Patients’ characteristics and adverse events.
anaphylactic reaction, neurodegenerative disease, choking, vomiting, pyrexia, TEAEs, vomiting, rash, SAEs, pyrexia, infection, angioedema, headache, deaths, hypersensitivity, vomiting, listlessness
ANAPHYLACTIC REACTION, NEURODEGENERATIVE DISEASE, ADVERSE EVENTS, CSF PLEOCYTOSIS, EVENT, UPPER RESPIRATORY TRACT INFECTION, WOUND INFECTION, COMPLICATIONS, EVENTS, CHOKING, BLOOD, INFECTION, ADVERSE EVENT, ANGIOEDEMA, CSF LEAKAGE, HYPERSENSITIVITY, SUBDURAL HYGROMA
Interventional Study 250-201 was divided into Part 1 and Part 2 (Patient 9001 in Study 250-201 Part 1 received 28 weekly doses at 30 mg of tralesinidase alfa, followed by 10 doses at 100 mg, and then 11 doses at 300 mg before being recruited to Study 250-201 Part 2. Patient 9002 received 8, 10, and 19 doses of 30, 100, and 300 mg tralesinidase alfa, respectively, before being recruited to Study 250-201 Part 2, whereas patient 9003 received 20, 10, and 9 doses of 30, 100, and a 300 mg dose of tralesinidase alfa in Study 250-201 Part 1.Characteristics of the participants in Study 250-201 Part 2 are summarized in No deaths occurred during the course of the study. One participant discontinued the study following a serious adverse event (SAE) of subdural hygroma associated with increased intracranial pressure occurring after the seventh dose of tralesinidase alfa. This event was considered common terminology criteria for adverse events (CTCAE) grade 3 and was assessed as unrelated to the study drug or the device by the site’s principal investigator. Clinical symptoms (headache, vomiting, listlessness) resolved within 24 hours with medical management. In total, this patient received only 8 doses of tralesinidase alfa. The most common treatment-emergent adverse events (TEAEs) included vomiting, pyrexia, upper respiratory tract infection, headache, and CSF pleocytosis. SAEs assessed by investigators to be related to the study drug were CSF pleocytosis, vomiting, angioedema, fluctuating consciousness, and pyrexia. SAEs assessed by investigators to be related to the i.c.v. device were infection, device malfunction, CSF leakage, and wound infection. Overall, these TEAEs and SAEs were consistent with known complications of enzyme replacement therapy (ERT), i.c.v. devices, and/or neurodegenerative disease in pediatric populations.Eight hypersensitivity events were reported for 5 patients, 5 events of rash, and 1 event each of angioedema, choking, and maculopapular rash. Blood samples for total IgE, C4, serum tryptase, and drug-specific IgE did not show evidence of anaphylactic reaction in any of these 5 patients for any of the hypersensitivity events observed.