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A Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Diffuse Systemic Sclerosis (Scleroderma)

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ClinicalTrials.gov Identifier: NCT00442611
Recruitment Status : Completed
First Posted : March 2, 2007
Results First Posted : April 24, 2015
Last Update Posted : October 31, 2017
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Lorinda S Chung, Stanford University

Tracking Information
First Submitted Date  ICMJE March 1, 2007
First Posted Date  ICMJE March 2, 2007
Results First Submitted Date  ICMJE January 26, 2015
Results First Posted Date  ICMJE April 24, 2015
Last Update Posted Date October 31, 2017
Study Start Date  ICMJE November 2008
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2015)
Change in Modified Rodnan Skin Score [ Time Frame: 6 months ]
Modified Rodnan Skin Score measures skin thickness and is the sum of scores from 17 surface anatomic areas rated on a 0-3 scale (0=normal skin; 1=mild thickness; 2=moderate thickness; 3=severe thickness with inability to pinch the skin into a fold). Total modified Rodnan Skin Score ranges from 0 (best possible outcome) to 51 (worst possible outcome).
Original Primary Outcome Measures  ICMJE
 (submitted: March 1, 2007)
Change in Modified Rodnan Skin Score
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2017)
  • Oral Aperture at Baseline and Month 6 [ Time Frame: Baseline; Month 6 ]
  • Hand Extension at Baseline and Month 6 [ Time Frame: Baseline; Month 6 ]
  • Digital Ulcerations at Baseline and Month 6 [ Time Frame: Baseline; Month 6 ]
  • Change in Pulmonary Function Tests [ Time Frame: 6 months ]
    FVC (Forced Vital Capacity) is the amount of air that can be forcibly exhaled from the lungs after taking the deepest possible breath. DLCO (Diffusing capacity of the lung for carbon monoxide) is the extent to which oxygen passes from the lungs to the blood.
  • Change in Scleroderma Health Assessment Questionnaire [ Time Frame: 6 months ]
    The HAQ Disability Index (HAQ-DI) includes 20 items in 8 functional domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities) assessing the patient's usual abilities in the past seven days. Each item is scored on a 0-3 scale (0=without any difficulty; 1=with some difficulty; 2=with much difficulty; 3=unable to do). The use of assistive devices for any domain increases the domain score by 1 point to a maximum of 3. The overall score is calculated by summing the highest item score in each of the domains and dividing the sum by 8, with an overall score of 0 indicating no disability, and a score of 3 indicating severe disability. The time points compared were 6 months to baseline (6 months minus baseline).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2007)
  • Change in Oral Aperture and Hand Extension
  • Change in Pulmonary Function Tests
  • Change in Digital Ulcerations
  • Scleroderma Health Assessment Questionnaire
  • Change in Serum Autoantibody Profile
  • Change in Serum Cytokine Profile
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Diffuse Systemic Sclerosis (Scleroderma)
Official Title  ICMJE A Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Systemic Sclerosis
Brief Summary Systemic sclerosis (scleroderma) is an autoimmune connective tissue disease that involves the skin and other internal organs for which there are few effective treatment options. We hypothesize that treatment with abatacept, a new therapy recently approved for the treatment of rheumatoid arthritis, may reduce the progression of skin thickening and fibrosis in people with scleroderma.
Detailed Description

Systemic sclerosis is an autoimmune connective tissue disease of unknown etiology characterized by progressive fibrosis of the skin and internal organs, vascular damage, and autoantibody production. Although the disease is relatively rare, it is associated with considerable morbidity and mortality. There have been improvements in survival over the past few decades; however, this has been related to better management of vascular manifestations of disease including renal crisis, pulmonary hypertension, gastroesophageal reflux disease, and Raynaud's phenomenon. Clinical studies of disease modifying therapies for cutaneous disease to date have been relatively unsuccessful.

Although the etiology of the disease remains unknown, several observations support the role of activated T cells in both the blood and skin of affected patients. Abatacept, a recombinant fusion protein that blocks T cell activation, has recently been approved by the FDA for rheumatoid arthritis. We hypothesize that inhibition of T cell activation with abatacept may be efficacious in the treatment of patients with diffuse systemic sclerosis. This is a randomized, double-blinded, placebo-controlled clinical trial of abatacept versus placebo in patients with diffuse systemic sclerosis. Changes in validated measures of skin thickness and disease activity over 6-months of treatment will be compared between patients receiving abatacept and those receiving placebo. Patients will be randomized 2:1 to receive abatacept.

The protocol was amended during the study and the outcome measures "Change in Serum Autoantibody Profile" and "Change in Serum Cytokine Profile" were changed to exploratory outcomes.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Scleroderma, Diffuse
  • Scleroderma, Systemic
Intervention  ICMJE
  • Drug: Abatacept
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Abatacept
    Abatacept (dosed based upon weight) administered intravenously (IV) on days 1, 15, 30 and monthly thereafter for a total of 7 doses.
    Intervention: Drug: Abatacept
  • Placebo Comparator: IV fluid
    Placebo to match abatacept (IV fluid) administered on days 1, 15, 30 and monthly thereafter for a total of 7 doses.
    Intervention: Drug: Placebo
Publications * Chakravarty EF, Martyanov V, Fiorentino D, Wood TA, Haddon DJ, Jarrell JA, Utz PJ, Genovese MC, Whitfield ML, Chung L. Gene expression changes reflect clinical response in a placebo-controlled randomized trial of abatacept in patients with diffuse cutaneous systemic sclerosis. Arthritis Res Ther. 2015 Jun 13;17:159. doi: 10.1186/s13075-015-0669-3.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: July 20, 2011)
10
Original Enrollment  ICMJE
 (submitted: March 1, 2007)
12
Actual Study Completion Date  ICMJE June 2011
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of diffuse systemic sclerosis
  • age 18 years or older
  • Adequate renal, pulmonary, and cardiovascular function
  • Willingness to use effective contraception for the duration of the study if subject is of childbearing potential


Exclusion Criteria:

  • Other connective tissues diseases or overlap syndromes including MCTD, SLE, RA, eosinophilic fasciitis, and limited systemic sclerosis or morphea
  • Use of disease modifying agents including methotrexate, cyclosporine,azathioprine, mycophenolate mofetil, minocycline, doxycycline, minocycline, thalidomide, penicillamine, tamoxifen, colchicine, or investigational agent within 90 days of screening visit
  • HIV, Hepatitis B or Hepatitis C infection
  • use of prednisone greater than 10mg daily for 28 days prior to screening visit
  • women who are breastfeeding or pregnant
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00442611
Other Study ID Numbers  ICMJE 100 186
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Lorinda S Chung, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Eliza Farmer Chakravarty Stanford University
PRS Account Stanford University
Verification Date September 2017

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