Abatacept Treatment in Polymyositis and Dermatomyositis (ARTEMIS)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by Karolinska Institutet.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Institute of Rheumatology, Prague, Czech Republic
King's College Hospital NHS Trust
Information provided by:
Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT01315938
First received: March 15, 2011
Last updated: NA
Last verified: February 2010
History: No changes posted
  Purpose

The purpose of this study is to investigate the clinical efficacy of abatacept on disease activity in polymyositis, and dermatomyositis patients.


Condition Intervention Phase
Polymyositis
Dermatomyositis
Drug: Abatacept
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Abatacept Treatment in Polymyositis and Dermatomyositis

Resource links provided by NLM:


Further study details as provided by Karolinska Institutet:

Primary Outcome Measures:
  • The number of responders, defined as improved according the IMACS criteria [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The definition of improvement is based on a core set of clinical and laboratory variables to assess disease activity and outcome measure developed in an international consensus, partly validated and recommended for use in clinical trials by the IMACS group (26http://www.niehs.nih.gov/research/resources/collab/imacs). The improvement is defined as any 3 of 6 core set measures improved ≥ 20% with no more than 2 (not including MMT) worse by ≥ 25%.


Secondary Outcome Measures:
  • The change in the individual components of the IMACS core set measures for disease activity [ Time Frame: at 3 and 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: January 2011
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abatacept Drug: Abatacept
abatacept will be given as intravenous infusions at time 0 then after, 2, 4, 8, 12, 16 and 20 weeks.
Drug: Abatacept
Subjects will be treated with abatacept for 6 months and receive a total of up to 7 doses (intravenous infusions) the infusions will be given with the following intervals: at time 0 then after, 2, 4, 8, 12, 16 and 20 weeks.

Detailed Description:

Patients with polymyositis or dermatomyositis who have persisting signs of inflammatory active disease after treatment with glucocorticoids and at least one immunomodulating drug (e.g. methotrexate or azathioprine) for a minimum of 3 months.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with definite or probable polymyositis or dermatomyositis diagnosed according to the diagnostic criteria by Bohan and Peter (30,31).
  2. For polymyositis a muscle biopsy is required that confirmed this disease (performed at any time before the start of the study) and to exclude other conditions unless a patient is positive for myositis specific or myositis associated autoantibodies.
  3. Polymyositis will be included after a judicial process by the three PIs.
  4. Inflammatory active disease based on persisting or worsening muscle weakness, MMT < 150 or low endurance, FI -2 < 20% of upper value together with at least one other sign of active disease: elevated serum levels of muscle enzymes (CK, LD, ASAT, ALAT, above upper limit and being explained by muscle involvement and not eg liver disease), inflammation in recent muscle biopsy (< 3 months) or on MRI scans or active extramuscular disease: skin rash, arthritis or interstitial lung disease (ILD) (as suggested by chest X-ray, high resolution computerized tomography (HRCT), or pulmonary function test).
  5. Persisting disease activity after a minimum of 3 months treatment with prednisolone or equal drug. The treatment with prednisolone (or equal) should include the dose of at least 0.5 mg/kg/day for at least 1 month in the history and should be stable 1 month prior the baseline visit. Maximum dose of glucocorticoids should not exceed the equivalent of Prednisone 30 mg per day at the time of randomisation.
  6. Combination with at least one other immunosuppressive drug, which includes methotrexate (minimum dose 15 mg/week) or azathioprine (minimum dose 100 mg/day) for at least 3 months. The dose of methotrexate or azathioprine should be stable for at least 1 month before the first administration of abatacept.
  7. If methotrexate or azathioprine has had to be stopped or the dose decreased due to documented intolerance, lower dose or absence of these drugs is accepted provided this situation is stable for 1 month before the baseline.
  8. Age between 18 - 80 years.
  9. Signed informed consent.

