Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis

NCT00468208 | Completed Phase 1 Results DMC

• 2 other identifiers: RDCRN 5522U54AR057319
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

Wegener's granulomatosis (WG) is a rare disease that causes inflammation of blood vessels, or vasculitis. It may involve many different parts of the body, but typically affects the upper and lower respiratory tract and kidneys. The purpose of this study is to determine the safety and effectiveness of the medication abatacept in treating adults with mild relapsing WG.

Conditions

Wegener's Granulomatosis

Keywords

Vasculitis; Relapse; Wegener's; Treatment

Outcome Measures

Primary Outcomes (1)

• Safety of Abatacept - Number of Participants With Adverse Events

  This study examined the safety profile of this agent when used in Wegener's granulomatosis. Information was gathered on all adverse events with specific events being identified in the protocol for analysis that included the following: * Infection * Infusion reactions * Cytopenias * Transaminase elevation * Skin reactions * GI side effects * Malignancy All adverse events were reportable for this study.

  Measured continuously from the screening visit through to the 6 month post-treatment study visit, up to 3 years and 4 months.

Secondary Outcomes (4)

• Disease Remission

  Measured monthly until common closing or early termination,up to 3 years and 4 months.

• Disease Improvement

  Measured monthly until common closing or early termination, up to 3 years and 4 months.

• Meeting Common Closing

  Number assessed at the time of common closing, up to 3 years and 4 months.

• Disease Relapse

  Measured monthly until common closing or early termination, up to 3 years and 4 months.

Study Arms (1)

1

EXPERIMENTAL

Participants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and then once a month thereafter.

Drug: Abatacept

Interventions

Abatacept DRUG

A participant's abatacept dose depended on body weight and will remain the same throughout the study: * 500 mg of abatacept for body weight less than 60 kg * 750 mg of abatacept for body weight between 60 and 100 kg * 1000 mg of abatacept for body weight greater than 100 kg Abatacept is administered in a 30-minute intravenous infusion.

1

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of WG, meeting at least 2 of the 5 modified American College of Rheumatology (ACR) criteria. More information about this criterion can be found in the protocol.
• Relapse of WG within the past 28 days where disease activity is confined to one or more of the following sites and where the symptoms/signs are of such a nature that the usual treatment would consist of the reinstitution or increase in GC to no more than prednisone 30mg daily and/or an increase or addition of a second immunosuppressive agent other than CYC (more specific information about this criterion can be found in the protocol):
• Sinonasal disease
• Oral mucosa ulceration
• Skin disease
• Musculoskeletal disease
• Pulmonary parenchymal disease
• Mild ocular disease
• Subglottic inflammation without significant stenosis
• Otic disease
• Breast involvement
• Urogenital involvement
• Other mild disease
• Age of 15 years or older
• Willing and able to undergo treatment and attend follow-up visits

You may not qualify if:

• Disease involvement that does not meet the criteria for mild disease. More information about this criterion can be found in the protocol.
• Disease activity that would usually be treated first with cyclophosphamide
• Presence of disease activity for which the investigator would normally treat the participant with more than prednisone 30 mg daily.
• Receiving cyclophosphamide at study entry
• Treatment with prednisone at a dose of more than 15 mg daily at the time of relapse. Subjects will be eligible if prednisone was initiated or dose increased in the period between relapse and study enrollment provided that the prednisone dose was 15 mg daily or less at the time when the relapse occurred, the prednisone dosage was increased no higher than 30 mg daily following the recognition of relapse, and that the dosage increase was made no more than 28 days prior to enrollment.
• Active infection
• HIV infected, hepatitis C virus infected, or positive for hepatitis B
• Unable to follow through with study participation
• Cytopenia, defined as platelet count less than 80,000/mm3, absolute neutrophil count less than 1500/mm3, OR hematocrit less than 20%
• Kidney insufficiency
• Use of illegal drugs
• Any other uncontrolled disease that would prevent participation
• History of cancer. More information about this criterion can be found in the protocol.
• Received an investigational medication or procedure within 30 days of study entry
• Received a live vaccine within 4 weeks of study entry

Sponsors & Collaborators

• University of Pennsylvania: lead
• Office of Rare Diseases (ORD): collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• Rare Diseases Clinical Research Network: collaborator

Study Sites (4)

The Johns Hopkins Vasculitis Center

Baltimore, Maryland, 21224, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Mayo Clinic College of Medicine

Rochester, Minnesota, 55905, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (4)

• Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, Birbara C, Box J, Natarajan K, Nuamah I, Li T, Aranda R, Hagerty DT, Dougados M. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005 Sep 15;353(11):1114-23. doi: 10.1056/NEJMoa050524.

  PMID: 16162882 BACKGROUND

• Langford CA, Talar-Williams C, Barron KS, Sneller MC. Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rate of relapse. Am J Med. 2003 Apr 15;114(6):463-9. doi: 10.1016/s0002-9343(03)00077-9.

  PMID: 12727579 BACKGROUND

• Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. 2005 Jan 27;352(4):351-61. doi: 10.1056/NEJMoa041884.

  PMID: 15673801 BACKGROUND

• Langford CA, Monach PA, Specks U, Seo P, Cuthbertson D, McAlear CA, Ytterberg SR, Hoffman GS, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener's). Ann Rheum Dis. 2014 Jul;73(7):1376-9. doi: 10.1136/annrheumdis-2013-204164. Epub 2013 Dec 9.

  PMID: 24323392 RESULT

Related Links

• Cleveland Clinic Center for Vasculitis Care and Research website

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Vasculitis; Recurrence

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Limitations and Caveats

The main limitation of this trial is the small sample size and the open-label, uncontrolled design.

Results Point of Contact

• Title: Carol A Langford, MD MHS
• Organization: Vasculitis Clinical Research Consortium

langfoc@ccf.org

216-445-6056

Study Officials

• Carol A. Langford, MD, MHS

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• Peter A. Merkel, MD, MPH

  Boston University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2007
• First Posted: May 2, 2007
• Study Start: February 1, 2008
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: January 18, 2016
• Results First Posted: November 26, 2013

Record last verified: 2015-12

Locations

US (4)