Clinical trial NCT02971683: 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
Official title: A Phase 3, Randomized, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Abatacept SC With Standard Treatment Compared to Standard Treatment Alone in Improving Disease Activity in Adults With Active Idiopathic Inflammatory Myopathy (IIM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polymyositis
Dermatomyositis
Autoimmune Necrotizing Myopathy
Overlap Myositis
Juvenile Myositis Above the Age of 18
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2016-11-23
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Number of Participants Achieving International Myositis Assessment and Clinical Studies Definition of Improvement (IMACS DOI) at Week 24 Without Rescue
timeFrame: From first dose to 24 weeks after first dose. (Approximately 169 days)
Secondary outcomes:
measure: Mean Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 24
timeFrame: From first dose to 24 weeks after first dose. (Approximately 169 days)
measure: Mean Change in Muscle Endurance Using the Myositis Function Index (FI-2) From Baseline to Week 24
timeFrame: From first dose to 24 weeks after first dose. (Approximately 169 days)
measure: Mean Change in Myositis Disease Activity Assessment Tool (MDAAT) Assessment of Extra-muscular From Baseline to Week 24
timeFrame: From first dose to 24 weeks after first dose. (Approximately 169 days)
measure: Myositis Response Criteria (MRC) Total Improvement Score From Baseline to Week 24
timeFrame: From first dose to 24 weeks after first dose. (Approximately 169 days)
measure: Number of Participants Experiencing Adverse Events (AE) in the Double-Blind Period
timeFrame: From first dose up to approximately 56 days post last dose date in double-blind period or first dose in open-label period. (Up to approximately 274 days)
measure: Number of Participants Experiencing Serious Adverse Events (SAE) in the Double-Blind Period
timeFrame: From first dose up to approximately 56 days post last dose date in double-blind period or first dose in open-label period. (Up to approximately 274 days)
measure: Number of Participants Experiencing Adverse Events (AE) of Special Interest in the Double-Blind Period
timeFrame: From first dose up to approximately 56 days post last dose date in double-blind period or first dose in open-label period. (Up to approximately 274 days)
measure: Number of Participants Experiencing Laboratory Test Abnormalities in the Double-Blind Period
timeFrame: From first dose up to approximately 56 days post last dose date in double-blind period or first dose in open-label period. (Up to approximately 274 days)
measure: Number of Participants Experiencing Adverse Events (AE) in the Cumulative Abatacept Period
timeFrame: From first dose up to approximately 56 days post last dose (up to approximately 54 months)
measure: Number of Participants Experiencing Serious Adverse Events (SAE) in the Cumulative Abatacept Period
timeFrame: From first dose up to approximately 56 days post last dose (up to approximately 54 months)
measure: Number of Participants Experiencing Adverse Events (AE) of Special Interest in the Cumulative Abatacept Period
timeFrame: From first dose up to approximately 56 days post last dose (up to approximately 54 months)
measure: Number of Participants Experiencing Laboratory Test Abnormalities in the Open-Label Period
timeFrame: From first dose in open label period to first dose date in the subsequent period or up to 56 days post last dose (up to approximately 666 days)
measure: Number of Participants Experiencing Laboratory Test Abnormalities in the Long-Term Open Label Period
timeFrame: From first dose in the Long-Term Open Label Period up to 56 days post last dose in the Long-Term Open Label Period (up to approximately 958 days)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Local Institution - 0015
state: Arizona
city: Beverly Hills
country: United States
facility: Local Institution - 0075
state: California
city: Orange
country: United States
facility: Local Institution - 0012
state: California
city: Washington
country: United States
facility: Local Institution - 0057
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Local Institution - 0018
state: Florida
city: Miami
country: United States
facility: Local Institution - 0013
state: Florida
city: Kansas City
country: United States
facility: Local Institution - 0006
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University -Johns Hopkins Bayview Medical Center
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0058
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0089
state: Michigan
city: Eagan
country: United States
facility: Local Institution - 0002
state: Minnesota
city: Omaha
country: United States
facility: Local Institution - 0011
state: Nebraska
city: Lebanon
country: United States
facility: Local Institution - 0004
state: New Hampshire
city: New York
country: United States
facility: Local Institution - 0097