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Exclusion Criteria:

  1. Patients with other types of inflammatory myopathies including

    • Drug induced myositis.
    • Inclusion body myositis
    • Malignancy associated myositis.
  2. Women who are pregnant or breastfeeding.
  3. Women with a positive pregnancy test on enrolment or prior to start of study drug administration.
  4. Women of Child Bearing age who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for 10 weeks after the last infusion of study medication.
  5. Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, ophthalmologic or cerebral disease with the exception of those symptoms that are a manifestation of polymyositis or dermatomyositis. Concomitant medical conditions that in the opinion of the investigator might place the subject at unacceptable risk for participation in this study.
  6. Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing. Patients with dermatomyositis need to be screened for malignancies according to routine procedures.
  7. Subjects who have a history of clinically significant drug or alcohol abuse. Subjects currently taking methotrexate who admit to consumption of more than an average of 1 alcoholic drink per day.
  8. Subjects with any serious bacterial infection (such as pneumonia, other renal infection and sinusitis), unless treated and resolved with antibiotics or chronic bacterial infection (such as pyelonephritis and chest infection with bronchiectasis) in the previous 3 months.
  9. Subjects with active tuberculosis requiring treatment within the previous 3 years. Subjects with a positive PPD at screening will not be eligible for the study unless they completed treatment for latent TB and have a negative chest x-ray at enrolment. A PPD response that is equal to or greater than 10 mm should be considered a positive test, although more conservative criteria may be applied as determined by the clinical circumstance and investigator according to published guidelines and/or local standards endorsed by the medical society. Quantiferon assay may replace PPD testing and patients are excluded from the study if the test is positive. Quantiferon positive patients who completed treatment for latent tuberculosis according to the local guidelines may be considered for enrolment.
  10. Subjects with herpes zoster that resolved less than 2 months prior to enrolment.
  11. Subjects with evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the time of potential enrolment, including subjects with evidence of Human Immunodeficiency Virus (HIV) infection.
  12. Significant toxicities associated with concomitant or previous immunosuppressive Therapy and anti-TNF therapy that would preclude subjects from participating and completing the study
  13. Patients with clinically apparent immunodeficiency syndrome, (IgA deficiency alone is not an exclusion criterion)
  14. Subjects with any of the following laboratory values:

    • Hgb < 8.5 g/dL.
    • WBC < 3,000/mm3 (3 x 109/L).
    • Platelets < 100,000/mm3 (100 x 109/L).
    • Serum creatinine > 2 times upper limit of normal.
    • Any other laboratory test results that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
  15. Subjects previously treated with rituximab: B cell levels are less than lower limit of normal as measured by Fluorescent Activated Cell Sorting (FACS) analysis.
  16. For all patients who have received prior rituximab, a normal CD19 B cell count must be documented at the time of screening for this study.
  17. Patients with Large granular lymphocyte (LGL) syndrome (to minimize the risk of including patients with high frequency of CD28 null T cells) that may not benefit from treatment.

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  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01315938

Contacts
Contact: Ingrid E Lundberg, MD, PhD +46851770000 ext 6087 Ingrid.Lundberg@ki.se
Contact: Maryam Dastmalchi, MD; PhD +46851770000 ext 1915 Maryam.Dastmalchi@karolinska.se

Locations
Czech Republic
Institute of Rheumatology Not yet recruiting
Prague, Czech Republic, 12850
Contact: Jiri Vencovsky, MD, PhD    +420224914469    venc@revma.cz   
Contact: Herman Mann, MD       mann@revma.cz   
Principal Investigator: Jiri Vencovsky, MD;PhD         
Sub-Investigator: Herman Mann, MD         
Sweden
Karolinska University Hospital Recruiting
Stockholm, Sweden, 17176
Contact: Ingrid E Lundberg, MD, PhD    +46851770000 ext 6087    Ingrid.Lundberg@ki.se   
Contact: Maryam Dastmalchi, MD, PhD    +46851770000 ext 1915    Maryam.Dastmalchi@karolinska.se   
Principal Investigator: Ingrid E Lundberg, MD,PhD         
Sub-Investigator: Maryam Dastmalchi, MD,PhD         
Sponsors and Collaborators
Karolinska Institutet
Institute of Rheumatology, Prague, Czech Republic
King's College Hospital NHS Trust
  More Information

No publications provided

Responsible Party: Ingrid E. Lundberg, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT01315938     History of Changes
Other Study ID Numbers: 2009-015957-20
Study First Received: March 15, 2011
Last Updated: March 15, 2011
Health Authority: Sweden: Medical Products Agency

Additional relevant MeSH terms:
Dermatomyositis
Polymyositis
Myositis
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Connective Tissue Diseases
Skin Diseases
Abatacept
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014