title: PRTX-100 and methotrexate in patients with active rheumatoid arthritis: A Phase Ib randomized, double-blind, placebo-controlled, dose-escalation study.
abstract: PRTX-100 is a highly-purified preparation of staphylococcal protein A (SpA), with immunologic activity in vitro and in animal models of immune-mediated inflammation. Following single-dose healthy volunteer studies of safety and pharmacokinetics (PK), a multicenter, double-blind, placebo-controlled, sequential dose-escalation, repeated-dose phase I trial was conducted in patients with active rheumatoid arthritis (RA) on methotrexate therapy. Patients were randomized to receive either weekly intravenous PRTX-100 (0.15, 0.45, 0.90, or 1.50 µg/kg) or placebo for 4 weeks. Safety and disease activity were assessed over 16 weeks. Pharmacokinetic profiles were obtained after the first and fourth doses. The most common treatment-related adverse events were nausea, muscle spasms, dizziness, flushing, fatigue, RA flare, and headache. No serious adverse events were considered related to PRTX-100, and none occurred in the highest dose group. Geometric mean values for plasma Cmax (ng/mL) were 4.1, 15.7, 26.5, and 51.2 for doses of 0.15, 0.45, 0.90, and 1.5 µg/kg, respectively. Anti-drug antibodies (ADAs) developed in most PRTX-100 patients, but incidence and titer were not dose-dependent. At the two highest doses, data suggest PRTX-100 may have an effect on RA disease activity, even in patients with ADAs.
authors.affiliation: Protalex, Inc., Summit, NJ, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Bernton
authors.affiliation: Protalex, Inc., Summit, NJ, USA.
authors.forename: William
authors.initials: W
authors.lastname: Gannon
authors.affiliation: Kramer Consulting LLC, Rockville, MD, USA.
authors.forename: William
authors.initials: W
authors.lastname: Kramer
authors.affiliation: Parexel Clinical Pharmacology, Bloemfontein, South Africa.
authors.forename: Eduard
authors.initials: E
authors.lastname: Kranz
mesh_terms: D061605:Administration, Intravenous; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D013019:South Africa; D013205:Staphylococcal Protein A / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; D007073:Immunoglobulin E; D008727:Methotrexate
keywords: immunomodulator; phase I; rheumatoid arthritis; safety; staphylococcal protein A