 0 to 24 weeks, and the extended treatment period was from 25 weeks to 48 weeks. Subjects' medication status, uncomfortable symptoms, concomitant medication or non-drug therapy were recorded daily. Subject inclusion criteria: Thalassemia patients. The number of blood transfusion per month ≥1. Or hemoglobin can not be maintained at 90g/L above, if blood transfusions is less than once per month. Serum ferritin ≥ 500 µg/L Patients aged 16 and above Volunteer for the trial and sign the informed consent. Subject exclusion criteria: Active hepatitis B (HBsAg positive, HBsAb negative) or hepatitis C (HCV antibody positive, detectable HCV RNA, and alanine transaminase (ALT) beyond normal range) Active gastrointestinal disease history (including: gastric ulcer, duodenal ulcer, stomach or esophageal varices, ulcerative colitis, Crohn's disease, gastrointestinal cancer, familial genetic multiple intestinal polyps), and History of gastrointestinal perforation, gastrointestinal surgery that influence drug absorption, and other potential intestinal complications considered by researchers; ALT or Aspartate transaminase (AST) > 2.5 × Upper limit of normal (ULN), or serum creatinine > 1.5 × ULN; Neutropenia patient (neutrophil count < 1.5 × 109 / L); Active infection uncontrolled; The patients who are currently taking CYP3A strong inducer or strong inhibitor drugs, or the drug that may extend the QT interval, or the drug that may decrease neutrophil count, but can not temporarily interrupt the use of such drugs; Congenital long QT syndrome or known family history of long QT syndrome; QTc > 480 ms; clinically significant ventricular or atrial fast arrhythmia; etc. Usage: All subjects will be given the lower (10 mg/kg bw, bid) or higher dose (15 mg/kg bw, bid) for 24 or 48 weeks, according to the administration plan. Safety assessments: Safety evaluations include adverse events, adverse reactions, severe adverse events, and severe adverse reactions; growth; total and free testosterone in men, follicle-generating hormone and luteinizing hormonin in women; vital signs and electrocardiogram; hearing, laboratory test, urine pregnancy test (women of childbearing age), etc. Efficacy assessments: Efficacy evaluations include serum ferritin, liver iron content (MRI R2) and cardiac iron content (MRI T2*). Statistics: Subject characteristic distribution Demographic characteristics, general conditions, and baseline conditions (pre-treatment) of enrolled subjects were analyzed.The measurement data are described by means, standard deviation, minimum value and maximum value, while the qualitative data list frequency and percentage. Safety analysis Descriptive statistical analysis was used for safety endpoints. Effectiveness analysis Mean, standard deviation, median, minimum and maximum values were described and 95% confidence intervals were calculated. Paired T-test was used to compare each time point with the baseline if necessary. The 95% confidence interval was calculated by using Clopper-Pearson method for the proportion of patients.

Patients with severe thalassemia (thalassemia major) present with severe anemia that required life-long transfusion therapy, spleen enlargement that led to increased transfusion requirement, and other serious complications as early death, growth retardation, bone deformations and iron overload due to blood transfusions. Splenectomy can significantly reduce transfusion requirement in thalassemia patients, but it is associated with an increased risk of serious complications such as sepsis and thrombosis. Preliminary preclinical and clinical data suggested that JAK2 inhibition, by reducing spleen size, could improve hemoglobin levels, thereby eliminating the need for splenectomy and reducing transfusion requirement and related iron overload.

effect of B blocker was first evaluated in patient with cardiomyopathy not induced by ischemia and idiopathic which as the most common causes of cardiomyopathy. Effect of BB on Thalassemia cardiomyopathy was evaluated in this study