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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by Thomas Jefferson University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Gilead Sciences
Information provided by:
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01093885
First received: March 24, 2010
Last updated: NA
Last verified: March 2010
History: No changes posted
  Purpose

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


Condition Intervention
Systemic Sclerosis
Scleroderma
Drug: Ambrisentan with an anti-fibrotic agent to assess benefit on skin.

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study of Ambrisentan With Antifibrotic Agent Combination Therapy in Treatment of Diffuse Systemic Sclerosis

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • The primary objective of this study is to determine 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. [ Time Frame: Baseline, Month 1, 3, 6, 9, and Month 12. ] [ Designated as safety issue: Yes ]
    Using validated clinical response measurements such as the modified Rodnan skin score (MRSS) and scleroderma health assessment questionnaire (SHAQ), we will determine whether combination therapy will effect morbidity in systemic sclerosis.


Secondary Outcome Measures:
  • Secondary objectives will examine systemic sclerosis as it relates to visceral organ involvement based on the Medsger severity scale as well as quality of life as assessed by the Scleroderma health assessment questionnaire (SHAQ) and SF-36. [ Time Frame: Baseline, Month 1, 3, 6, 9, and 12 month. ] [ Designated as safety issue: Yes ]
    Using validated clinical response measurements such as the modified Rodnan skin score (MRSS)and scleroderma health assessment questionnaire (SHAQ), we will determine whether combination therapy will effect morbidity in systemic sclerosis.


Estimated Enrollment: 15
Study Start Date: February 2010
Estimated Study Completion Date: March 2012
Estimated Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
open label: medication Ambrisentan

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.

Drug: Ambrisentan with an anti-fibrotic agent to assess benefit on skin.

Drug is dispensed in tablet form.

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.

Other Names:
  • LETAIRIS (ambrisentan) tablets for oral use
  • Initial U.S. Approval: 2007

Detailed Description:

This is an open label, single center study to determine the efficacy and safety of ambrisentan and antifibrotic agent combination in systemic sclerosis. Up to twenty patients will be recruited within the next year who have early diffuse systemic sclerosis and are presently receiving treatment with any of the following antifibrotic agents - cellcept, colchicine, azathioprine, D-penicillamine, methotrexate or cyclophosphamide. Ambrisentan will be added to the present agent and then followed for 12 months.

Patients, male or female, > 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 (24), and diffuse cutaneous involvement based on the criteria of LeRoy et al

A thorough baseline evaluation will determine the extent and severity of systemic sclerosis in the individual patients using laboratory studies and the clinical evaluation. Monthly follow-ups will capture any safety issues related to the combination therapy based again on laboratory studies and clinical evaluation. At the six month and twelve month follow-up a thorough evaluation will again be undertaken to evaluate the extent and severity of the disorder. Event driven follow-ups will also take place to record and establish any safety issues that may arise. Clinical end-points will be the focus of this study.

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. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.

  Eligibility

Ages Eligible for Study:   19 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01093885

Contacts
Contact: Elizabeth T Grace, RN 215-955-5778 elizabeth.grace@jefferson.edu

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Chris Derk, MD, MSc    215-955-1410      
Principal Investigator: Chris Derk, MD         
Sponsors and Collaborators
Thomas Jefferson University
Gilead Sciences
Investigators
Principal Investigator: Chris Derk, MD, MSc Thomas Jefferson University
  More Information

No publications provided

Responsible Party: Chris Derk, MD, MSc, Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01093885     History of Changes
Other Study ID Numbers: Ambrj55501.
Study First Received: March 24, 2010
Last Updated: March 24, 2010
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Scleroderma, Diffuse
Scleroderma, Systemic
Sclerosis
Connective Tissue Diseases
Pathologic Processes
Skin Diseases

ClinicalTrials.gov processed this record on November 27, 2014