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

A Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Systemic Sclerosis

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.

Study Overview

• Status: Completed
• Conditions: Scleroderma, Systemic; Scleroderma, Diffuse
• Intervention / Treatment: Drug: Placebo; Drug: Abatacept

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: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abatacept; Abatacept (dosed based upon weight) administered intravenously (IV) on days 1, 15, 30 and monthly thereafter for a total of 7 doses.	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.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Modified Rodnan Skin Score	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).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral Aperture at Baseline and Month 6		Baseline; Month 6
Hand Extension at Baseline and Month 6		Baseline; Month 6
Digital Ulcerations at Baseline and Month 6		Baseline; Month 6
Change in Pulmonary Function Tests	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.	6 months
Change in Scleroderma Health Assessment Questionnaire	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).	6 months

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Eliza Farmer Chakravarty, Stanford University

Publications and helpful links

General 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(1):159. doi: 10.1186/s13075-015-0669-3.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: March 1, 2007
• First Submitted That Met QC Criteria: March 1, 2007
• First Posted (Estimate): March 2, 2007

Study Record Updates

• Last Update Posted (Actual): October 31, 2017
• Last Update Submitted That Met QC Criteria: September 28, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: 100 186