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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

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ClinicalTrials.gov Identifier: NCT02971683
Recruitment Status : Terminated (Inability to meet protocol objectives)
First Posted : November 23, 2016
Results First Posted : September 17, 2021
Last Update Posted : August 8, 2022
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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

Condition or disease Intervention/treatment Phase
Polymyositis Dermatomyositis Autoimmune Necrotizing Myopathy Overlap Myositis Juvenile Myositis Above the Age of 18 Drug: Abatacept subcutaneous Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 149 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 4, 2017
Actual Primary Completion Date : July 27, 2020
Actual Study Completion Date : July 5, 2022


Arm Intervention/treatment
Active Comparator: Abatacept subcutaneous + Standard Treatment
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.
Drug: Abatacept subcutaneous
Specified dose of Abatacept subcutaneous on specified days

Placebo Comparator: Placebo of Abatacept subcutaneous + Standard Treatment
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.
Drug: Placebo
Placebo of Abatacept subcutaneous




Primary Outcome Measures :
  1. Number of Participants Achieving International Myositis Assessment and Clinical Studies Definition of Improvement (IMACS DOI) at Week 24 Without Rescue [ Time Frame: From first dose to 24 weeks after first dose. (Approximately 169 days) ]

    The number of participants who achieve IMACS DOI (International Myositis Assessment and Clinical Studies definition of improvement) without rescue medication at week 24.

    The IMACS DOI is: An improvement of >/= 20% from baseline in 3 IMACS core measures, no more than 2 IMACS core measure scores worsen by >/= 25% from baseline, and no more than 2 IMACS core measure scores worsen by >/= 25% from baseline.

    IMACS core measures are: Physician Global Assessment of Disease Activity (PGA), Patient (Subject) Global Assessment of Disease Activity (SGA), Manual Muscle Test (MMT-8), Health Assessment Questionnaire-Disability Index (HAQ-DI), Muscle Enzyme levels, Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity.



Secondary Outcome Measures :
  1. Mean Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 24. [ Time Frame: From first dose to 24 weeks after first dose. (Approximately 169 days) ]
    The adjusted mean change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI). HAQ-DI is a patient-reported outcome measuring disability by asking a total of 20 questions in eight categories of function: dressing, arising, eating, walking, hygiene, reach, grip, and activities. If an aid or device is used or if help is required from another individual, then the minimum score for that section is 2. The highest component score in each category determines the score for the category and scores are averaged to give the disability index. The HAQ scale ranges from 0 (no difficulties) to 3 (unable to do).

  2. Mean Change in Muscle Endurance Using the Myositis Function Index (FI-2) From Baseline to Week 24 [ Time Frame: From first dose to 24 weeks after first dose. (Approximately 169 days) ]

    The adjusted mean change from baseline in Myositis FI-2 scores is assessing muscle endurance impairment by testing specific muscle groups. The 3 Score average includes shoulder flexion, hip flexion, and head lift. Each muscle group is scored as the number of correctly performed repetitions with 60 maximal number of repetitions.

    The total score is based on hip flexion, shoulder flexion (R/L) and neck divided by 3 (range 0-60 repetitions).


  3. Mean Change in Myositis Disease Activity Assessment Tool (MDAAT) Assessment of Extra-muscular From Baseline to Week 24. [ Time Frame: From first dose to 24 weeks after first dose. (Approximately 169 days) ]

    The adjusted mean change from baseline in the Myositis Disease Activity Assessment Tool (MDAAT) assessment of extra-muscular uses a 100 mm Visual Analog Scale (VAS) scale. This VAS assesses the overall extra-muscular clinical features based upon: 1) The presence of clinical features or symptoms within the previous 4 weeks that are due to active disease. 2) The judgment that the feature is due to the myositis disease process. 3) The concept that disease activity is defined as a potentially reversible finding. 4) A clinical, functional, and laboratory assessments.

    The scoring is performed by the investigator and ranges from 0 (absent extra-muscular disease activity) to 100 (maximum extra-muscular disease activity).


  4. Myositis Response Criteria (MRC) Total Improvement Score From Baseline to Week 24. [ Time Frame: From first dose to 24 weeks after first dose. (Approximately 169 days) ]

    The Myositis Response Criteria (MRC) is a continuous total improvement score from baseline (range 0-100) based on the sum of the absolute percent change in the 6 core domains (weighted) used in the IMACS DOI (International Myositis Assessment and Clinical Studies definition of improvement)

    IMACS core measures are: Physician Global Assessment of Disease Activity (PGA), Patient (Subject) Global Assessment of Disease Activity (SGA), Manual Muscle Test (MMT-8), Health Assessment Questionnaire-Disability Index (HAQ-DI), Muscle Enzyme levels, Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity.

    The total improvement score ranges between 0 and 100 percent corresponds to the degree of improvement, with higher scores corresponding to a greater degree of improvement ( >/= 20 represents minimal improvement, a score of >/= 40 represents moderate improvement, and a score of >/= 60 represents major improvement).


  5. Number of Participants Experiencing Adverse Events (AE) in the Double-Blind Period [ Time Frame: From first dose up to approximately 56 days post last dose date in double-blind period or first dose in open-label period. ]
    The number of treated participants experiencing an adverse event. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in participants administered a study drug and that does not necessarily have a causal relationship with the treatment.

  6. Number of Participants Experiencing Serious Adverse Events (SAE) in the Double-Blind Period [ Time Frame: From first dose up to approximately 56 days post last dose date in double-blind period or first dose in open-label period. ]
    The number of treated participants experiencing a Serious Adverse Event (SAE). A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

  7. Number of Participants Experiencing Adverse Events (AE) of Special Interest in the Double-Blind Period [ Time Frame: From first dose up to approximately 56 days post last dose date in double-blind period or first dose in open-label period. ]
    The number of treated participants experiencing adverse events of special interest: infections, malignancies, autoimmune events, local injection site reactions, and systemic injection reactions.

  8. Number of Participants Experiencing Laboratory Test Abnormalities in the Double-Blind Period [ Time Frame: From first dose up to approximately 56 days post last dose date in double-blind period or first dose in open-label period. ]
    The number of participants experiencing laboratory test abnormalities. Laboratory analysis was performed on the following: hematology, liver and kidney function, electrolytes, other chemistry testing (glucose, protein, cardiac), and urine chemistry. Only tests with participants experiencing abnormalities were reported.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02971683


Locations
Show Show 76 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] February 1, 2019
Statistical Analysis Plan  [PDF] December 15, 2020

Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02971683    
Other Study ID Numbers: IM101-611
2016-002269-77 ( EudraCT Number )
First Posted: November 23, 2016    Key Record Dates
Results First Posted: September 17, 2021
Last Update Posted: August 8, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Diseases
Dermatomyositis
Myositis
Polymyositis
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Connective Tissue Diseases
Skin Diseases
Abatacept
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents