Abatacept in Juvenile Dermatomyositis (AID)
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|ClinicalTrials.gov Identifier: NCT02594735|
Recruitment Status : Recruiting
First Posted : November 3, 2015
Last Update Posted : March 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Dermatomyositis||Drug: Abatacept||Phase 4|
JDM is a chronic systemic autoimmune disease with a predominance of muscle and skin inflammation of unknown etiology and varying prognosis. Children with JDM unresponsive to corticosteroids or other immunosuppressive medications face poor clinical and functional outcome and suffer various sequelae of the disease. Abatacept is a fully human soluble recombinant protein consisting of the cytotoxic T cell Lymphocyte Antigen-4 (CTLA4) fused with Fc region of human IgG1 that has been modified to prevent complement fixation and antibody-dependent cellular cytotoxicity. Abatacept binds specifically to the CD80 (B7-1) and CD86 (B7-2) molecules, those expressed on antigen-presenting cells (APCs). Upon engagement of CTLA4 to CD80 or CD86, the resultant inhibition of signal transduction inhibits T cell activation.. The rationale for use of Abatacept in the therapy of JDM includes the expression of CTLA4, CD28, CD86, and CD40 on inflammatory cells of muscle biopsies of patients with DM, as well as CTLA4 and CD28 on muscle cells.
A patient's participation in this study will last approximately 24 weeks with possible extension to 48 weeks. At screening, participants will have a physical exam, muscle strength assessment, blood and urine collection, and chest x-ray; they will also be asked to complete several questionnaires. All participants will receive each week subcutaneous injection of Abatacept. Each injection will be given on an outpatient basis.
There will be a total of 6 study visits. All participants will visit the outpatient clinic at selected time points for muscle strength testing, a physical exam, disease activity measurements, blood and urine collection, and muscle MRI; they will also be asked to complete several questionnaires. During the study, participants will be monitored closely for improvement or worsening of their disease and for serious drug related side effects.
Eligibility Ages Eligible for Study: ≥ 7 years and older Genders Eligible for Study: Both Race/Ethnic Backgrounds Eligibility for Study: No restrictions
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Abatacept for the Treatment of Refractory Juvenile Dermatomyositis|
|Study Start Date :||November 2015|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
A patient's participation in this study will last approximately 24 weeks ( screening visit and 5 intervention visits) with possible extension to 48 weeks. At screening, participants will have a physical exam, muscle strength assessment, blood and urine collection, and chest x-ray; they will also be asked to complete several questionnaires. All participants will receive each week subcutaneous injection of Abatacept. During intervention phase of the trial, muscle strength testing, physical exam, disease activity measurements, blood and urine collection, and muscle MRI will be performed. Participants will also be asked to complete several questionnaires. Participants will be also monitored closely for for serious drug related side effects.
Study participation will consist of a screening visit and 5 protocol visits over six months (week 0, week 6, week 12, week 18, and week 24) for each subject, and phone follow-up (week 2, week 4, week 8, week 10, week 14, week 16, week 20, and week 22). At Visit 1, which will be treatment initiation, eligible subjects will be instructed on the use and side effects of subcutaneous abatacept and will be started on the study drug (abatacept 125 mg SQ weekly for subjects with body weight ≥ 50 KG or abatacept 87.5mg SQ for subjects with body weight < 50 KG).
Other Name: Orencia
- Number of patients meeting the definition of improvement (DOI) at week 24: at least 3 of 6 Core Set Measures (CSM) improved by ≥ 20% with no more than 2 CSM worsening by ≥ 25% (not including the manual muscle testing). [ Time Frame: week 0 to week 24 ]Improvement in myositis disease activity will be assessed using the IMACS myositis definition of improvement (DOI): at least 3 of 6 Core Set Measures (CSM) improved by ≥ 20% with no more than 2 CSM worsening by ≥ 25% (a worsening measure cannot be the manual muscle testing (MMT).
