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Belimumab in Idiopathic Inflammatory Myositis (BIM)

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ClinicalTrials.gov Identifier: NCT02347891
Recruitment Status : Recruiting
First Posted : January 28, 2015
Last Update Posted : August 23, 2018
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Galina Marder, MD, Northwell Health

Tracking Information
First Submitted Date  ICMJE January 22, 2015
First Posted Date  ICMJE January 28, 2015
Last Update Posted Date August 23, 2018
Study Start Date  ICMJE January 2015
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2015)
Response Rate [ Time Frame: 40 weeks ]
percentage of patients meeting definition of improvement (DOI) in both groups
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02347891 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2015)
Incidence of Flares [ Time Frame: 40 and 64 weeks ]
The flare rates in patients in belimumab arm compared to the flare rates of patients in the placebo arm
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Belimumab in Idiopathic Inflammatory Myositis
Official Title  ICMJE Belimumab for Maintenance Therapy in Idiopathic Inflammatory Myositis
Brief Summary The goal of the trial is to evaluate the efficacy and safety of belimumab as a maintenance therapy in adults with refractory Idiopathic inflammatory myositis (IIM) as compared with standard of care. This is a multicentre double-blind, placebo-controlled trial.
Detailed Description Adults with refractory IIM will be enrolled. IIM is defined as Dermatomyositis (DM) or Polymyositis (PM), meeting the Bohan & Peter (1975) diagnostic criteria for definite or probable DM or PM. Refractory IIM is defined as chronic active IIM with a history of inadequate response or intolerance to three months of glucocorticoids and/or at least a history of inadequate response or intolerance to three months of one other immunosuppressive agent (IS) (azathioprine, methotrexate, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine, cyclophosphamide, Rituximab or intravenous gamma globulin [IVIG]).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Myositis
Intervention  ICMJE
  • Drug: Belimumab
    Randomized phase: Week 0 - Week 36
    Other Name: Benlysta
  • Drug: Placebo
    Randomized phase: Week 0 - Week 36
    Other Name: Saline IV bag
Study Arms  ICMJE
  • Experimental: Belimumab + Standard of Care

    Patients in this arm will be given belimumab with a background of standard of care therapy during the randomized controlled treatment period.

    Patients in this arm will continue to receive belimumab during the open label phase of the study (week 40 - week 64)

    Intervention: Drug: Belimumab
  • Active Comparator: Placebo + Standard of Care

    Patients in this arm will be given a placebo with a background of standard of care therapy during the randomized controlled treatment period.

    Patients in this arm will receive belimumab during the open label phase of the study (week 40 - week 64).

    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 22, 2015)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Subjects enrolled in the study must meet the following inclusion criteria:

  1. Adults >18 years of age
  2. Have a diagnosis of:

    1. definite or probable dermatomyositis (DM) or
    2. Definite or probable diagnosis of polymyositis (PM) with presence of one of myositis specific antibodies. In the absence of myositis specific auto-antibodies, the diagnosis of PM will require review of the muscle biopsy and adjudication by the predetermined committee of experts.
  3. Presence of positive autoantibody (ANA >1:80 or RNP or SSA/SSB or any of the myositis specific autoantibody: antisynthetase autoantibodies (anti-Jo-1, PL-7, PL-12, EJ, OJ, KS), anti-SRP, anti-Mi-2, anti-p140).
  4. Have refractory IIM as defined by inadequate response or intolerance to at least 3 months of glucocorticoids and/or at least one other immunosuppressive agent, such as azathioprine, methotrexate, IVIG, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine cyclophosphamide, and Rituximab.
  5. Have active IIM at screening. This requires at least 3 criteria from the CSM
  6. Dermatomyositis patients that do not meet the MMT criteria, must have:

