Hemoglobinopathy

This NIH-sponsored study aims to characterize three biomarkers derived from 129Xe gas exchange MRI and understand how they change in response to interventions. The study focuses on markers derived from the interaction of 129Xe with pulmonary capillary red blood cells RBCs, specifically RBC transfer MRI, cardiogenic oscillations in 129Xe-RBC signal amplitude, and the 129Xe-RBC chemical shift. The study population includes healthy volunteers, patients scheduled to undergo transfusion or phlebotomy, patients with dyspnea, interstitial lung disease ILD, idiopathic pulmonary fibrosis IPF, non-specific interstitial pneumonias NSIP, chronic hypersensitivity pneumonitis cHP, sarcoid, chronic thromboembolic pulmonary hypertension CTEPH, and acute pulmonary embolism.

Researchers are investigating the minimum effective dose of 131I-apamistamab as part of a conditioning regimen for patients with advanced sickle cell disease SCD undergoing hematopoietic stem cell transplantation. This Phase 1, single-center study focuses on patients aged 12 to 50 years with sickle cell anemia and an available HLA-matched sibling donor. The study aims to replace the typical conditioning regimen, which includes chemotherapy, total body irradiation, and Campath antibody, with 131I-apamistamab to potentially reduce long-term side effects such as secondary cancers, infertility, cataracts, and lung toxicity. Participants will receive 131I-apamistamab as an intravenous infusion approximately ten days before receiving donor stem cell infusion. The dose of 131I-apamistamab will be personalized and prepared in advance, with target dose levels of either 100 mCi or 150 mCi. Additional treatments may include oral sirolimus to suppress immune response and intravenous Campath antibody. Other procedures such as total body irradiation and red blood cell exchange transfusions may also be part of the overall treatment process, following institutional practices. During the study, participants will undergo various assessments including blood tests, hormone level measurements, and imaging scans to monitor drug absorption and treatment effects. Researchers will evaluate outcomes such as graft failure rate 42 days after transplant, event-free survival, engraftment times for neutrophils and platelets, incidence of graft-versus-host disease, transplant-related toxicities and infections, donor cell presence, and immune recovery. Hormonal evaluations related to fertility will be measured at study start and one year post-transplant. The study includes long-term follow-up of up to seven years to assess these outcomes and safety.

The GENESIS clinical study aims to map HLA genetic variation in the Greek population and evaluate possible correlations with selected underlying diseases. It is a multicenter, prospective, non-interventional clinical study targeting 12,000 subjects over an anticipated duration of 36 months, with the goal of creating a pilot HLA map for medical research and possible clinical applications. Each subject will complete one visit at a participating site and provide demographic information, including date of birth, gender, race, ancestry, height, and weight, as well as information about smoking or vaping, alcohol consumption, arterial blood pressure, diagnosed diseases, and current treatments. Recent clinical laboratory results from up to 12 months before sample collection may also be collected when available, including blood count, metabolic, liver enzyme, and biochemical parameters. Two buccal swabs will be collected from each subject for DNA extraction and HLA genotyping analysis. Selected DNA samples will also undergo low-pass whole genome sequencing to further investigate associations between the HLA region and autoimmune diseases. After the analysis is completed, an individualized ancestry report will be securely available to study subjects if they elect to access it.

This research aims to evaluate the long-term safety and effectiveness of CS-101 in participants who previously received CS-101 in an earlier study CS-101-03. It focuses on individuals with beta-thalassemia who underwent treatment with this base-edited autologous hematopoietic stem cell transplantation. The study is led by the Childrens Hospital of Fudan University and monitors participants up to two years after their infusion. Participants in this follow-up study have completed the initial CS-101-03 trial where they received the CS-101 infusion. This current study tracks their health and treatment outcomes for up to two years after the last six-month follow-up visit post-infusion. The study does not introduce new treatments but observes the long-term effects of the prior CS-101 therapy. During the study, participants will undergo evaluations for serious adverse events, death, new cancers or blood disorders, and whether they achieve transfusion independence for at least 12 consecutive months. Researchers will also monitor changes in fetal and total hemoglobin levels, and the genetic modification presence in blood and bone marrow cells. All assessments occur from the time of consent through two years post-infusion, with safety and efficacy carefully observed throughout this period.

This research follows patients with Hemoglobinopathy and Sickle Cell Disease who previously received BEAM-101, a gene-edited cell treatment, in an earlier study. The trial is a long-term observational follow-up to monitor safety and health outcomes over an extended period. It aims to gather important information about the long-term effects and risks after receiving BEAM-101 treatment. Participants in this study have received a single dose of BEAM-101 by intravenous infusion after a conditioning treatment with busulfan. This follow-up study will track their health for 13 years, adding up to 15 years from the initial treatment. Study visits will happen annually for the first 5 years, then every 3 years until year 11, with a final visit at year 15. Additionally, virtual or phone check-ins will occur every 6 months for the first 5 years, then annually thereafter. During the study, participants will undergo regular safety and efficacy assessments to monitor their health, including how well they remain free of severe sickle cell crises and their blood hemoglobin levels. Researchers will review long-term safety data and mortality over the 13 years. The study includes blood tests and other evaluations at scheduled visits and check-ins. Participation will last up to 15 years, with ongoing monitoring to understand the lasting impact of BEAM-101 treatment.

