Study of Ambrisentan With Antifibrotic Agent Combination Therapy in Diffuse Systemic Sclerosis

• Status: Completed
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Systemic sclerosis is a chronic autoimmune connective tissue disorder with no universally accepted disease modifying regimen. Recruiting patients for systemic sclerosis treatment studies is difficult due to the limited availability of such patients and furthermore the use of a placebo arm is often deemed unethical due to the poor survival of diffuse systemic sclerosis patients.

Long-term controlled trials examining functional outcomes and survival from novel therapeutic agents for systemic sclerosis are often difficult to undertake because of costs, rarity of the disease and ethical issues with the use of a true placebo. Open label single center studies while inferior to multicenter placebo controlled studies, have helped establish the benefits of certain pharmaceutical agents in systemic sclerosis, and while not universally accepted as disease modifying agents, have been used with some success to treat systemic sclerosis.

The hypothesis on which we are basing this study is that an endothelin receptor antagonist and disease modifying agent with antifibrotic properties will have additive influence on fibrosis, inhibit cellular and humoral hyperactivity and interfere with smooth muscle proliferation in the vessel wall. The combination of these two agents will also be the first regimen to address the heterogeneity of scleroderma manifestations including ILD, pulmonary arterial hypertension and skin manifestations

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborator: Gilead Sciences
• Treatments: Ambrisentan

Criteria

Inclusion Criteria:

Patients, male or female, greater than 18 years with a clinical diagnosis of systemic sclerosis fulfilling the criteria of the American College of Rheumatology (formerly the American Rheumatism Association) classification criteria for systemic sclerosis, and diffuse cutaneous involvement based on the criteria of LeRoy et al

• Onset of skin sclerosis less than or equal to 48 months before study entry.

• Extent of skin sclerosis involving the trunk and/or arms and legs proximally to the elbows and/or knees.

• Present regimen consisting of one of the following: cellcept, D-penicillamine, methotrexate or cyclophosphamide.

• Previous history of using an alternative antifibrotic agent prior to present regimen will be permitted.

• Total antifibrotic treatment regimen duration should be less than or equal to 48 months.

Exclusion Criteria:

• Systemic sclerosis with skin involvement confined to face or acral regions of the body.

• Chemically induced scleroderma.

• Diffuse fasciitis.

• Mixed connective tissue disease and overlap syndromes.

• Pregnancy or nursing.

• Use of non-reliable method of contraception.

• Major surgery in the past month.

• Inability or unwillingness to provide written informed consent.

• Inability or unwillingness to comply with the requirements of the protocol as determined by the investigator.

• Known hypersensitivity or contraindication to ambrisentan