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

NCT01093885 | Completed Results DMC

• 1 other identifier: Ambrj55501.
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Systemic Sclerosis; Scleroderma

Outcome Measures

Primary Outcomes (1)

• The Benefit That an Antifibrotic Agent and Ambrisentan Combination Have on the Cutaneous Involvement of Patients With Early Diffuse Systemic Sclerosis by Utilizing the MRSS

  Using validated clinical response measurements such as the modified Rodnan skin score (MRSS) we will determine whether combination therapy will effect morbidity in systemic sclerosis. The modified Rodnan skin score has a range from 0-51 with higher numbers being worse skin involvement.

  Baseline and 12 months

Secondary Outcomes (1)

• Systemic Sclerosis Quality of Life Assessed by the SF-36.

  Baseline vs Month 12.

Study Arms (1)

open label: medication Ambrisentan

OTHER

Open label study of Ambrisentan. Ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study. \*\* Dose escalation was attempted however none of the patients were able to increase. Therefore all subjects remained on 5 mg daily throughout the study. 12 patients on mycophenolate mofetil, 2 on mycophenolic acid and one on methotrexate

Drug: Ambrisentan

Interventions

Ambrisentan DRUG

Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.

Also known as: LETAIRIS (ambrisentan) tablets for oral use, Initial U.S. Approval: 2007

open label: medication Ambrisentan

Eligibility Criteria

• Age: 19 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Gilead Sciences: collaborator

Study Sites (1)

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Schorpion A, Shenin M, Neubauer R, Derk CT. A prospective, open-label, non-comparative study of ambrisentan with anti-fibrotic agent combination therapy in the treatment of diffuse systemic sclerosis. BMC Rheumatol. 2018 May 15;2:13. doi: 10.1186/s41927-018-0021-z. eCollection 2018.

  PMID: 30886964 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Diffuse

Interventions

ambrisentan; Tablets

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

Dose escalation was attempted however none of the patients were able to increase. Therefore all subjects remained on 5 mg daily throughout the study.

Results Point of Contact

• Title: Dr. Chris Derk
• Organization: University of Pennsylvania Health System

chris.derk@uphs.upenn.edu

215-662-2792

Study Officials

• Chris Derk, MD, MSc

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm open label study.

Study Record Dates

• First Submitted: March 24, 2010
• First Posted: March 26, 2010
• Study Start: February 1, 2010
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: November 29, 2018
• Results First Posted: November 29, 2018

Record last verified: 2018-11

Locations

US (1)