Efficacy and Tolerability of BAF312 in Patients With Polymyositis and Dermatomyositis

Study Overview
=================
Brief Summary
-----------------
This study determined the efficacy, safety, tolerability and the PK profile of BAF312, a novel immunomodulator, in polymyositis and dermatomyositis patients who were not responsive to traditional immunosuppressive and/or corticosteroid therapy. The study consisted of a 12 week, randomized, placebo controlled period, followed by another 12 weeks where all subjects received BAF312 treatment.

Official Title
-----------------
A Multi-centre, Double-blind, Placebo Controlled, Proof of Concept Study to Evaluate the Efficacy and Tolerability of BAF312 in Patients With Polymyositis and Dermatomyositis

Conditions
-----------------
Polymyositis, Dermatomyositis

Intervention / Treatment
-----------------
* Drug: BAF312
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with disease at least 3 months before study Muscle weakness Received corticosteroids with or with out disease modifying antirheumatic drugs at least 3 months before study however not responding to this therapy Exclusion Criteria: Other idiopathic inflammatory myopathies Myopathy other than polymyositis and dermatomyositis Patients with late stages of disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Experimental: BAF312<br> | Drug: BAF312<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Responded to BAF312 | Preliminary clinical efficacy of BAF312 in patients with Polymyositis and dermatomyositis (PM/DM) using the International Myositis Assessment and Clinical Studies Group (IMACS) core set measures (including manual muscle testing, Physician's Global Activity Assessment (on a horizontal 10 cm visual analogue scale), Patient Global Activity Assessment (on a horizontal 10 cm visual analogue scale), Physical Function (Health Assessment Questionnaire), Muscle-associated Enzymes (CK, LDH, AST, ALT, aldolase) and Extra-Muscular Activity Assessment (Extra-muscular portion of Myositis Disease Activity Assessment Tool). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Change in Steroids Use After BAF312 Administration -Period 2 |  | 12 weeks | 
| Mean Plasma Concentrations of BAF312 |  | baseline to end of trial (day 196) | 
| Summary of CRP Levels | Biomarkers reflecting efficacy in reducing systemic inflammatory components of the disease using serum markers such as C-reactive protein (CRP) | 12 weeks | 
| Efficacy in Modifying Health-related Quality of Life Measured by SF-36 | Short Form (36) Health Survey. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability. | 12 weeks | 
| Myositis Disease (MD) Activity Scores | Myositis Disease Activity Scores. This is a combined tool that captures the physician's assessment of disease activity of various organ systems via the MYOSITIS INTENTION TO TREAT ACTIVITY INDEX (MITAX) and via the MYOSITIS DISEASE ACTIVITY ASSESSMENT VISUAL ANALOGUE SCALES (MYOACT) It rates the physician's overall assessment of the ongoing current disease activity for various systems by drawing a vertical mark on the 10-cm line for each system according to the following scale: left end of line = no evidence of disease activity, midpoint of line = moderate disease activity, and right end of line = extreme or maximum disease activity. | Week 12 | 
| Physician Global Activity Assessment | Physician's overall assessment on a single 0-10 cm scale, where the higher score indicates higher disease activity. | Baseline, Week 12 | 
| Patient Global Activity Assessment | Patient's overall assessment on a single 0-10 cm scale, where the higher score indicates higher disease activity. | Baseline, Week 12 | 
| Manual Muscle Testing (MMT) - 8 Score | Manual Muscle Testing - 8 (MMT-8): Assessment of designated muscles manually by scoring each muscle from 0 to 10 where 0 is no strength and 10 is maximum strength. MMT- 8 includes 7 bilateral muscles (potential score 0-70 x 2) and one unilateral (axial) muscle (0-10 x1) so the total score ranges from 0 to 150 (maximum) where higher score indicates more strength. | Baseline, Week 12 | 
| Health Assessment Questionnaire | Health Assessment Questionnaire (HAQ): This questionnaire is a patient reported outcome (PRO) which is self-administered by the patient. It is used to assess disability and comprises various categories related to usual daily activities. The patients report the amount of difficulty they have in performing some of these activities. Each question asks on a scale ranging from 0 to 3 if the categories can be performed without any difficulty (scale 0) up to cannot be done at all (scale 3). The total score is derived from these sub-scores and ranges from 0 to 3 where higher HAQ indicates more disability. | Baseline, Week 12 | 
| Serum Levels of Muscle Enzymes |  | Baseline, Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inflammatory muscle disease, Muscle weakness, Myositis, inflammatory myopathy, inclusion body myositis, skin rash, autoimmune, difficulty swallowing, dysphagia