Sickle Cell Disease

Researchers are studying the smallest effective dose of 131I-apamistamab to prepare patients with advanced sickle cell disease (SCD) for a bone marrow transplant. This is the first time 131I-apamistamab, an investigational drug not yet approved by the FDA, is being used as part of the conditioning regimen before an allogeneic stem cell transplant. The goal is to see if eliminating total body irradiation, which can cause long-term side effects, is possible while still allowing successful transplantation. Participants will receive 131I-apamistamab as an intravenous infusion about ten days before receiving donor stem cells. The dose will be either 100 mCi or 150 mCi based on the dose level. This drug replaces the usual conditioning treatments like chemotherapy, total body irradiation, and Campath antibody. Other treatments involved include sirolimus and Campath, given to support the transplant process. During the study, participants will undergo various assessments including blood tests to monitor graft success, immune recovery, hormone levels, and transplant-related complications up to seven years after transplant. Imaging with planar gamma camera will evaluate drug absorption. Follow-up includes checking for graft failure 42 days post-transplant and monitoring long-term safety. Total participation lasts several years to observe transplant outcomes and side effects.

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 DISC-3405, a drug being studied in adults with sickle cell disease (SCD). This open-label, multicenter study focuses on examining up to three dose levels of DISC-3405 to assess its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in participants with SCD. The study is led by Disc Medicine, Inc and aims to better understand how this drug behaves and affects blood markers in people with this condition. Participants will receive DISC-3405 administered by subcutaneous injection in a within-participant dose escalation design. The study will explore up to three different doses of the drug to observe how participants respond to each level. This approach allows researchers to evaluate safety and drug effects at increasing dose amounts. The study lasts up to 36 weeks and includes multiple assessments during this time. Throughout the study, participants will undergo regular monitoring of safety and tolerability as the primary outcome. Researchers will also measure changes in blood-related markers like hemoglobin, hematocrit, reticulocyte count, red blood cell count, lactate dehydrogenase, and bilirubin. Pharmacokinetic measures such as drug concentration over time, maximum plasma concentration, elimination half-life, and clearance will also be tracked. Participants must be able to comply with study procedures, including providing informed consent and attending all visits during the trial period.

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 2/3 study focuses on both adults and adolescents with SCD, aiming to determine the best dose and assess the drug's 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 osivelotor's 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 drug's 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 studying ITU512, an oral investigational drug, to evaluate its safety, tolerability, how it is processed in the body, and its ability to increase fetal hemoglobin (HbF) levels. This study includes both healthy adults and adolescents or adults with sickle cell disease (SCD). It is a global, randomized Phase I/II trial and represents the first time ITU512 is tested for potential therapeutic effects in these groups. The study is divided into two main parts: Part 1 involves healthy participants and consists of three subparts (1A, 1B, and 1C), focusing on safety, tolerability, pharmacokinetics, and preliminary food effects of ITU512. Part 2 is conducted in patients with sickle cell disease and includes Parts 2A and 2B, assessing safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of ITU512, with an optional extension (Part 2C) for further evaluation. Participants will undergo various assessments such as monitoring adverse events, dose adjustments, and measuring fetal hemoglobin percentages up to several months. Blood and urine samples will be collected to study drug concentration and effects on hemoglobin. Safety will be closely monitored through ECGs, vital signs, laboratory tests, and physical exams. The total participation time varies by study part, with some assessments lasting up to five months.

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.

Researchers are studying etavopivat, a new oral medicine being developed to treat inherited blood disorders such as sickle cell disease and thalassaemia. These conditions affect haemoglobin, the protein that carries oxygen in the blood. This phase 3 open-label study aims to assess the long-term safety and effectiveness of etavopivat in adults, adolescents, and children who have completed treatment in an earlier etavopivat study. The study is sponsored by Novo Nordisk A/S and may last up to 264 weeks unless etavopivat is approved earlier in the participant's country. Participants will receive an oral dose of etavopivat, with dosing varying by age and condition. Those aged 12 years or older will receive either Etavopivat A or C, while children under 12 years old will receive Etavopivat B. The study includes groups with sickle cell disease or thalassaemia, some of whom may be transfusion-dependent. The treatment will be continuous throughout the study period, aiming to observe long-term effects and safety. During the study, participants will be closely monitored for treatment-emergent adverse events and adverse reactions. Researchers will track clinical outcomes such as vaso-occlusive crisis rates, hemoglobin levels, hospitalizations, and red blood cell transfusions, both at baseline and throughout treatment. Data will be collected regularly to assess safety and treatment impact across different age groups and disease types, with the total study duration potentially extending to over six years.