state: New York
city: Wilmington
country: United States
facility: Local Institution - 0010
state: North Carolina
city: Columbus
country: United States
facility: Local Institution - 0056
state: Ohio
city: Middleburg Heights
country: United States
facility: Local Institution - 0094
state: Ohio
city: Norman
country: United States
facility: Local Institution - 0059
state: Oklahoma
city: Bethlehem
country: United States
facility: Local Institution - 0055
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution - 0014
state: Pennsylvania
city: Orangeburg
country: United States
facility: Local Institution - 0005
state: South Carolina
city: Jackson
country: United States
facility: Local Institution - 0017
state: Tennessee
city: Austin
country: United States
facility: Local Institution - 0096
state: Texas
city: Houston
country: United States
facility: Local Institution - 0016
state: Texas
city: Seattle
country: United States
facility: Local Institution - 0095
state: Washington
city: Camperdown
country: Australia
facility: Local Institution - 0051
state: New South Wales
city: St Leonards
country: Australia
facility: Local Institution - 0053
state: New South Wales
city: Auchenflower
country: Australia
facility: Local Institution - 0035
state: Queensland
city: Murdoch
country: Australia
facility: Local Institution - 0036
state: Western Australia
city: Salvador
country: Brazil
facility: Local Institution - 0073
state: Bahia
city: Vitoria
country: Brazil
facility: Local Institution - 0070
state: Espirito Santo
city: Juiz de Fora
country: Brazil
facility: Local Institution - 0069
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Local Institution - 0072
state: RIO Grande DO SUL
city: Bairro Jardim
country: Brazil
facility: Local Institution - 0074
state: SAO Paulo
city: Rio Grande Do Sul
country: Brazil
facility: Local Institution - 0067
city: Sao Paulo
country: Brazil
facility: Local Institution - 0071
city: Praha 2
country: Czechia
facility: Local Institution - 0029
city: Brest
country: France
facility: Local Institution - 0100
city: Clermont Ferrand Cedex 1
country: France
facility: Local Institution - 0045
city: Lille Cedex
country: France
facility: Local Institution - 0043
city: Paris
country: France
facility: Local Institution - 0042
city: Strasbourg
country: France
facility: Local Institution - 0044
city: Berlin
country: Germany
facility: Local Institution - 0027
city: Halle (saale)
country: Germany
facility: Local Institution - 0054
city: Hamburg
country: Germany
facility: Local Institution - 0028
city: Munchen
country: Germany
facility: Local Institution - 0030
city: Pavia
country: Italy
facility: Local Institution - 0023
state: Lombardia
city: Ferrara
country: Italy
facility: Local Institution - 0031
city: Firenze
country: Italy
facility: Local Institution - 0024
city: Padova
country: Italy
facility: Local Institution - 0020
city: Pisa
country: Italy
facility: Local Institution - 0025
city: Kitakyushu
country: Japan
facility: Local Institution - 0091
state: Fukuoka
city: Sapporo-City
country: Japan
facility: Local Institution - 0090
state: Hokkaido
city: Sapporo
country: Japan
facility: Local Institution - 0078
state: Hokkaido
city: Tsukuba
country: Japan
facility: Local Institution - 0082
state: Ibaraki
city: Kawasaki-shi
country: Japan
facility: Local Institution - 0083
state: Kanagawa
city: Kumamoto-city
country: Japan
facility: Local Institution - 0084
state: Kumamoto
city: Nagasaki-shi
country: Japan
facility: Local Institution - 0088
state: Nagasaki
city: Sasebo city
country: Japan
facility: Local Institution
state: Nagasaki
city: Iruma-gun
country: Japan
facility: Local Institution - 0077
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0086
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0079
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0081
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Local Institution - 0092
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Local Institution - 0093
state: Tokyo
city: Ube-shi
country: Japan
facility: Local Institution - 0087
state: Yamaguchi
city: Miyagi
country: Japan
facility: Local Institution - 0076
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0066
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0065
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0064
city: Mexico City
country: Mexico
facility: Local Institution - 0049
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution - 0046
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution - 0048
state: Jalisco
city: San Luis Potosi
country: Mexico
facility: Local Institution - 0047
city: San Luis Potosi
country: Mexico
facility: Local Institution - 0052
city: Lund
country: Sweden
facility: Local Institution - 0040
city: Orebro
country: Sweden
facility: Local Institution - 0041
city: Stockholm
country: Sweden
facility: Local Institution - 0037
city: Vasteras
country: Sweden
facility: Local Institution - 0038
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: