Common Variable Immunodeficiency (CVID)

Researchers are evaluating the safety of Immune Globulin Subcutaneous Human, 20% Solution in people with primary immunodeficiency disease PID using a retrospective medical database in Japan called PIDJ2. This observational study collects information about patients who have received this treatment as part of routine care to better understand potential adverse events. The study is sponsored by Takeda and uses existing patient registry data to assess safety outcomes. Participants included in this study are those with PID who have received Immune Globulin Subcutaneous Human 20% infusion following the official package instructions. The study does not administer treatments but analyzes data from the PIDJ2 database collected between January 24, 2024, and January 23, 2029. It focuses on patients whose records include details about use of the study drug and documented adverse events. During the study, researchers will review the database to identify any participants who experienced specific adverse events such as anaphylactic reactions, thromboembolism, or aseptic meningitis up to five years from the initial registration or first dose. The study involves no direct visits or interventions, as it is based on reviewing existing records. The total study period extends until March 31, 2030, allowing long-term safety observations.

Researchers are studying the use of unlicensed cryopreserved cord blood units CBUs for transplantation in both children and adults with blood cancers and other related disorders. This observational study involves patients with hematologic malignancies and various inherited and acquired disorders affecting the blood and immune system. The main goal is to monitor how well neutrophil recovery occurs after transplantation using these unlicensed CBUs in multiple institutions. Participants receive unlicensed cryopreserved CBUs as part of their transplant treatment. The study includes patients of any age receiving these CBUs for approved indications. The protocol focuses on the access and distribution of these unlicensed units rather than a specific treatment intervention. The study gathers data from recipients who receive these CBUs, tracking outcomes after transplantation. Participants are monitored for neutrophil recovery at 60 and 100 days after transplant, defined by a neutrophil count of at least 500mm3. Researchers also collect information on infection transmission, infusion reactions, survival rates at one year, and incidence of acute and chronic graft versus host disease. Platelet recovery is also evaluated. Safety and efficacy outcomes are followed over time to better understand the effects of unlicensed CBUs in this patient population.

Researchers are studying whether allogeneic hematopoietic stem cell transplantation HSCT can be successfully performed in adults aged 18 to 75 with VEXAS Syndrome, a condition involving severe inflammatory and blood-related problems that are often resistant to standard treatments. This disease causes systemic inflammation and bone marrow failure, leading to serious health issues and increased mortality. The study aims to see if HSCT can reverse the disease symptoms and achieve sustained donor cell engraftment. Participants receive different reduced intensity conditioning regimens depending on their donor match status before undergoing HSCT. Those with an 88 HLA matched donor receive fludarabine and busulfan, while those with a 78 matched or haploidentical donor receive fludarabine, cyclophosphamide, total body irradiation, and busulfan. After transplant, all participants receive drugs to prevent graft-versus-host disease GVHD, including cyclophosphamide, mycophenolate mofetil, and tacrolimus. These treatments are given according to a detailed schedule around the transplant day. Participants undergo extensive screening including physical exams, blood and urine tests, imaging scans, and specialist evaluations. After transplant, they stay in or near the hospital for at least 100 days with weekly visits, followed by study visits at 30, 60, 100, 180, 210, 240, 300, and 360 days post-transplant, then yearly visits for two years and annual phone contacts thereafter. Researchers monitor disease reversal, donor cell engraftment, safety, GVHD incidence, survival, and other outcomes over several 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 sparsentans 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 proteincreatinine 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 andor 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.

This research aims to evaluate whether administering XEMBIFY every two weeks alongside Standard Medical Treatment SMT over a one-year period can reduce the number of major bacterial infections each year in adults with low antibody levels hypogammaglobulinemia who have B-cell Chronic Lymphocytic Leukemia CLL, Multiple Myeloma MM, or Non-Hodgkin Lymphoma NHL. The study compares this treatment to a placebo plus SMT to determine its impact on infection rates. Participants are randomly assigned to one of two groups. One group receives a loading dose of XEMBIFY subcutaneously at 150 mgkgday for five consecutive days starting in Week 1, followed by biweekly doses of 300 mgkg until Week 51. The other group receives a placebo injection on the same schedule. Both groups continue to receive the standard medical treatments and supportive care they require throughout the study. During the study, participants will have regular assessments including monitoring the frequency of infections, hospitalizations, and antibiotic use. Researchers will measure the annual rate of major bacterial infections and track the time to first infection among other outcomes up to Week 51. Participants are observed closely throughout the treatment year to evaluate safety and effectiveness, with the entire study lasting approximately one year per participant.

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 III 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 IEQkg and three will receive 12,000 IEQkg, 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 the use of abatacept for treating 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 involves both pediatric and adult participants. The study aims to determine how effective abatacept is compared to a placebo in managing GLILD associated with CVID. Participants are divided into two groups based on weight and age. Pediatric subjects weighing less than 50 kg receive open-label abatacept with dosing based on weight, while pediatric subjects weighing 50 kg or more and adults are randomized in a 12 ratio to receive either abatacept or a placebo weekly for six months. After six months, all participants receive weekly abatacept treatment. Following the initial 12 months, patients may continue abatacept for up to three years, with safety monitoring every three months. Throughout the study, participants undergo various assessments including high-resolution chest CT scans at six months to measure lung changes. Additional tests such as lung function tests, quality of life questionnaires, steroid usage, infection monitoring, and pediatric growth measurements are performed at six and twelve months. Safety is closely monitored through reports of adverse events and infections. The total duration of participation may extend up to three years depending on continued treatment.

This research aims to understand how eosinophils, a type of white blood cell, become activated and their role in immune responses. Eosinophil counts often increase due to allergies, asthma, parasitic infections, autoimmune conditions, or rarely, tumors. Elevated eosinophil levels, called eosinophilia, usually cause no symptoms but can sometimes lead to swelling, itching, allergic lung problems, heart disease, or nerve damage. Participants with eosinophil counts over 750ml or abnormal eosinophil buildup in skin or tissues, aged 1 to 100 years, will undergo clinical evaluations including medical history, exams, and blood tests. Additional testing may include studies of eyes, lungs, skin, bone marrow, nerves, or heart depending on symptoms and age. This is an observational study without experimental treatments patients needing therapy will get standard care. Some participants may also undergo bone marrow biopsy, genetic testing, or leukapheresis for adults for research purposes. During the study, participants will donate blood samples for laboratory studies and may have annual follow-ups with exams and blood tests to track eosinophil levels and condition changes. Researchers will collect samples like blood, bone marrow, tissue, and body fluids to study disease mechanisms, biomarkers, and treatment responses. The study will monitor clinical and immunological responses to therapy and evaluate family members to explore genetic causes of eosinophilia. The main goal is to better understand eosinophilic disorders and improve diagnosis and treatment options.