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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 3

Conditions: Dermatomyositis; Polymyositis; Overlap Myositis; Juvenile Myositis Above the Age of 18; Autoimmune Necrotizing Myopathy

Treatments: Drug: Placebo; Drug: Abatacept subcutaneous

Study type: Interventional

Funder types: Industry

Identifiers

NCT02971683

IM101-611

2016-002269-77 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 149 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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149 participants in 2 patient groups, including a placebo group

Abatacept subcutaneous + Standard Treatment

Active Comparator group

Description:

Abatacept subcutaneous weekly in addition to the subject's current standard treatment for 24 weeks followed by a 28 week open-label period of abatacept treatment plus the subject's current standard treatment.

Treatment:

Drug: Abatacept subcutaneous

Placebo of Abatacept subcutaneous + Standard Treatment

Placebo Comparator group

Description:

Placebo of Abatacept subcutaneous weekly in addition to the subject's current standard treatment for 24 weeks followed by a 28 week open-label period of abatacept treatment plus the subject's current standard treatment.

Treatment:

Drug: Placebo