Polymyositis (PM)

The purpose of the study is to determine the efficacy, safety, tolerability and the PK profile of 2 mg BAF312 administered orally in clinically active PM patients defined by decreased muscle strength and elevated levels of serum CK. The patient population will comprise PM patients who have shown inadequate response to corticosteroids and/or DMARDs. Recently obtained data from study CBAF312A2202 in an active PM/DM (polymyositis/ dermatomyositis) patient population suggested a trend for efficacy in both patient subpopulations.

BAF312

Siponimab

tablet

0, 0.25, 1

Primary Objective
To assess the preliminary clinical efficacy of 2mg BAF312 once daily in patients with PM using manual
muscle testing (MMT) and serum creatine kinase (CK)
Secondary Objective
To assess the safety, tolerability and pharmacokinetics of BAF312 in patients with PM

• Male and female patients between 18 - 75 (inclusive) years of age who have been defined as
"definite" or “probable” based on the criteria of Bohan and Peter (Bohan and Peter 1975) for
polymyositis
• Patients must have active disease as defined by CK levels and persisting muscle weakness
• Patients must have received, but inadequately responding to, standard therapies as defined by
corticosteroid alone or in combination with disease modifying antirheumatic drugs
• Patients must be on a stable dose of corticosteroid for at least 2 weeks prior to Baseline and
should not have received a medium or high dose corticosteroid therapy in the last 8 weeks prior to
study entry
• Patients currently treated with oral or subcutaneous methotrexate must have been on a stable
dose of no more than 25 mg per week for at least 6 weeks prior to Baseline

• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
• Polymyositis patients having:
• overlap polymyositis if the muscle symptoms are attributable to other causes (e.g. arthritis,
organ damage, scleroderma or steroid induced myopathy);
• preexisting severe cardiac or pulmonary involvement;
• late-stage polymyositis attributable to muscle damage.
• Patients with other types of myositis or myopathies including: dermatomyositis, paraneoplastic
polymyositis, inclusion body myositis, necrotizing myopathy, any myopathy due to conditions other
than PM
• Patients who have been treated with immunoglobulins such as intravenous immunoglobulin (ivIg)
within 3 months prior to randomization, monoclonal antibodies or cyclophosphamide within
6 months prior to randomization. For patients treated with rituximab in the past 12 months,
peripheral B cell count should be in the normal range to be eligible to the study
• Patients with concurrent or history of macular edema or any significant eye disease that increases
the risk of macular edema (e.g. diabetic retinopathy or retinal vein occlusion)
• Pre-existing cardiovascular, pulmonary, hepatic conditions as listed in Section 4.2.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin),
treated or untreated, within the past 5 years, regardless of whether there is evidence of local
recurrence or metastases
• Uncontrolled diabetes mellitus or diabetes complicated with organ involvement such as diabetic
nephropathy or retinopathy
• Acute or chronic infectious diseases, active systemic bacterial, viral (e.g. AIDS, Hepatitis B,
Hepatitis C) or fungal infections
• Pregnant or nursing (lactating) women and women of child-bearing potential