    1. a cutaneous VAS score of >3 cm on a 10 cm VAS scale (MDAAT) will be required:
    2. elevation of at least one muscle enzyme (creatine kinase [CK]; aldolase; lactate dehydrogenase [LDH]; alanine aminotransferase [ALT]; or aspartate aminotransferase [AST]) to a minimum level of 1.3 times the upper limit of normal,
    3. and 1 additional core set measure
  7. For patients with ≥ 7 years of IIM, muscle biopsy or muscle MRI within 4 months prior to enrollment will be required to document active myositis to avoid enrolling patients with significant index of damage/ muscle atrophy. This is not applicable to DM patients with a cutaneous VAS score of >3 cm on a 10 cm VAS scale (MDAAT).
  8. Have a stable background glucocorticoid therapy for at least 2 weeks prior to screening (Prednisone (or equivalent) dose < 15 mg daily)
  9. Have a stable immunosuppressive therapy (IS) (azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine for > 2 months prior to screening. Patients on intravenous gamma globulin (IVIG) have to be on a stable dose and frequency regimen for ≥ 3 months.
  10. Have the ability to understand the requirements of the study and provide written informed consent (including consent for the use and disclosure of research-related health information) and comply with the study protocol procedures (including required study visits)
  11. Female subjects of childbearing potential must have a negative urine pregnancy test at screening and agree to 1 of the following:

    1. Complete abstinence from intercourse from 2 weeks prior to administration of the 1st dose of study agent until 16 weeks after the last dose of study agent (Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception); or
    2. Consistent and correct use of 2 of acceptable methods of birth control for 1 month prior to the start of the study agent, during the study, and 16 weeks after the last dose of study agent

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

  1. Have severe muscle damage as defined by a Muscle Damage Index (MDI) > 5.0 cm using a visual analogue scale (VAS) 10.0 cm in length or evidence of severe muscle atrophy on muscle MRI.
  2. History of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell).
  3. Have a history of a primary immunodeficiency
  4. Have a significant IgG deficiency (IgG level < 400 mg/dl) Have an IgA deficiency (IgA level < 10 mg/dL)
  5. Discontinuation IS agent < 3 months prior to Screening. Including: azathioprine, methotrexate, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine, or intravenous gamma globulin [IVIG]
  6. Have received Rituximab within 365 days prior to Screening.
  7. Have received cyclophosphamide within 180 days prior to Screening
  8. Have received treatment with:

    1. Initiated IVIG 3 months prior to Screening
    2. Pulse steroids 2 months prior to Screening
  9. Have received treatment with Belimumab at any time prior to Screening
  10. Have received a biologic investigational agent within 365 days prior to Screening.
  11. Have received a non-biologic investigational agent within 30 days or 5 half-lives of the agent (whichever is longer) prior to Screening.
  12. Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.
  13. Infection history:

    1. Currently on any suppressive therapy for a chronic infection (such as tuberculosis - including latent tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria).

      NOTE: Testing for latent TB is a standard of care for patients on immunosuppressive therapy and results will be obtained from their medical record. If no TB history is found for these patients, a Quantiferon Gold or PPD test will be performed prior to Day 0 as part of standard of care.

    2. Hospitalization for treatment of infection within 60 days of Day 0.
    3. Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of Day 0.
  14. Have a historically positive HIV test or test positive at screening for HIV.
  15. Have a history of autoimmune hepatitis
  16. Hepatitis status will be obtained from patients' medical records. If unavailable, testing will be done as part of standard of care. Patients are excluded if there is evidence of infection with:

    a. Hepatitis B: i. Positive hepatitis B surface antigen (HBsAg) or positive hepatitis B core antibody (HBcAb) or b. Hepatitis C: i. Positive hepatitis C antibody with confirmatory hepatitis C viral load by PCR.

  17. Clinically significant elevation of GGT (>1.5xULN), bilirubin (>1.25xULN, direct 35%), or INR (>1.2, excluding patients on anti-coagulant therapies) or other clinically significant abnormal laboratory value in the opinion of the investigator.
  18. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0.
  19. Have evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, pose a significant suicide risk.
  20. Have any concurrent significant medical or psychiatric illness that the investigator considers would make the candidate unsuitable for the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Preeya Nandkumar 5167082556 pnandkumar@nshs.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02347891
Other Study ID Numbers  ICMJE 14-621
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Galina Marder, MD, Northwell Health
Study Sponsor  ICMJE Northwell Health
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Principal Investigator: Galina Marder, MD NorthShore-LIJ Health System
PRS Account Northwell Health
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP