A Randomized, Double-blind, Placebo-controlled Study of Arimoclomol in Patients with Inclusion Body Myositis

Pedro Machado¹, Richard Barohn², Michael McDermott³, Thomas Blaetter⁴, Tom Lloyd⁵, Aziz Shaibani⁶, Miriam Freimer⁷, Anthony Amato⁸, Emma Ciafaloni³, Sarah Jones⁹, Tahseen Mozaffar¹⁰, Summer Gibson¹¹, Matthew Wicklund¹², Todd Levine¹³, Claus Sundgreen⁴, Tim Carstensen⁴, Karen Bonefeld⁴, Anders Jørgensen⁴, Karina Phonekeo⁴, Andrew Heim¹⁴, Laura Herbelin¹⁴, Michael Hanna¹⁵ and Mazen Dimachkie¹⁴, ¹Centre for Rheumatology & Department of Neuromuscular Diseases, University College London, London, United Kingdom, ²University of Missouri - Columbia, Columbia, MO, ³University of Rochester, Rochester, NY, ⁴Orphazyme A/S, Copenhagen, Denmark, ⁵Johns Hopkins University, Baltimore, MD, ⁶Nerve and Musle Center, Houston, TX, ⁷Ohio State University, Columbus, OH, ⁸Brigham and Women's Hospital, Boston, MA, ⁹University of Virginia, Charlottesville, VA, ¹⁰University of California Irvine, Irvine, CA, ¹¹University of Utah, Salt Lake City, UT, ¹²University of Colorado, Denver, CO, ¹³Phoenix Neurological Associates, Phoenix, AZ, ¹⁴University of Kansas Medical Center, Kansas City, KS, ¹⁵University College London, London, United Kingdom

Meeting: ACR Convergence 2021

Keywords: clinical trial, Myopathies, Myositis, Outcome measures, Randomized Trial

Session Information

Date: Saturday, November 6, 2021

Title: Abstracts: Muscle Biology, Myositis & Myopathies (0441–0444)

Session Type: Abstract Session

Session Time: 9:00AM-9:15AM

Background/Purpose: Inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy occurring in patients over the age of 45 years. Since immune suppression has not been effective, modulating the cytoprotective “heat shock response” (HSR) represents a candidate therapeutic approach targeting both inflammation and degeneration. In a pilot study, arimoclomol, an amplifier of the HSR, was safe and well tolerated with some trends suggesting efficacy at 8 months in subjects with IBM. Our aim is to present the efficacy and safety/tolerability data from a phase 2/3 randomized controlled trial of arimoclomol in IBM (NCT02753530).

Methods: In this international multicenter, double-blind, placebo-controlled trial, subjects were randomized (1:1) to receive either arimoclomol citrate 400 mg or matching placebo capsules three times a day (1,200 mg/day) for 20 months. The primary outcome measure was the change from baseline to Month 20 in the IBM Functional Rating Scale (IBMFRS) total score. Hierarchically ordered key secondary outcome measures included hand grip strength (strongest hand), Modified Time Up and Go, Manual Muscle Testing (24 muscles), 6-minute walk test distance, and the Short-Form 36 health survey. Other outcome measures included patient and clinician impressions, and other measures of muscle strength and function. Drug safety and tolerability were evaluated.

Results: One hundred fifty-two IBM subjects fulfilling ENMC 2011 criteria were randomized with mean age 67.2 years (SD 8.1), mostly men (76%), mean disease duration 98 months (SD 58), and mean baseline IBMFRS of 27.4 (SD 4.6). The IBMFRS declined by a mean of 3.25 points with arimoclomol vs. 2.26 points with placebo over 20 months (p=0.11). Secondary efficacy outcome measures did not show any statistically significant treatment group differences. Most frequently reported AEs observed with higher incidence in arimoclomol group were gastrointestinal disorders (54.8% vs. 39.7%). Patients receiving arimoclomol were more likely to discontinue treatment due to AEs (17.8% vs. 5.1%). The relative frequency of serious AEs was comparable in the two treatment arms (arimoclomol 15.1% vs. placebo 23.1%). Elevated transaminases were reported in the first three months and were more frequently observed with arimoclomol than with placebo (15.4% vs. 6.4%).

Conclusion: This trial did not demonstrate a benefit of arimoclomol in IBM with respect to its primary and secondary efficacy endpoints.

Disclosures: P. Machado, Abbvie, 6, BMS, 6, Celgene, 6, Eli Lilly, 2, Janssen, 2, MSD, 6, Galapagos, 6, Novartis, 2, 6, Pfizer, 6, Roche, 6, UCB, 2, 6, Orphazyme, 5, 6; R. Barohn, Orphazyme, 2, Orphazyme, 5; M. McDermott, Orphazyme, 5; T. Blaetter, Orphazyme, 3; T. Lloyd, Orphazyme, 5; A. Shaibani, Orphazyme, 5; M. Freimer, Orphazyme, 5; A. Amato, Orphazyme, 5; E. Ciafaloni, Orphazyme, 5; S. Jones, Orphazyme, 5; T. Mozaffar, None; S. Gibson, Orphazyme, 5; M. Wicklund, Orphazyme, 5; T. Levine, None; C. Sundgreen, Orphazyme, 3; T. Carstensen, Orphazyme, 3; K. Bonefeld, Orphazyme, 3; A. Jørgensen, Orphazyme, 3; K. Phonekeo, Orphazyme, 3; A. Heim, Orphazyme, 5; L. Herbelin, Orphazyme, 2, 5; M. Hanna, Orphazyme, 2, 5; M. Dimachkie, Octapharma, 2, 5, CSL-Behring, 2, 5, Orphazyme, 2, 5, Kezar, 1, 2, 5, UCB, 1, 2, 5, Shire Takeda, 2, 5, Bristol-Myers Squibb, 5, Corbus, 5, FDA/OOPD, 5, IMACS, 4.

To cite this abstract in AMA style:

Machado P, Barohn R, McDermott M, Blaetter T, Lloyd T, Shaibani A, Freimer M, Amato A, Ciafaloni E, Jones S, Mozaffar T, Gibson S, Wicklund M, Levine T, Sundgreen C, Carstensen T, Bonefeld K, Jørgensen A, Phonekeo K, Heim A, Herbelin L, Hanna M, Dimachkie M. A Randomized, Double-blind, Placebo-controlled Study of Arimoclomol in Patients with Inclusion Body Myositis [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/a-randomized-double-blind-placebo-controlled-study-of-arimoclomol-in-patients-with-inclusion-body-myositis/. Accessed .

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