title: Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency.
abstract: Congenital factor XIII (FXIII) deficiency is a rare, autosomal-recessive disorder, with most patients having an A-subunit (FXIII-A) deficiency. Patients experience life-threatening bleeds, impaired wound healing, and spontaneous abortions. In many countries, only plasma or cryoprecipitate treatments are available, but these carry a risk for allergic reactions and infection with blood-borne pathogens. The present study was a multinational, open-label, single-arm, phase 3 prophylaxis trial evaluating the efficacy and safety of a novel recombinant FXIII (rFXIII) in congenital FXIII-A subunit deficiency. Forty-one patients ≥ 6 years of age (mean, 26.4; range, 7-60) with congenital FXIII-A subunit deficiency were enrolled. Throughout the rFXIII prophylaxis, only 5 bleeding episodes (all trauma induced) in 4 patients were treated with FXIII-containing products. The crude mean bleeding rate was significantly lower than the historic bleeding rate (0.138 vs 2.91 bleeds/patient/year, respectively) for on-demand treatment. Transient, non-neutralizing, low-titer anti-rFXIII Abs developed in 4 patients, none of whom experienced allergic reactions, any bleeds requiring treatment, or changes in FXIII pharmacokinetics during the trial or follow-up. These non-neutralizing Abs declined below detection limits in all 4 patients despite further exposure to rFXIII or other FXIII-containing products. We conclude that rFXIII is safe and effective in preventing bleeding episodes in patients with congenital FXIII-A subunit deficiency. This study is registered at http://www..clinicaltrials.gov as number NCT00713648.
authors.affiliation: Thrombosis and Hemostasis Unit, Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Aida
authors.initials: A
authors.lastname: Inbal
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Manuel
authors.initials: M
authors.lastname: Carcao
authors.forename: Anders
authors.initials: A
authors.lastname: Rosholm
authors.forename: Ramin
authors.initials: R
authors.lastname: Tehranchi
authors.forename: Diane
authors.initials: D
authors.lastname: Nugent
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D002648:Child; D004342:Drug Hypersensitivity / Q000209:etiology; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D012449:Safety
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII