Efficacy and Tolerability of BAF312 in Patients With Polymyositis

Study Overview
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Brief Summary
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This study assessed the efficacy, safety and tolerability of BAF312 administered orally in patients with clinically active polymyositis and also in patients with polymyositis who had shown inadequate response to corticosteroids and or DMARDs (disease modifying antirheumatic drugs).

Detailed Description
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This study was stopped prematurely due to overall slow recruitment and no evidence for efficacy in a parallel study in dermatomyositis with an assumed similar pathophysiology. With very small sample sizes per group the overall results for this study including primary and all other efficacy and PD data are inconclusive

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

Conditions
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Polymyositis

Intervention / Treatment
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* Drug: Placebo
* Drug: BAF312


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: definite or probable for polymyositis at least three months before Baseline active disease as defined by elevated CK levels, or other enzymes, or MRI/biopsy if enzymes are normal, and persisting muscle weakness stable dose of corticosteroid for at least 2 weeks prior to Baseline and should not have received a medium or high dose in the last 8 weeks prior to study entry. patients treated with methotrexate must have been on a stable dose for at least 6 weeks prior to Baseline. Exclusion Criteria: Patients with overlap polymyositis, late-stage polymyositis, or other types of myositis. Preexisting severe cardiac or pulmonary involvement, malignancy of any organ system or significant eye diseases. Uncontrolled diabetes mellitus or diabetes complicated with organ involvement. Pregnant or nursing (lactating) women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>5 placebo tablets daily during non-titration phase | Drug: Placebo<br>* Matching placebo tablet for oral administration<br>|
| Experimental: BAF312 2mg<br>1 tablet of BAF312 2 mg + 4 tablets of Placebo daily during non-titration phase | Drug: BAF312<br>* BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration<br>|
| Experimental: BAF312 10 mg<br>5 tablets of BAF312 2 mg daily during non-titration phase | Drug: BAF312<br>* BAF312 in 4 dosage strengths in tablet form: 0.25 mg, 0.5 mg, 1 mg, 2 mg for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) for Combined Efficacy Endpoint: Manual Muscle Testing in 24 Muscles (MMT24) | Manual Muscle Testing Scoring Sheet: Neck flexors, neck extensors and other designated muscles bilaterally (Biceps brachii, Deltoid middle, Quadriceps, Gluteus maximus, Gluteus medius, Trapezius, Iliopsoas, Hamstrings, Wrist extensors, Wrist Flexors, Ankle plantar flexors and Ankle dorsiflexors) were tested on a 0-10 scale by the Investigator. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The scores range was 0 to 260. Higher scores indicate better outcome. | Baseline, at 12 weeks | 
| Percent Change From Baseline at Week 12 for BAF312 2 mg, 10 mg or Placebo (Once Daily) Serum Creatine Kinase (CK) Levels | Serum creatine kinase (CK) were analyzed as part of the blood chemistry panel. Posterior credibility interval from Bayesian analysis displayed as confidence interval. The variable CK was log-transformed for statistical analysis and after estimation was converted to percent change from baseline divided by the mean baseline | Baseline, at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-minute Walking Distance (6MWD) at Week 12 | This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted | Baseline, 12 weeks | 
| Six-minute Walking Distance (6MWD) at Week 24 | This test assessed the distance a patient could walk in 6 minutes (Rutkove et al 2002). If the patient was not able to walk for 6 minutes then a 2 minute walking test was conducted | Baseline, 24 weeks | 
| BAF312 Trough Plasma Concentrations (PK Set) | All blood samples were taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. For each sample, approximately 2 mL of blood was drawn. BAF312 was determined in ethylenediaminetetraacetic acid (EDTA) plasma using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method for the quantification. The anticipated lower limit of quantification (LLOQ) was 0.02 ng/mL using 0.1 mL of plasma | -7 Baseline, day 28, 56, 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PM, Polymyositis, Myositis, chronic muscle inflammation, inflammatory myopathy, inclusion body myositis