Trial to Evaluate the Efficacy and Safety of Abatacept in Combination With Standard Therapy Compared to Standard Therapy Alone in Improving Disease Activity in Adults With Active Idiopathic Inflammatory Myopathy
Condition: Polymyositis; Dermatomyositis; Autoimmune Necrotizing Myopathy; Overlap Myositis; Juvenile Myositis Above the Age of 18
MeSH terms: Muscular Diseases; Dermatomyositis; Myositis; Polymyositis
Intervention: Abatacept subcutaneous; Placebo
Intervention description: Specified dose of Abatacept subcutaneous on specified days; Placebo of Abatacept subcutaneous
Intervention MeSH terms: Abatacept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 149.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Trial to Evaluate the Efficacy and Safety of Abatacept subcutaneous (SC) in Combination With
      Standard Therapy Compared to Standard Therapy Alone in Improving Disease Activity in Adults
      With Active Idiopathic Inflammatory Myopathy
    

Eligibility criteria:

        Inclusion Criteria:

        -Diagnosis of IIM based on the Bohan and Peter classification criteria: i) Subjects with
        dermatomyositis (DM) must also have a confirmed myositis-associated rash (Gottron's papules
        or a heliotrope rash preferably confirmed by skin biopsy) and 2 or more of the remaining 4
        criteria.

        ii) Subjects with a diagnosis of IIM other than DM include PM, autoimmune necrotizing
        myopathy, myositis in association with another connective tissue disease (overlap myositis)
        and juvenile myositis subjects above the age of 18. These subjects must have a prior muscle
        biopsy diagnostic for IIM or a positive test for at least one myositis-specific
        autoantibody (anti-aminoacyl-tRNA synthetases (Jo-1, PL-7, PL-12, EJ, OJ, KS, Zo, YRS),
        anti-Mi-2, anti-SRP, anti-TIF1-g, anti-NXP-2, anti-MDA5, anti-SAE, anti-HMGCR). For
        subjects with overlap myositis, the myositis must be the principal clinically active
        manifestation of their disease. Where applicable, documentation of prior skin biopsy,
        muscle biopsy, and autoantibody results must be obtained and retained by the site.

          -  Demonstrable muscle weakness measured by the MMT-8 of ≤ 135 units and any 3 of the
             following: i) MMT-8 ≤ 125 units; ii) Physician's global assessment (PGA) visual analog
             scale (VAS) ≥2 cm; iii) Subject's global assessment (SGA) VAS ≥2 cm; iv) HAQ-DI ≥ 0.5;
             v) One or more muscle enzyme (CK, aldolase, LDH, AST, ALT) ³ 1.3 times upper limit of
             normal (ULN); vi) MDAAT Extramuscular Global Activity VAS ≥2 cm

          -  Demonstration of currently active IIM will be determined by an adjudication committee
             unless the subject has any one of the following: i) an active myositis-associated rash
             (Gottron's papules or heliotrope rash), or ii) a recent (within 3 months prior to
             signing informed consent) biopsy, magnetic resonance imaging (MRI), or electromyogram
             (EMG) demonstrating active disease, or iii) an elevated CK > 5 times the upper limit
             of normal

          -  Active disease despite prior treatment with corticosteroids, immunosuppressants, or
             biologics as determined by the investigator

          -  The subject must be on background standard treatment for IIM. The standard treatments
             that are allowed as background treatment for IIM includes: i) Corticosteroids alone,
             or ii) One of the following immunosuppressants: methotrexate, azathioprine,
             mycophenolate mofetil, tacrolimus, or cyclosporine (combinations of these treatments
             are not allowed), or iii) A combination of corticosteroids and one of the above
             immunosuppressants. The subject must have been on the same medication(s) for IIM for
             12 weeks prior to randomization and the dose must have been stable for 4 weeks prior
             to randomization. If using azathioprine, the subject must have been on azathioprine
             for at least 24 weeks with a stable dose for at least 12 weeks prior to randomization.

        Exclusion Criteria:

          -  Subjects with Inclusion Body Myositis (IBM), or myositis other than IIM, eg,
             drug-induced myositis and PM associated with HIV

          -  Subjects treated with penicillamine or zidovudine in the past 3 months

          -  Subjects treated with rituximab in the 6 months prior to randomization (there must be
             laboratory results indicating the presence of circulating B cells [CD19+]). Any other
             biologic treatment in the past 3 months or immune globulin (intravenous [IVIG] or
             subcutaneous [SCIG]) in the past 3 months prior to randomization

          -  Subjects with uncontrolled or rapidly progressive interstitial lung disease

          -  Subjects with severe muscle damage (Myositis Damage Index > 7/10), permanent weakness
             due to a non-IIM cause, or myositis with cardiac involvement

          -  Cancer-associated myositis (myositis diagnosed within 2 years of a diagnosis of cancer

          -  Subjects who are known to be positive for the anti-TIF-1 (p155/140) autoantibody prior
             to randomization who were diagnosed with IIM < 1 year prior to randomization.

          -  Subjects at risk for tuberculosis

          -  Subjects with recent acute infection requiring antibiotics

          -  Subjects with history of chronic or recurrent bacterial, viral or systemic fungal
             infections

          -  Subjects who have a present malignancy or have had a previous malignancy within the
             last 5 years prior to screening (except for a documented history of cured
             non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ).

        Other protocol-defined inclusion/exclusion criteria apply