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LB0002 Safety and Tolerability of Arimoclomol in Patients with Sporadic Inclusion Body Myositis: A Randomised, Double-Blind, Placebo-Controlled, Phase IIa Proof-of-Concept Trial
  1. P. Machado1,
  2. A. Miller1,
  3. L. Herbelin2,
  4. J. He2,
  5. J. Noel2,
  6. Y. Wang2,
  7. A. L. McVey2,
  8. M. Pasnoor2,
  9. P. Gallagher2,
  10. J. Statland3,
  11. S. Brady1,
  12. C.-H. Lu1,
  13. B. Kalmar1,
  14. H. Sethi1,
  15. G. Samandouras1,
  16. J. Holton1,
  17. L. Greensmith1,
  18. R. J. Barohn2,
  19. M. G. Hanna1,
  20. M. M. Dimachkie2
  1. 1MRC Centre for Neuromuscular Diseases, University College London, London, United Kingdom
  2. 2Neurology, The University of Kansas Medical Center, Kansas City
  3. 3Neurology, The University of Kansas, Lawrence, United States


Background Sporadic inclusion body myositis (IBM) is the commonest idiopathic inflammatory myopathy occurring in patients over the age of 50 years. IBM muscle displays inflammatory and degenerative features. Previous trials have only involved agents directed purely at the inflammatory component of IBM pathology and all were ineffective. Modulating the cytoprotective “heat shock response” (HSR) represents a therapeutic strategy through which the detrimental aspects of both inflammation and degeneration could be dampened. Arimoclomol is an orally administered pharmacological agent that can up-regulate the HSR by amplifying heat shock protein (HSP) expression.

Objectives To evaluate the safety and tolerability of arimoclomol in IBM and to gather exploratory efficacy data of arimoclomol in IBM.

Methods In this double-blind, placebo-controlled, two-centre (London, UK and Kansas, USA), phase IIa study, 24 patients with IBM were randomised to arimoclomol 100mg TID or placebo (2:1 ratio) over 4 months (as mandated by the FDA), followed by an 8 month follow up period. The primary outcome was adverse event reporting (safety and tolerability). Measures of physical function (IBM functional rating scale (IBMFRS)), muscle strength (manual muscle testing (MMT) and maximum isometric contraction testing (MVICT)) and fat-free mass percentage (measured by dual-energy X-ray absorptiometry (DEXA)) were included as secondary outcome measures. HSP70 levels in muscle biopsy tissue (adjusted to myosin content) before and after the treatment phase were also measured. Mann-Whitney U test was used to compare changes in the arimoclomol and placebo groups at 4 months (IBMFRS, MMT, MVICT, DEXA and HSP70), 8 months (IBMFRS, MMT and MVICT) and 12 months (IBMFRS, MMT, MVICT and DEXA).

Results We enrolled 17 men and 7women with a mean age of 66.8±7.5 years and mean disease duration of 8.4±4.3 years. All patients fulfilled the Griggs criteria for definite (42%) or probable (58%) IBM. One serious adverse event was observed in the arimoclomol group (hypertension requiring prolonged hospitalization on the day of the first biopsy). One arimoclomol recipient developed transient hyponatremia. Ophthalmologic examination did not reveal any significant ocular morbidity. Overall, the safety and tolerability profiles were similar between groups. At 8 months, we detected a trend of slower decline in the IBMFRS (-0.68±1.58 vs -2.50±3.31, p=0.055), average MMT (-0.12±0.22 vs -0.26±0.27, p=0.147) and MVICT of right hand grip (1.26±2.63 vs -0.54±1.86, p=0.064) of the arimoclomol group but no differences were seen for changes in the other MVICT scores (left hand grip, left and right quadriceps, and total sum score), DEXA fat free mass percentage and HSP70 levels in the muscle tissue.

Conclusions Arimoclomol was safe and well tolerated and demonstrated a preliminary signal for potential therapeutic benefit in patients with IBM. These data support further research of arimoclomol in IBM.

Acknowledgements This investigator-initiated trial was funded by Arthritis Research UK, Kansas University Neurology Ziegler Grant and Kansas University General Clinical Research Centre CReFF Grant.

Disclosure of Interest None Declared

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