Study of Arimoclomol in Inclusion Body Myositis (IBM)

Study Overview
=================
Brief Summary
-----------------
Funding Source - FDA Office of Orphan Products Development (OOPD). The purpose of this study is to evaluate the safety and efficacy of the study drug, arimoclomol in IBM patients.

Detailed Description
-----------------
A Phase 2/3, randomized, double-blind, placebo-controlled, international, 20-month intervention study in patients with IBM.

Official Title
-----------------
Phase II Study of Arimoclomol for the Treatment of Sporadic Inclusion Body Myositis (IBM)

Conditions
-----------------
Inclusion Body Myositis

Intervention / Treatment
-----------------
* Drug: Arimoclomol
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meet any of the European Neuromuscular Centre Inclusion Body Myositis research diagnostic criteria 2011 categories for IBM. Demonstrate being able to arise from a chair without support from another person or device. Able to ambulate at least 20 ft/6 meters with or without assistive device. Once arisen from the chair, participant may use any walking device, i.e. walker/frame, can, crutches, or braces. They cannot be supported by another person and cannot use furniture or wall for support. Age at onset of weakness >45 years. Body weight of >= 40 kg. Able to give informed consent. Exclusion Criteria: History of any of the following excludes subject participation in the study: chronic infection particularly HIV or Hepatitis B or C; cancer other than basal cell cancer less than five years prior; or other chronic serious medical illnesses. Presence of any of the following on routine blood screening: White blood cells (WBC) <3000; platelets < 100,000; hematocrit <30%; blood urea nitrogen (BUN) >30 mg/dL; creatinine >1.5 x upper limit of normal; symptomatic liver disease with serum albumin <3 g/dL. History of most recent creatine kinase >15x the upper limit of normal without any other explanation besides IBM. History of non-compliance with other therapies. Use of testosterone except for physiologic replacement doses in case of androgen deficiency. Participants must have documented proof of the androgen deficiency. Coexistence of other disease that would be likely to affect outcome measures Drug or alcohol abuse within past three months. Participation in a recent drug study in the last 30 days prior to the screening visit or use of a biologic agent less than 6 months prior to the screening visit. Women who are lactating or unwilling to use adequate method of birth control who are not surgically sterile. Adequate birth control includes use of intrauterine device, abstinence, or oral contraceptives or a double barrier method, e.g condom plus diaphragm will be necessary for both male and female participants. Participants taking >7.5 mg prednisolone or equivalent or participants on Intravenous Immunoglobulin Therapy (IVIg) or other immunosuppressants within the last 3 months. Clinically significant renal or hepatic disease, as indicated by clinical laboratory assessment.