- Incidence of treatment-emergent adverse events. [ Time Frame: week 0 to week 24 ]Safety will be assessed by review of adverse events using NCI Common Terminology criteria version 4.0 June 2010. Particular attention to serious adverse events and infections will be given. An adverse event diary will be maintained throughout the study. Patient evaluations will include: vital sign measurement, physical examination, and laboratory parameters for hematology and routine chemistries
- Number of patients improving in Physician and Patient/Parent global activity measurement from baseline [ Time Frame: week 0 to week 24 ]Physician and Patient/Parent global activity will be measured using a visual analogue scale (VAS) from 1 to centimeters
- Number of patients with steroid-sparing benefit from baseline [ Time Frame: week 0 to week 24 ]
Patients who have achieved Definition of Improvement (DOI) at week 6 (visit 2) or at any point thereafter and is rated by their study physician as at least minimally improved, then tapering of corticosteroids may commence using a precise dose reduction schedule as follows:
For patients taking 40 to 60 mg daily, prednisone will be tapered by 10 mg ,For patients taking 20 to 35 mg daily, prednisone will be tapered by 5 mg. For patients taking 7.5 to 15 mg daily, prednisone will be tapered by 2.5 mg. For patients taking 1 to 5 mg daily, prednisone will be tapered by 1 mg For patients receiving intravenous pulse methylprednisolone therapy, they may alternatively reduce the dose of IV therapy, instead of oral by a decrease of 25%
- Number of patient with improvement in Muscle strength [ Time Frame: week 0 to week 24 ]Muscle strength will be measured using the Manual Muscle Testing (MMT). MMT is a quantitative testing of eight proximal, distal and axial muscle groups tested unilaterally (using a 0-10 point scale)
- Number of patient with improvement in cutaneous activity disease from baseline [ Time Frame: week 0 to week 24 ]Cutaneous activity will be measured using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) It measures activity and damage in the skin. It has 3 activity scales (erythema, scale, erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis). In addition, Gottron's papules on the hands are evaluated in terms of activity (erythema/ulceration) and damage (dyspigmentation or scarring). Activity in terms of periungal changes and alopecia is also measured. Each of the 3 activity scales and 2 damage measures is assessed over 15 body areas; the worst level of activity is scored, whereas the damage measures is scored for their presence or absence
- Number of patient with improvement in muscle inflammation from baseline [ Time Frame: week 0 to week 24 ]Muscle inflammation will be measured by examining a thigh/pelvis STIR MRI at baseline and 6 month follow-up. MRI readings will be blinded to the clinical assessment
- Number of patient developing HAHA (human anti-human) antibodies [ Time Frame: week 0 to week 24 ]The ELISA (enzyme-linked immunosorbent assay) technique will be used to detect HAHA
- Number of patients with improvement in physical function from baseline [ Time Frame: week 0 to 24 ]Physical function will be measured by using the Stanford HAQ/CHAQ: Health Assessment Questionnaire: The Stanford HAQ is a brief self-report questionnaire assessing physical function pertaining to activities of daily living in a variety of domains. The C-HAQ was adapted directly from the HAQ and it has also been successfully applied to patient with juvenile myositis.
- Number of patients with improvement in extra-muscular activity from baseline [ Time Frame: week 0 to 24 ]The extra-muscular activity will be measured by using the Myositis Disease Activity Assessment Tool (MDAAT) .MDAAT is a combined tool that captures the physician's assessment of disease activity of various organ systems using a 0 to 4 scale (0 = Not present in the last 4 weeks; 4 = New - in the last 4 weeks (compared to the previous 4 weeks)) and a visual analog scale (VAS) to capture the ongoing disease activity over the past 4 weeks for each organ system on the 0-10cm VAS scale
- Number of patients with improvement is muscle enzymes from baseline [ Time Frame: week 0 to 24 ]The muscle enzymes includes creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). If more than one muscle enzyme is identified as being elevated (a minimum level of 1.3 x the upper limit of normal), then the most abnormal will be selected and this enzyme will be the target enzyme followed to evaluate disease improvement or worsening.
- Number of patients with changes in biomarkers of disease activity [ Time Frame: week 0 to 24 ]The following biomarker of disease activity will be measured (blinded to the clinical assessment information and drug dose): i. Immunophenotyping for CD4, CXCR3, IFNγ (TH1), CD4, CCR4, CRTH2, IL4 (TH2), CD4, CCR6, IL17a (TH17), CD4, CD25, Foxp3 (T regulatory cells), B cell markers and macrophage markers along with B71, B72, CTLA4, CT28 on fresh lymphocytes ii. Isolation of T cells, B cells, dendritic cells, monocyte and macrophages, and freeze the isolated cells for subsequent molecular and functional analysis, including gene expression profiling iii. Cytokine 30-plex panel on serum samples iv. Peripheral blood mononuclear cells for RNA gene expression using a gene bead chip panel.
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): NCT02594735
|Contact: Rodolfo V Curiel, MD||(202)firstname.lastname@example.org|
|Contact: Sirlekar Bullocks||(202) email@example.com|
|United States, District of Columbia|
|2300 M Street, 9th floor. Medical Faculty Associates, The George Washington University.||Recruiting|
|Washington, District of Columbia, United States, 20037|
|Contact: Rodolfo V Curiel, MD 202-750-0377 firstname.lastname@example.org|
|Contact: Sirlekar Bullocks (202)-677-6141 email@example.com|
|Principal Investigator:||Rodolfo V Curiel, MD||The George Washington University|