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PRTX‐100 and methotrexate in patients with active rheumatoid arthritis: A Phase Ib randomized, double‐blind, placebo‐controlled, dose‐escalation study
Author(s) -
Bernton Edward,
Gan William,
Kramer William,
Kranz Eduard
Publication year - 2014
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.116
Subject(s) - medicine , rheumatoid arthritis , adverse effect , pharmacokinetics , placebo , methotrexate , nausea , cmax , arthritis , gastroenterology , pharmacology , alternative medicine , pathology
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 C max (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.