Common Variable Immunodeficiency (CVID)

This research aims to evaluate the safety of Immune Globulin Subcutaneous (Human), 20% Solution in people with primary immunodeficiency diseases (PID) using data from a medical database in Japan called PIDJ2. The study is observational and involves reviewing existing patient records to learn about the treatment's safety in this group. It is sponsored by Takeda and focuses on important safety concerns related to this treatment. Participants included in the study are those with PID who have received the Immune Globulin Subcutaneous (Human), 20% Solution according to the treatment guidelines. The study collects data retrospectively from the PIDJ2 registry, which tracks patients over time. The treatment was given as an infusion following the approved package instructions. Participants' medical records will be reviewed to identify any adverse events such as anaphylactic reactions, thromboembolism, or aseptic meningitis occurring from the start of treatment up to five years. This long-term safety monitoring uses the registry data without new treatment or visits. The study period extends through July 2030, focusing on real-world safety outcomes for people with PID receiving this therapy.

Researchers are studying the use of unlicensed cryopreserved cord blood units (CBUs) for transplantation in both pediatric and adult patients with various blood-related cancers and other disorders affecting the blood-forming system. This observational study aims to evaluate outcomes such as the recovery of a certain level of white blood cells after transplantation, as well as the incidence of infections, infusion reactions, survival rates, and graft-versus-host disease over time. The study involves patients receiving unlicensed CBUs at multiple U.S. transplant centers. These CBUs are used for patients with hematologic malignancies and other blood disorders. The protocol collects data on patients who receive these unlicensed transplant units, without administering a new treatment but observing the outcomes after transplantation. Participants will be monitored for neutrophil recovery at 60 and 100 days post-transplant, along with assessments of infection transmission, infusion reactions, survival one year after transplant, and occurrences of acute and chronic graft-versus-host disease. Platelet engraftment levels will also be tracked. The study includes patients of any age and follows them through the transplantation and recovery process to gather information on these key outcomes.

Researchers are investigating the use of allogeneic hematopoietic stem cell transplantation (HSCT) to treat VEXAS Syndrome, a newly identified disease characterized by inflammatory and blood-related problems. This syndrome involves symptoms such as fever, skin lesions, and bone marrow failure, often resistant to standard treatments. The study aims to determine if HSCT can successfully replace the patient's bone marrow with donor cells and improve or reverse the disease's clinical features over time. Participants will receive a stem cell transplant from a matched or haploidentical donor after undergoing a reduced intensity conditioning regimen tailored to the donor match type. This includes drugs like fludarabine, busulfan, cyclophosphamide, and possibly low-dose total body irradiation. After the transplant, participants will receive medications such as mycophenolate mofetil and tacrolimus to prevent graft-versus-host disease. The transplant is given via a central venous catheter, and participants must stay near the hospital for at least 100 days with frequent follow-up visits. During the study, participants will undergo extensive screening including physical exams, imaging scans, blood and urine tests, bone marrow biopsies, and specialist consultations. Post-transplant, they will attend scheduled visits up to two years after receiving the transplant to monitor donor cell engraftment, disease reversal, safety outcomes, and any complications like graft-versus-host disease. The study includes yearly follow-ups by phone after two years, with total participation possibly extending beyond three years.

Researchers are evaluating the safety and activity of sparsentan for treating adult patients with biopsy-confirmed immunoglobulin A nephropathy (IgAN), including newly diagnosed patients who have not received prior ACEI or ARB therapy (Cohort A) and patients with recurrent IgAN after kidney transplantation (Cohort B). This open-label, multi-center trial aims to explore sparsentan's potential to protect kidney function over an extended period. In Cohort A, patients will start sparsentan at 200 mg daily, increasing to a target dose of 400 mg daily after two weeks if tolerated, with dose adjustments allowed to maintain the highest tolerable dose. Treatment will continue for 110 weeks, followed by a 4-week off-treatment follow-up. Cohort B patients will be randomly assigned to receive sparsentan plus standard care for 48 weeks or standard care alone for 24 weeks before adding sparsentan for the remaining 24 weeks, then followed by a 4-week follow-up. Additional antihypertensive treatments are allowed except for ACEIs, ARBs, aldosterone blockers, or aliskiren. Participants will undergo assessments including urine protein excretion, estimated and measured glomerular filtration rate (GFR), kidney biopsy analysis using the Oxford Classification, MRI for kidney and heart function, bioimpedance for body water, and quality of life evaluations. Safety will be monitored through adverse events, lab tests, and vital signs. The primary outcome is urine protein/creatinine ratio at Week 36, with secondary outcomes assessing kidney function, proteinuria changes, and safety over up to 114 weeks.

Researchers are evaluating whether emapalumab or a combination of fludarabine and dexamethasone can effectively prepare people with primary immune regulatory disorders (PIRD) and/or autoinflammatory conditions for stem cell transplants. The study aims to see if these treatments reduce inflammation and help donor stem cells successfully engraft, enabling the immune system to produce fully functioning cells. This is a phase 2 study supported by the FDA Office of Orphan Products Development. Participants are assigned to one of two groups based on their inflammation type. Group A participants with a high CXCL9 cytokine level receive emapalumab on days -22, -15, -8, and -1 before the transplant. Group B participants with generalized inflammation receive fludarabine and dexamethasone for five consecutive days from days -22 to -18. All participants undergo a standard stem cell transplant on day 0 and may receive an additional emapalumab dose within 30 days post-transplant if inflammation markers rise. During the study, participants remain hospitalized according to usual care and have follow-up visits on days 0, 7, 14, 21, 30, 45, 60, 70, 100, 180, 270, and 365, then quarterly for up to three years. Researchers monitor engraftment success, survival rates, graft-versus-host disease incidence, immune recovery, quality of life, and other health outcomes. Data collection continues long-term to assess transplant effects and safety.

