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
|Condition or disease||Intervention/treatment||Phase|
|Scleroderma, Diffuse Scleroderma, Systemic||Drug: Abatacept Drug: Placebo||Phase 1 Phase 2|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||A Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Systemic Sclerosis|
|Study Start Date :||November 2008|
|Primary Completion Date :||June 2011|
|Study Completion Date :||June 2011|
Abatacept (dosed based upon weight) administered intravenously (IV) on days 1, 15, 30 and monthly thereafter for a total of 7 doses.
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.
- 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).
- 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).
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): NCT00442611
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|Principal Investigator:||Eliza Farmer Chakravarty||Stanford University|