Natalizumab in Inclusion Body Myositis (IBM)

Study Overview
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Brief Summary
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Muscle biopsies of patients with Inclusion Body Myositis (IBM) have demonstrated a T-cell predominant inflammatory infiltrate, therefore, new agents targeting T -cell mediated cell death may be a novel treatment for IBM. Such an agent capable of preventing T-cell movement out of the vasculature, such as natalizumab, may be beneficial in IBM patients. Six patients will be recruited to participate in this phase I trial.

Detailed Description
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This is a phase I open label, non-placebo controlled trial evaluating the safety and efficacy of natalizumab in patients with IBM. Pre and post treatment muscle biopsies including measurements of the degree of inflammation as well as the types of inflammatory cells will be measured. The investigators will also assess quality of life, the inclusion body myositis functional rating score (IBM-FRS), and patient and physician global impression of change. Manual muscle testing and quantitative dynamometry will also be evaluated to see if patient's strength improves. Patients who are eligible to participate and have signed a consent form will have a muscle biopsy performed at baseline and at the end of the study. Physical and neurological exams, as well as IBM-FRS, safety labs will be conducted and collected at monthly visits. Patients will start natalizumab therapy at 300mg intravenously every 4 weeks for 24 weeks. All study related procedures will be conducted at Phoenix Neurological Associates, as well as all infusions and muscle biopsies

Official Title
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Pilot Study of Natalizumab in the Treatment of Patients With Inclusion Body Myositis

Conditions
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Inclusion Body Myositis (IBM)

Intervention / Treatment
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* Drug: Natalizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Definite diagnosis of sporadic IBM through previous muscle biopsies Age 21-85 FVC> 50% Muscle function adequate for quantitative muscle testing JC virus negative at screening Exclusion Criteria: Previous therapy with natalizumab. Treatment with other immunosuppressive agents within the last 12 months Quadriceps strength less than or equal to 2/5 at baseline Known malignancy Pregnancy or breastfeeding History of abnormal laboratory results indicative of any significant medical disease that would preclude the use of natalizumab Any clinically significant infectious illness in the 30 days before enrollment

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Natalizumab<br>Natalizumab therapy will be given at 300mg intravenously every 4 weeks for 24 weeks | Drug: Natalizumab<br> <br> * Other names: Tysabri;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine if natalizumab is effective and safe in the treatment of patients with IBM (muscle biopsies) | muscle biopsies to determine inflammation | 12 months | 
| Determine if natalizumab is effective and safe in the treatment of patients with IBM (manual muscle testing) | MMT - manual muscle testing to determine strength | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcome measures will involve an assessment of pre and post treatment muscle biopsies including measurements of the degree of inflammation as well as the types of inflammatory cells. (blood levels) | Safety labs - to determine blood levels | 12 months | 
| Secondary outcome measures will involve an assessment of pre and post treatment muscle biopsies including measurements of the degree of inflammation as well as the types of inflammatory cells. (pain scores) | Pain scores on a visual analog scale | 12 months | 
| Secondary outcome measures will involve an assessment of pre and post treatment muscle biopsies including measurements of the degree of inflammation as well as the types of inflammatory cells. (functional rating score scale) | IM-FRS a functional rating score scale | 12 months |