Sickle Cell Disease

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.

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.

Diffuse large B-cell lymphoma DLBCL is the most common and aggressive subtype of non-Hodgkin lymphoma, with rapid tumor growth and symptoms varying by tumor location. The disease is classified using advanced methods like immunohistochemistry and molecular testing to guide prognosis and personalized treatment. Despite standard immunochemotherapy curing 60-70% of patients, many experience treatment failure or relapse, and options after second-line therapies remain limited. This observational study examines treatment patterns, demographic, and clinical characteristics of DLBCL patients in the Middle East and Africa. It includes two patient groups those newly diagnosed and eligible for treatment, and those with relapsed or refractory DLBCL who have failed previous therapies. The study aims to explore access to novel therapies and understand real-world treatment approaches in these regions. Participants will be observed over 22 months, during which researchers will document treatment regimens, patient risk profiles, and access to new treatments. Data collection includes patient demographics, disease characteristics, and treatment outcomes. The study does not involve experimental treatments but gathers detailed information to inform future care strategies for DLBCL patients.

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.

Researchers are evaluating the safety, tolerability, effectiveness, and how the body processes and responds to osivelotor in people with sickle cell disease SCD. This multicenter, Phase 23 study focuses on both adults and adolescents with SCD, aiming to determine the best dose and assess the drugs effects over time. The study has three parts. Part A tests safety, tolerability, and dose-finding in adults with SCD, starting with randomization to different daily doses of osivelotor, ranging from 100 mg to potentially 200 mg, over 12 weeks. Part B compares osivelotor to placebo in adults and adolescents over 48 weeks, with adults receiving an initial 300 mg daily dose for 7 days followed by 150 mg daily, while adolescent dosing will be defined later. The Open Label Extension OLE offers long-term open-label osivelotor treatment for up to two years after Part B. Participants will be monitored throughout the study with regular visits to assess safety, blood responses, and how well they tolerate the medication. The main results will be reviewed through 12 weeks in Part A, 48 weeks in Part B, and approximately 24 months in the OLE. The study includes blood tests, monitoring of vaso-occlusive crises, and other health evaluations to understand osivelotors effects and safety over time.

Researchers are studying SNH-119014, an oral small-molecule drug that targets the pyruvate kinase red blood cell isozyme PKR, to understand its safety, tolerability, and how the body absorbs and responds to it. This phase 1 trial involves healthy adult volunteers to gather initial information about the drugs effects and how food influences its absorption. The study involves giving participants either single ascending doses or multiple ascending doses of SNH-119014 or a placebo in a randomized, controlled manner. The treatment is administered orally, and the study uses a quadruple-masked design to compare effects without bias. Participants will undergo regular monitoring including physical examinations, vital signs checks, ECGs, and laboratory tests to detect any abnormal findings or adverse events related to the study drug. The primary outcome focuses on safety measures up to 7 or 20 days after dosing. The total participation duration and follow-up are designed to ensure thorough assessment of drug effects and safety in healthy adults aged 18 to 45 years.

Researchers are evaluating ITU512, an investigational oral drug, in healthy adults and patients with sickle cell disease SCD to study its safety, tolerability, how it is processed by the body pharmacokinetics, and its potential to increase fetal hemoglobin levels. This Phase III study is the first to assess ITU512s possible therapeutic effects in these groups, aiming to better understand its impact on SCD. The study is divided into two parts Part 1, a first-in-human Phase I trial involving healthy participants, and Part 2, a Phase II trial including patients with SCD. Part 1 includes three subparts 1A, 1B, 1C to examine safety, dosage, and food effects in healthy adults. Part 2 has two subparts 2A, 2B plus an optional extension 2C focusing on safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy in adolescents and adults with SCD. Participants may receive ITU512 or placebo in a randomized, double-blind crossover design. During the study, participants undergo various assessments including medical exams, vital signs, ECGs, and blood and urine tests to monitor drug levels and effects on fetal hemoglobin and other blood parameters. Safety is closely tracked with attention to adverse events and dose adjustments. The study includes up to 5 months of active treatment and follow-up, with detailed monitoring of outcomes such as adverse events, dose interruptions, and fetal hemoglobin percentage. Participant involvement includes scheduled visits for dosing and evaluations throughout the study timeline.

Sickle Cell Disease SCD affects oxygen transport and causes damage to blood vessels, especially impacting the brain. Researchers are evaluating new ways to monitor SCD and its treatments by measuring brain blood flow, oxygen use, and blood vessel function using advanced MRI and optical techniques. This study aims to find biomarkers to guide when treatment is needed and measure how well treatments work for each patient, helping to personalize care and support future SCD therapies. Participants are grouped based on their SCD status and treatments healthy children without SCD, children with SCD not receiving treatment, children who have had gene therapy, and children on chronic transfusions. All participants undergo an MRI scan lasting about an hour combined with simultaneous optical monitoring. Those on chronic transfusions have additional MRI scans and optical tests before, during, and after transfusions to track changes. During the study, participants will have one or two MRI sessions with simultaneous optical measurements to assess brain oxygen transport and blood vessel response. Researchers will collect data on how these measurements change with treatment and compare groups with different SCD statuses. The main outcome is the accuracy of the optical device FDNIRS-DCS in measuring brain blood oxygen levels over six months. The study runs until August 2027 and involves children aged 8 to 18 years.

Researchers are gathering detailed real-world information on people with chronic wounds and ulcers to better understand their medical journey and treatment outcomes. This observational registry collects data from over 1,400 healthcare providers across the USA and Puerto Rico using a specialized electronic health record system. It includes all major wound types such as diabetic foot ulcers, venous leg ulcers, pressure ulcers, arterial ulcers, surgical wounds, traumatic wounds, and inflammatory ulcers. Participants receive care as usual from their clinicians, who use standard and advanced wound treatments like specialized dressings, compression therapy, offloading devices, cellular and tissue-based products, negative pressure therapy, ultrasound therapy, topical oxygen, hyperbaric oxygen, growth factors, debridement, and topical antibiotics. Data on treatment practices, wound characteristics, patient health conditions, and complications are collected continuously during routine care. Patients may be followed for over five years to track long-term outcomes. During the study, researchers collect information on patient demographics, wound details, treatment methods, visit frequency, and complications. They monitor healing progress, amputations, deaths, wound recurrence, hospitalizations, and other outcomes. The registry uses a wound healing index to adjust for risk and supports quality improvement and research by linking clinical data with insurance claims for comprehensive analysis. This ongoing effort helps to better understand wound healing and treatment effectiveness in everyday healthcare settings.