Researchers are evaluating whether biweekly doses of XEMBIFY4 combined with Standard Medical Treatment (SMT) over one year can reduce major bacterial infections in adults with hypogammaglobulinemia (HGG) linked to B-cell Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM), or Non-Hodgkin Lymphoma (NHL). The study compares this combination to placebo plus SMT in participants who have recurrent or severe infections and lower IgG levels. Participants are randomly assigned to receive either XEMBIFY or a placebo through subcutaneous infusion pumps. Both groups get a loading dose given daily for five days starting in Week 1, followed by biweekly infusions from Week 3 through Week 51. Throughout the study, all participants continue receiving their usual supportive medical treatments as part of SMT. During the year-long treatment phase, participants will be monitored for the rate of major bacterial infections as the main outcome. Additional assessments include the timing and frequency of infections, antibiotic use, and hospitalization details related to infections. Safety and pharmacokinetics are also evaluated, with follow-up visits scheduled regularly until the study ends in June 2026.

Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of an anti-GPRC5D CAR-T cell product called OriCAR-017 in adults with relapsed or refractory multiple myeloma. This Phase I/II open-label study is the first clinical trial of OriCAR-017 in the United States by OriCell Therapeutics Co., Ltd., aiming to find suitable dosing and assess early treatment results in this patient group. The study includes a Phase I dose escalation stage with three different doses given as a single intravenous infusion to up to 18 participants. This is followed by a dose expansion stage with 10-15 participants and then a Phase II stage that may include up to 48 participants. Each participant receives one infusion of OriCAR-017 to evaluate its effects and safety. Participants will be closely monitored for up to two years after treatment. Researchers will assess the maximum tolerated dose and dose-limiting toxicities within 28 days after infusion. They will also study how the drug moves through and affects the body, measure response duration, progression-free survival, overall survival, and other response rates. Regular evaluations include laboratory tests, clinical assessments, and safety monitoring throughout the study period.

Researchers are evaluating OPF-310, which consists of encapsulated porcine islet cells for xenotransplantation, in adults with unstable Type 1 Diabetes Mellitus (T1DM). This first-in-human study aims to assess the safety, tolerability, and effectiveness of OPF-310 transplantation and to determine the recommended Phase 2 dose (RP2D). Eligible participants have experienced severe hypoglycemic episodes despite treatment with a closed loop system (CLS) for at least six months. Participants will receive OPF-310 in an open-label trial with ascending doses. Initially, three subjects will receive 6,000 islet equivalents (IEQ)/kg and three will receive 12,000 IEQ/kg, both followed by safety monitoring. Then, seven more subjects will receive the recommended Phase 2 dose determined from earlier results. A total of 13 patients will be transplanted with OPF-310. During the study, researchers will monitor participants for up to one year after transplant. They will assess outcomes such as reduction in severe hypoglycemic events, improvements in glucose control measured by continuous glucose monitoring (CGM), insulin use, and HbA1c levels. Other evaluations include porcine C-peptide levels, psychological impact assessments, and hypoglycemia awareness. Safety and tolerability will also be closely observed throughout the study period.

Researchers are evaluating abatacept as a treatment for granulomatous-lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID), a condition without a standard therapy. This multi-site, phase II randomized, blinded, placebo-controlled clinical trial includes both pediatric and adult participants to compare the effects of abatacept against placebo. The study aims to assess the efficacy of abatacept in this complex immune condition, funded by the FDA Office of Orphan Products Development. Participants are divided into two cohorts based on weight. Cohort 1 includes pediatric subjects weighing 50 kg or more and adults, randomized in a 1:2 ratio to receive either abatacept or placebo weekly for six months, followed by open-label abatacept for all. Cohort 2 includes pediatric subjects under 50 kg receiving open-label abatacept with dosing based on weight. After the initial 12 months, patients can opt to continue abatacept treatment for up to three years, with safety monitoring every three months. During the study, participants will undergo assessments including high-resolution chest CT scans, lung function tests such as forced vital capacity and forced expiratory volume, quality of life questionnaires, and monitoring for infections and adverse events at 6 and 12 months. Additional evaluations include pediatric growth measures and steroid use. Safety monitoring continues for those opting for extended treatment, ensuring a comprehensive overview of abatacept’s effects over time.

Researchers are evaluating real-world treatment patterns and clinical outcomes in patients aged 12 years and older with moderate-to-severe atopic dermatitis who are receiving abrocitinib. The study aims to describe patient demographics and baseline characteristics over a 12-month observation period to better understand how abrocitinib is used in usual clinical practice conditions. Participants will be newly prescribed abrocitinib as decided by their physician during routine care. The study does not involve experimental treatments but observes how abrocitinib is used and its effects in everyday settings. There are no comparator groups or placebo treatments since this is an observational study. During the 12-month observation, researchers will track improvements in eczema severity using measures like the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and patient-reported outcomes such as the Peak Pruritus Numerical Rating Scale (PP-NRS). Data on treatment duration, quality of life, and symptom changes will also be collected. Patients' progress will be monitored at multiple time points including weeks 2, 4, 12, 16, 24, and 52.