Pediatric blood & cancer · 2026
Sustained Therapeutic Efficacy of Intravenous Plasminogen Concentrate in Pediatric Patients With Type 1 Plasminogen Deficiency: An Analysis of Dosing Parameters and Clinical Outcomes.
СтатьяКлиническое исследование II фазыКлиническое исследование III фазыНазвание и аннотация: Перевод в очереди
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Nakar Charles, Thibaudeau Karen, Mathias Mary, McDaniel Heather, Reschke Madlen, Tenbrock Klaus, Parker Joseph M, Shapiro Amy
Аннотация
BACKGROUND: Type 1 plasminogen deficiency (PLGD-1) is an ultra-rare autosomal recessive disorder caused by variants in the PLG gene and affects approximately 1.6 individuals per million. The condition is characterized by decreased plasminogen levels and impaired function, resulting in fibrin-rich lesions on mucous membranes throughout the body. Pediatric patients often experience earlier symptoms than adults, including more severe life-threatening complications such as airway obstruction and hydrocephalus.
PROCEDURE: This analysis describes 17 pediatric patients (ages 11 months to 16 years) with PLGD-1 treated with intravenous (IV) plasminogen concentrate enrolled in the Phase 2/3 pivotal trial (NCT02690714), long-term study (NCT03642691), and expanded access and compassionate use programs of IV plasminogen concentrate at a dose of 6.6 mg/kg at intervals ranging from daily to once every 35 days.
RESULTS: Baseline plasminogen activity ranged from <2% to 40% (median: 27%). All patients (N = 11) in the compassionate use and expanded access programs, and half of those in the pivotal trial (3/6), had at least one lesion at enrollment. Of those with lesions, the most common were conjunctival (79%) and respiratory (43%). IV plasminogen concentrate therapy elevated plasminogen levels, resulting in lesion resolution across anatomical locations. Pharmacokinetic evidence confirmed that therapeutic plasminogen levels were achieved and maintained in children, providing the foundation for effective reduction and/or resolution of extravascular lesions.
CONCLUSIONS: IV plasminogen concentrate is a systemic targeted therapy for PLGD-1 that addresses the underlying biochemical defect and enables sustained fibrinolysis and lesion clearance. Early recognition and prompt treatment are critical to preventing permanent morbidity or mortality.
TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02690714 (Phase 2/3 pivotal trial) and NCT03642691 (long-term study).
PROCEDURE: This analysis describes 17 pediatric patients (ages 11 months to 16 years) with PLGD-1 treated with intravenous (IV) plasminogen concentrate enrolled in the Phase 2/3 pivotal trial (NCT02690714), long-term study (NCT03642691), and expanded access and compassionate use programs of IV plasminogen concentrate at a dose of 6.6 mg/kg at intervals ranging from daily to once every 35 days.
RESULTS: Baseline plasminogen activity ranged from <2% to 40% (median: 27%). All patients (N = 11) in the compassionate use and expanded access programs, and half of those in the pivotal trial (3/6), had at least one lesion at enrollment. Of those with lesions, the most common were conjunctival (79%) and respiratory (43%). IV plasminogen concentrate therapy elevated plasminogen levels, resulting in lesion resolution across anatomical locations. Pharmacokinetic evidence confirmed that therapeutic plasminogen levels were achieved and maintained in children, providing the foundation for effective reduction and/or resolution of extravascular lesions.
CONCLUSIONS: IV plasminogen concentrate is a systemic targeted therapy for PLGD-1 that addresses the underlying biochemical defect and enables sustained fibrinolysis and lesion clearance. Early recognition and prompt treatment are critical to preventing permanent morbidity or mortality.
TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02690714 (Phase 2/3 pivotal trial) and NCT03642691 (long-term study).