Researchers are evaluating 9MW3011, a drug being studied in patients with non-transfusion-dependent beta-thalassemia, a condition affecting blood production. This phase Ib, randomized, double-blind, placebo-controlled study aims to assess the safety, tolerability, how the drug moves and acts in the body, and immune responses to 9MW3011. The study involves 40 patients divided into four dose groups to explore these effects carefully. Participants will receive either 9MW3011 or a placebo through intravenous infusion in a 41 ratio within each dose group. The study has multiple ascending dose cohorts to test increasing doses of 9MW3011. This design helps researchers understand the drugs impact at different dose levels and compare it to a placebo under blinded conditions. During the study, participants will be monitored up to day 169 for adverse events, vital signs, physical exams, ECG results, and lab tests to evaluate safety. Researchers will measure drug levels in the blood, effects on iron metabolism markers, immune responses, and liver iron concentration. Participants will be involved in scheduled visits for assessments, tests, and safety monitoring throughout the study duration.

Researchers are evaluating a new combination of evidence-based interventions EBIs aimed at improving diagnostic safety and efficiency in primary care for patients with anemia and decreased glomerular filtration rate. The study is designed as a stepped wedge cluster randomized control trial to measure how these interventions affect patient safety and healthcare efficiency, while also assessing factors influencing their implementation such as acceptability, cost, and sustainability. The study compares an enhanced diagnostic team approach to usual care. The enhanced approach includes automated detection and tracking of abnormal test results, expanding the primary care team to include clinical pharmacists to guide anemia evaluation, and engaging patients through nurse navigators to increase their activation in the diagnostic process. The study involves several clinic groups that receive the intervention at different times, ranging from 12 to 24 months, with some initial control periods. Participants will have their diagnostic accuracy for causes of low hemoglobin and decreased glomerular filtration rate assessed within six months. Researchers will track time to diagnosis, appropriate test usage, treatment costs, and primary care physicians views on the interventions acceptability and feasibility. The study also monitors how well the diagnostic process steps are followed, the interventions reach among patients, and sustainability in clinics over 2.5 years. Patient activation and clinic-level facilitators and barriers are evaluated through surveys and measures during the study period.

Researchers are evaluating the safety, tolerability, and effectiveness of a gene therapy treatment called BD211 for patients aged 3 to 35 years with transfusion-dependent beta-thalassemia. This condition requires regular blood transfusions, and the study aims to assess how well the gene-modified stem cells work and how safely they can be used. The study is a Phase 1, open-label trial sponsored by Shanghai BDgene Co., Ltd., focusing on patients who need frequent transfusions and have limited treatment options. The treatment involves a single intravenous infusion of BD211, which consists of autologous CD34 hematopoietic stem cells that have been genetically modified with a lentiviral vector to produce healthy beta-globin. Participants receive one dose of at least 5 million cells per kilogram of body weight. The study includes an 18-month follow-up period to monitor safety endpoints and effectiveness, including the ability to reduce or eliminate the need for transfusions. During the study, participants undergo regular assessments to track neutrophil and platelet engraftment, transfusion independence, blood hemoglobin levels, ferritin levels, and the presence of the beta-globin protein in blood. Researchers also monitor for adverse events, survival rates, hospitalizations, and any signs of complications related to the gene therapy. Participants are expected to comply with scheduled visits, laboratory tests, and long-term follow-up assessments to help determine the treatments overall safety and efficacy.

Researchers are conducting an open-label, multicenter study to evaluate DISC-3405 in adults with sickle cell disease SCD. The study examines up to three different dose levels of DISC-3405 to assess its safety, tolerability, pharmacokinetics PK, and pharmacodynamics PD. This Phase 1b trial focuses on participants with SCD, including those with certain complications related to the disease. In this study, DISC-3405 is given by subcutaneous injection in a within-participant dose-escalation design, meaning each participant may receive increasing doses over time. The study examines up to three dose levels sequentially to evaluate how the body processes the drug and how the drug affects blood markers related to SCD. The treatment period can last up to 36 weeks, during which safety and PD measures are closely monitored. Participants will be involved throughout the treatment period with regular assessments including blood tests to measure hemoglobin, hematocrit, reticulocyte count, red blood cell count, lactate dehydrogenase, bilirubin levels, and drug concentrations in blood. Safety and tolerability are primary concerns, with follow-up evaluations up to 36 weeks. Participants must comply with study procedures and provide informed consent before enrollment, ensuring they understand the studys aims and requirements.

Researchers are studying etavopivat, a new medicine, in children aged 12 to 16 years with sickle cell disease who have an increased risk of stroke. The trial focuses on patients with conditional or abnormal transcranial doppler TCD ultrasound results, assessing whether etavopivat is safe and helpful for these participants. The study is a Phase 2 open-label trial sponsored by Forma Therapeutics, Inc., aiming to understand the effect of etavopivat on blood flow velocities in brain arteries. Participants will be divided into two groups based on their TCD results and whether they are already taking the medication hydroxyurea. One group includes participants with abnormal or conditional TCD who are not on hydroxyurea, while the other group includes those with similar TCD results who are on a stable dose of hydroxyurea. All participants will take 400 mg of etavopivat orally once daily for 52 weeks, with the option to continue in a 48-week extension period to further monitor safety. Etavopivat is taken as two 200 mg tablets and may be taken with or without food. During the study, participants will visit the clinic frequently for monitoring. Assessments include measuring blood flow velocities in brain arteries using TCD at various time points, tracking changes in velocity categories, and monitoring safety. The study also includes evaluating blood counts and liver and kidney function. At the end of the treatment and extension periods, participants may be offered the chance to join another study to continue receiving etavopivat. Total participation can last up to about two years depending on extension and further studies.