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arimoclomol<br>248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily | Drug: Arimoclomol<br>* 2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily during breakfast, early afternoon, and at bedtime<br>|
| Placebo Comparator: Placebo<br>248 mg matching placebo 3 times daily | Other: Placebo<br>* 2 matched placebo capsules taken 3 times daily during breakfast, early afternoon, and at bedtime<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | Measured by rate of decline in the IBMFRS between experimental and placebo groups. The IBMFRS is a 10-item questionnaire. Scores for each item range from 0 to 4. There is a total maximum score of 40 and minimum score of 0. The higher the score the better functional status of the person. | Change from Baseline to Month 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | Measured by rate of decline in the IBMFRS between experimental and placebo groups. The IBMFRS is a 10-item questionnaire. Scores for each item range from 0 to 4. There is a total maximum score of 40 and minimum score of 0. The higher the score the better functional status of the person. | Change from Baseline to Month 12 | 
| Grip Strength | Unilateral hand grip strength in both hands measured using the Jamar Dynamometer. Results are for the stronger limb, as identified at baseline. | Change from Baseline to Month 12 and 20 | 
| Modified Timed up and go (mTUG) | The patient's combined ability to rise from a chair and walk 3 meters, turn around and walk back to the chair and sit down. The test was performed twice and the fastest time was used. The results were expressed as velocity in meters/second. | Change from Baseline to Month 12 and Month 20 | 
| Manual Muscle Testing (MMT), Total Score | The Manual Muscle Testing (MMT) scores the strength of 24 muscles (axial, proximal, and distal muscles, tested bilaterally) on a scale from 0 to 10 points. The total score is calculated as an average across the 24 muscles and ranges from 0 to 10. The total score will increase if a patient is getting stronger and decrease if a patient is getting weaker. | Change from Baseline to Month 12 and Month 20 | 
| 6 Minute Walk Test (6MWT); Distance After 6 Minutes (6MWD) | The distance patients could walk in 6 minutes. The distance walked in meters was recorded after 6 minutes. | Change from Baseline to Month 12 and Month 20 | 
| Short Form-36 (SF-36) Physical Component Score | Measured using the Short Form health survey with 36 items (SF-36). The questionnaire measures 8 health concepts which yields 2 summary measures: physical and mental health. The physical component score includes 4 scales of physical functioning (10 items), role limitations due to physical health (4 items), bodily pain (2 items), and general health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100, and the summary measure is calculated as the average score. Higher scores indicate better health status. | Change from Baseline to Month 12 and Month 20 | 
| Maximum Voluntary Isometric Contraction (MVICT) of Quadriceps | Unilateral strength of the knee extensor muscles on both limbs using the MicroFET hand-held dynamometer. Results are for the stronger limb, as identified at baseline. | Change from Baseline to Month 12 and Month 20 | 
| Health Assessment Questionnaire - Disability Index (HAQ-DI) | The disability index of the HAQ measures self-reported functional status (disability) including the patient's use of aids or devices and/or help from other persons. The scale is composed of 20 items in 8 domains (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities). Each domain has at least 2 subcategory items, scored on a scale from 0 to 3, and for each of the 8 domains the domain score was the highest score of the involved subcategory scores. The total score reported is an average over 8 domains and scores from at least 6 domains had to be available for the total score to be calculated. The average total score ranges from 0 to 3, and a higher score corresponds to a worsening in functional status. | Change from Baseline to Month 12 and Month 20 | 
| 2 Minute Walk Test (2MWT) | The distance patients could walk in 2 minutes (during the 6 Minute Walk Test) recorded in meters. | Change from Baseline to Month 12 and Month 20 | 
| Short Form-36 (SF-36) Mental Component Score | Measured using the Short Form health survey with 36 items (SF-36). The questionnaire measures 8 health concepts which yields 2 summary measures: physical and mental health. The mental component score is composed of energy/fatigue (4 items), social functioning (2 items), role limitations due to emotional problems (3 items), and emotional well-being (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100, and the summary measure is calculated as the average score. Higher scores indicate better health status. | Change from Baseline to Month 12 and Month 20 | 
| Patient Global Impression of Severity (PGIS) | Patient-reported assessment of the impact of IBM on the ability to complete activities of daily living (e.g. dressing, walking, bathing) at the time of the assessment. The response options for the impact of IBM were none (i.e. no impact), very mild, mild, moderate, severe, and very severe. | Change from Baseline to Month 12 and Month 20 | 
| Patient Global Impression of Change (PGIC) | Patient-reported assessment of the change from start of study treatment in the impact of IBM on the ability to complete activities of daily living (e.g. dressing, walking, bathing). The response options for change in impact were very much worse, much worse, a little worse, no change, a little improved, much improved, and very much improved. | Change from Baseline to Month 12 and Month 20 | 
| Clinician Global Impression of Severity (CGIS) | Clinician-reported assessment of the severity of the patient's IBM symptoms at the time of the assessment. The response options were none, very mild, mild, moderate, severe, and very severe | Change from Baseline to Month 12 and Month 20 | 
| Clinician Global Impression of Change (CGIC) | Clinician-reported assessment of the change from start of study treatment in the patient's IBM symptoms. The response options for change in IBM were very much worse, much worse, a little worse, no change, a little improved, much improved, and very much improved. | Change from Baseline to Month 12 and Month 20 | 
| Falls and Near Falls | Falls and near falls registered by the participants in a diary | Accumulated number from Baseline to Month 20 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IBM