title: First-in-human study with new recombinant agalsidase beta (ISU303) in healthy subjects.
abstract: ISU303 is a new recombinant agalsidase beta (Agal) enzyme replacement therapy under investigation for Fabry disease, caused by a deficiency in α-galactosidase A activity that leads to fatty deposits in tissues. We evaluated the pharmacokinetic (PK) parameters, safety and tolerability of ISU303 in healthy adult volunteers. The study was a dose block-randomized, double-blinded, placebo-controlled, single-dosing, and dose escalation phase 1 clinical trial. A total of 18 healthy subjects were enrolled (0.3 mg/kg, n = 6; 1.0 mg/kg, n = 6; placebo, n = 6). Blood samples for PK analysis were collected according to planned time. The PK parameters in each 0.3 and 1.0 mg/kg Agal group were as follows: Cmax (mU/mL) 43.19 ± 5.9 and 195.86 ± 32.3; AUClast (h·mU/mL) 207.91 ± 25.1 and 939.96 ± 158.3; t1/2 (hours) 1.13 ± 0.3 and 1.46 ± 0.2; Cl (mL/min/kg) 1.79 ± 0.2 and 1.34 ± 0.2, respectively. There were seven adverse events (AE) overall. All AEs were resolved without any complications. None were related to the study drug. There were no immunogenicity or any significant infusion-related reactions. The new Agal product exhibited a dose-dependent PK and was well tolerated with no significant AEs in healthy adult volunteers.
authors.affiliation: Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: Choon O K
authors.initials: CO
authors.lastname: Kim
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Oh
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Park
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007527:Isoenzymes / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics; D055815:Young Adult; D000519:alpha-Galactosidase / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*
chemical_list: D007074:Immunoglobulin G; D007527:Isoenzymes; D011994:Recombinant Proteins; D000519:alpha-Galactosidase; C459420:agalsidase beta
keywords: agalsidase beta; pharmacokinetics; safety