Assessment of TRM-201 (Rofecoxib) Efficacy and Safety for Chronic Pain in Hemophilic Arthropathy: The Rofecoxib Efficacy and Safety Evaluation Trial in Hemophilic Arthropathy (RESET-HA), a Randomized, Double-Blind Placebo-Controlled Phase III Clinical Trial

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.4243-4243
• Main Authors: Boice, Judith A., Buckner, Tyler W., Croteau, Stacy E., Katz, Nathaniel, Sidonio, Robert F., Mauer, Kim, Bolognese, James, Garfield, Mary, Corrigon, Mark, Walsh, Christopher E
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-154056

Background: Intra-articular bleeding (hemarthrosis) accounts for 80-90% (Roosendaal, et. al. Semin Thromb Hemost . 2003;29:37) of all bleeds and more than 90% of serious bleeding events in patients with severe hemophilia (Valentino. J Thromb Haemost . 2010;8:1895). Recurrent hemarthroses result in progressive joint damage and the development of hemophilic arthropathy (HA) in up to 50% of adults with hemophilia (Forsyth, et al. Haemophilia . 2014;20:44). Acetaminophen is commonly prescribed for pain due to HA yet has limited efficacy at therapeutic doses (Rodriguez-Merchan. Blood Rev. 2018;32:116). Traditional non-steroidal anti-inflammatory drugs (tNSAIDs) inhibit platelet function and cause gastrointestinal (GI) complications including bleeding, both of which can be harmful in patients with hemophilia (Rodriguez-Merchan. Blood Rev. 2018;32:116; Brooks, et al. Rheumatology . 1999;38(8):779). Opioids are prescribed in over 60% of patients with HA(Witkop, et al. Haemophilia. 2012;18:e115) despite dependence, potential for abuse, and an increased risk of falls and other opioid-related injury (Rodriguez-Merchan. Blood Rev. 2018;32:116). Given an unmet need in pain management for HA, alternate approaches are needed. TRM-201 (rofecoxib) is a cyclooxygenase-2 (COX-2) selective NSAID with no impact on platelet function and a lower GI risk than tNSAIDs (Vioxx (rofecoxib) package insert. Merck & Co. I, ed. Whitehouse Station, NJ, 2004). The RESET-HA study is designed to evaluate the efficacy and safety of rofecoxib for HA pain management. Methods/Design: RESET-HA is a multi-national, randomized, double-blind study to evaluate the efficacy and safety of rofecoxib in hemophilia A or B patients with diagnosed HA, aged 12 to 75 years and is based on a previous pilot study (Tsoukas, et al. Blood, 2006;107:1785). Patients must have a history of joint bleeding, and chronic symptomatic pain in one or more joint(s) on 20 of the 30 days prior to screening. Exclusion criteria include use of opioids for greater than 4 days/week, or opioid transdermal patches in the 30 days prior to screening, history of GI perforation, ulcer or bleeding, peptic ulcer disease and major cardiac ischemic symptoms or events. Randomized patients (n=80 per arm) are washed out of analgesics prior to daily administration of TRM-201 (17.5 mg/day) or placebo for 12 weeks (Part I) during which acetaminophen (Stage-1) and acetaminophen plus codeine (Stage-2) are available as rescue medication (where availa