Safety and Efficacy of BAF312 in Dermatomyositis

Phase 2

Terminated

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
BAF312 0.5mg	BAF312	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.
Placebo	Placebo	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.
BAF312 2mg	BAF312	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.
BAF312 10 mg	BAF312	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Manual Muscle Testing - 24 Muscles (MMT-24) Score	Baseline, 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Peripheral Blood Lymphocyte Counts	baseline, 6 months	Absolute lymphocyte counts
Change From Baseline in Manual Muscle Testing - 24 Muscles (MMT-24) Score	baseline, 3 months	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.
Change From Baseline in 6 Minutes Walking Distance (6-MWD) Test	baseline, 6 months
BAF312 Plasma Concentration	6 months