Sporadic inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy presenting after age 50 years. It presents with chronic insidious proximal leg and distal arm asymmetric muscle weakness. Muscle histopathology reveals endomysial inflammatory exudates surrounding and invading non-necrotic muscle fibers often times accompanied by rimmed vacuoles and inclusions. Unlike polymyositis and dermatomyositis, patients with IBM do not improve with therapy; at present there is no effective treatment for IBM. The histopathological features and lack of response to immunotherapies has led many experts in the field to believe that IBM is primarily a degenerative disorder of muscle with secondary inflammation. We completed a randomized controlled pilot study in 24 IBM subjects, 18 of whom received arimoclomol 100 mg PO TID for four months and 8 were on placebo. Arimoclomol increases heat shock proteins and may prevent protein misfolding. We found arimoclomol to be safe. The IBM functional rating scale (IBMFRS) decline at 1 year was less in the arimoclomol group compared to placebo with the p value approaching significance at 8 months. We are therefore proposing a twenty months randomized, placebo-controlled Phase II study of arimoclomol in 150 IBM subjects. The primary aim is to assess the efficacy and safety of arimoclomol (200 mg TID). The primary efficacy endpoint is the IBMFRS. Secondary efficacy outcomes will include different measures of strength and function: manual muscle testing (MMT), maximum voluntary isometric contraction (MVICT) of quadriceps, grip and pinch test, modified timed up and go (mTUG), 6 minute walk test with 2 minute distance captured; a general physical function measure: Health Assessment Questionnaire (HAQ- DI); a Health-Related Quality of Life (HRQoL) measure using SF36. Safety laboratory and adverse events will be collected. Our long-term goal is to find an effective treatment for people with IBM.

Public Health Relevance

Sporadic inclusion body myositis (IBM) is the most common inflammatory myopathy after the age 50. It presents with proximal leg and distal arm muscle weakness. Currently, there is no effective treatment for IBM patients and patients will continue to get weak. Arimoclomol may slow down the process of protein misfolding and aggregation in IBM by helping the muscle fiber to up-regulate inducible heat shock proteins. It may also slow progression of muscle degeneration in this progressively debilitating disease. Should arimoclomol prove effective in slowing disease progression, it would have a long term impact on the functional ability of subjects with IBM.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project (R01)
Project #
5R01FD004809-02
Application #
9084426
Study Section
Special Emphasis Panel (ZFD1)
Project Start
2015-06-10
Project End
2021-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Kansas
Department
Type
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160