Anti-Cytokine Therapy for Vasculitis

Microscopic Polyangiitis Clinical Trial

— ACTIVE  

Official title:

Phase II Pilot Cohort Study to Investigate the Safety and Efficacy of Infliximab as Additional Therapy in the Treatment if Anti-Neutrophil Cytoplasm Antibody Associated Vasculitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00753103
• Other study ID #: RRK2031
• Status: Completed
• Phase: Phase 2
• First received: September 15, 2008
• Last updated: September 15, 2008
• Start date: January 2003
• Est. completion date: July 2006

Study information

• Verified date: September 2008
• Source: University Hospital Birmingham NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether Infliximab (monoclonal anti-tumour necrosis factor alpha antibodies) are safe and effective in the treatment of anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis.

Description:

Anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis is a life-threatening systemic inflammatory autoimmune disease. Current treatment regimes using corticosteroids and cyclophosphamide have improved patient survival but are associated with treatment associated morbidity and mortality. Tumour necrosis factor alpha (TNF) is a proinflammatory cytokine which has been implicated in the pathogenesis of ANCA vasculitis. Anti-TNF therapies have been used successfully in the management of other inflammatory autoimmune diseases. This phase II cohort study has been designed to investigate the safety and efficacy of anti-TNF monoclonal antibody (Infliximab) therapy for patients with ANCA associated vasculitis when used in addition to standard immunosuppressive therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: July 2006
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Either newly diagnosed or relapsed ANCA associated vasculitis (Wegener's granulomatosis, microscopic polyangiitis, renal limited vasculitis)

Exclusion Criteria:

• Active infection

• Malignancy

• Pregnancy

• Diagnosis of Churg-Strauss syndrome or anti-glomerular basement membrane antibody disease

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Microscopic Polyangiitis
• Renal Limited Vasculitis
• Systemic Vasculitis
• Vasculitis
• Wegener Granulomatosis
• Wegener's Granulomatosis

Intervention

Biological:
• Infliximab
5 mg/kg intravenous infusion at weeks 0, 2, 6 and 10 of study

Drug:
• Cyclophosphamide
Daily oral 2 mg/kg or pulsed intravenous 15mg/kg every 2-3 weeks for 3-6 months (until patient has been in remission for 3 months).
• Prednisolone
Daily oral 1mg/kg tapered over 12 months
• Azathioprine
Daily oral 2 mg/kg started once patient is in remission and cyclophosphamide has been discontinued.

Procedure:
• Plasma exchange
Additional therapy for patients with severe vasculitis (creatinine > 500 mcmol/L or pulmonary haemorrhage). 7x 4L exchanges over 10 days.

Drug:
• Mycophenolate mofetil
Daily oral up to 1.5 g twice daily as tolerated. Used as alternative to azathioprine at lead physicians discretion.
• Methylprednisolone
500 mg intravenous infusion daily for three days at lead physicians discretion.

Locations

Country	Name	City	State
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham	West Midlands

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Birmingham NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to clinical remission (Birmingham Vasculitis Activity Score 0 or 1)		0, 6, 10, 14, 26, 39 and 52 weeks	No
Secondary	Adverse events		Weeks 2, 6, 10, 14, 26, 39, 52	Yes
Secondary	Vasculitis Damage Index Score		Weeks 0, 14, 26, 39, 52	No
Secondary	Renal function		Weeks 0, 2, 6, 10, 14, 26, 39, 52	No