Safety and Efficacy of BAF312 in Dermatomyositis

Study Overview
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Brief Summary
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This study investigated the dose response relationship for the efficacy and safety of BAF312 compared to placebo in active DM patients over a treatment period of 6+6 months and to determine the minimum dose required for a maximal clinical effect. The study was composed of 2 periods: a double-blind period 1 with BAF312 administered at different daily doses (0.5, 2, 10 mg and placebo) and a fixed-dose Period 2 in which BAF312 was administered at the dose of 2 mg daily .

Detailed Description
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The study was prematurely terminated based on the results of an interim analysis where BAF312 did not demonstrate superior efficacy over placebo and a dose-response relationship was not observed. There were no safety concerns. Approximately 56 participants were planned to be randomized. A total of 17 participants were enrolled and randomized by the time the study was terminated.

Official Title
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A Double Blind, Randomized, Placebo-controlled Study to Evaluate, Safety, Tolerability, Efficacy and Preliminary Dose-response of BAF312 in Patients With Active Dermatomyositis (DM)

Conditions
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Active Dermatomyositis

Intervention / Treatment
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* Drug: BAF312
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Patients who have been defined as definite or probable based on the criteria of Bohan and Peter (Bohan and Peter 1975) for dermatomyositis at least 3 months before screening Patients must have active disease as defined by muscle weakness Patients may be on a stable dose of corticosteroid (up/equal to 20 mg once daily prednisone equivalent) Patients currently treated with oral or subcutaneous MTX must have been a stable dose of no more/equal to than 25 mg per week Patients currently treated with Azathioprine must have been a stable maintenance dose of no more/equal to 3 mg/kg/day Negative cancer screening conducted in the 12 months prior to screening visit Key Exclusion Criteria Dermatomyositis patients having overlap myositis or any other type of myositis including paraneoplastic myositis, drug-induced myopathy, necrotizing myositis Preexisting severe cardiac or pulmonary conditions, 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAF312 0.5mg<br>During period 1, participants were uptitrated daily from BAF312 0.25 mg to 0.5 mg over a 10 day period. After, participants continued on 0.5 mg daily for up to 24 weeks. During period 2, participants were uptitrated daily from BAF312 0.25 mg to 2.0 mg over a 10 day period. After, participants continued on 2.0 mg daily for up to 24 weeks. | Drug: BAF312<br>* BAF312 was provided as film-coated tablets in strengths of 0.25, 0,5, 1 and 2 mg for oral administration.<br>* Other names: Siponimod;|
| Experimental: BAF312 2mg<br>During period 1, participants were uptitrated daily from BAF312 0.25 mg to 2.0 mg over a 10 day period. After, participants continued on 2.0 mg daily for up to 24 weeks. During period 2, participants were uptitrated daily from BAF312 0.25 mg to 2.0 mg over a 10 day period. After, participants continued on 2.0 mg daily for up to 24 weeks. | Drug: BAF312<br>* BAF312 was provided as film-coated tablets in strengths of 0.25, 0,5, 1 and 2 mg for oral administration.<br>* Other names: Siponimod;|
| Experimental: BAF312 10 mg<br>During period 1, participants were uptitrated daily from BAF312 0.25 mg to 10.0 mg over a 10 day period. After, participants continued on 10.0 mg daily for up to 24 weeks. During period 2, participants were uptitrated daily from BAF312 0.25 mg to 2.0 mg over a 10 day period. After, participants continued on 2.0 mg daily for up to 24 weeks. | Drug: BAF312<br>* BAF312 was provided as film-coated tablets in strengths of 0.25, 0,5, 1 and 2 mg for oral administration.<br>* Other names: Siponimod;|
| Placebo Comparator: Placebo<br>During period 1, participants received matching placebo daily for up to 24 weeks. During period 2, participants were uptitrated daily from BAF312 0.25 mg to 2.0 mg over a 10 day period. After, participants continued on 2.0 mg daily for up to 24 weeks. | Drug: Placebo<br>* Matching placebo to BAF312 as tablets 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 in Manual Muscle Testing - 24 Muscles (MMT-24) Score | Each muscles tested was evaluated on a 0 - 10 scale where 0 indicated the weakest muscle score and 10 indicated the strongest muscle score. The total MMT24 score ranged from 0 - 240, where an increasing trend in the values indicates improvement. A positive change from baseline indicates improvement. | Baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BAF312 Plasma Concentration |  | 6 months | 
| Peripheral Blood Lymphocyte Counts | Absolute lymphocyte counts | baseline, 6 months | 
| Change From Baseline in Manual Muscle Testing - 24 Muscles (MMT-24) Score | Each muscles tested was evaluated on a 0-10 scale where 0 indicated the weakest muscle score and 10 indicated the strongest muscle score. the total MMT24 score ranged from 0-240, where an increasing trend in the values indicates improvement. A positive change from baseline indicates improvement. | baseline, 3 months | 
| Change From Baseline in 6 Minutes Walking Distance (6-MWD) Test |  | baseline, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dermatomyositis