SAN FRANCISCO, CA—Fasitibant did not reduce pain in patients with symptomatic osteoarthritis (OA) of the knee; however, the 5mg dose was associated with significantly less use of rescue medication, suggesting indirect evidence of efficacy, according to results of a Phase 2, double-blind randomized dose-finding study reported at the 2015 ACR/ARHP Annual Meeting.
Fasitibant, a competitive, potent, and selective antagonist of the bradykinin B2 receptor, is administered intra-articularly (IA) for symptomatic knee OA. Positive outcomes from a previous exploratory randomized clinical trial led Claudia Gabriele Werner, PhD, Clinical Research Department, Menarini Research & Business Service GmbH, Berlin, Germany, and colleagues to evaluate fasitibant given at three different doses vs. placebo.
The study, conducted at 25 European and US clinical sites, randomly assigned 431 patients with moderate to severe symptomatic knee OA to fasitibant 1mg (n=108), 2.5mg (n=108), 5mg (n=107), or placebo (n=108).
The primary endpoint was change in pain intensity, evaluated using the visual analog Western Ontario and McMaster Universities (WOMAC) osteoarthritis index A (total pain) subscore from baseline over two weeks post-treatment.
“Secondary measures included WOMAC Index, WOMAC stiffness (B) and functional impairment (C) subscores, pain at rest, pain after 15 meters walk (100mm VAS) and patient global assessment (PGA) scores,” the investigators reported.
Safety assessments included lab test monitoring, vital signs, ECG, physical examinations (including the target knee), adverse events, and rescue medication use.
At Week 1 and Week 2 following single IA injections of fasitibant or placebo, all treatments showed a decrease in WOMAC A pain, with no fasitibant group significantly discriminating the index score compared with placebo. Time to first use of rescue medication discriminated the fasitibant 5mg dose group significantly from placebo (P<0.0154).
“Fasitibant was well tolerated,” they reported, with no serious adverse events.
The majority of TESSs were mild or moderate, with severe TESSs occurring in 12 patients (2.8%). Among TESSs observed, 29 were considered treatment-related, 13 of which were in the placebo group.
“Lab tests, ECGs, and vital signs were in general unremarkable and similar between treatments,” Dr. Werner reported.
“The very high placebo response as well as the long duration of OA-symptoms (8.5±7.06 years) in all treatment groups may have contributed to the lack of efficacy as reported for other randomized controlled trials in patients with symptomatic knee OA,” they concluded. “Fasitibant was in general safe and local tolerability at the target knee was good.”