Clinical Trial: Targeting Complement Activation in Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis - Eculizumab
Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional
Official Title: Targeting Complement Activation in Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis
Brief Summary:
The purpose of this research study is to see if Eculizumab (Soliris®) can safely be used in addition to conventional therapy in patients with active ANCA (Antineutrophil Cytoplasmic Autoantibodies ) vasculitis and lead to a more rapid decrease in disease activity.
ANCA vasculitis is an inflammation of the small vessels whereby ANCA antibodies inappropriately activate one's own white blood cells (neutrophils) and cause damage to the small blood vessels.
Detailed Summary:
Recent laboratory studies have identified that an important pathway of inflammation called the "complement pathway" may play an important role in how Antineutrophil Cytoplasmic Autoantibodies (ANCA) cause damage to the blood vessels. Eculizumab is a monoclonal antibody that targets a key component of the complement pathway named C5, and blocks its activation.
In a mouse model of ANCA vasculitis, it has been shown that blocking C5 activation can block the development of vasculitis or greatly reduce its severity.
The researchers in this study would like to see if taking eculizumab, in addition to the drugs usually used to treat ANCA vasculitis, would be beneficial in treating ANCA vasculitis.
Currently, the conventional treatment of ANCA vasculitis consists of corticosteroids and cyclophosphamide. The corticosteroids are given as by vein (methylprednisolone) for 3 days followed by prednisone by mouth daily for about 4-5 months. Cyclophosphamide is typically given by vein every 4 weeks for at least 3 months, but sometimes longer depending on whether the vasculitis is still active or not. After the vasculitis is in remission, a maintenance treatment with azathioprine or mycophenolate mofetil may be used. For patients who cannot tolerate cyclophosphamide, or who have received it in large doses previously, another medication called rituximab may be used instead. However, patients who need rituximab or have recently been treated with rituximab cannot participate in this study.
The study drug, eculizumab, is Food and Drug Administration (FDA) approved for indications other than ANCA vasculitis. It is an investigational drug and it is NOT FDA-approved for the treatment of ANCA vasculitis.
Change in disease activity as measured by BVAS at 12 weeks.
Original Primary Outcome: BVAS [ Time Frame: 12 weeks ]
Current Secondary Outcome:
- Complement levels elevation [ Time Frame: up to 52 weeks ]Evaluation of complement levels at study entry to determine which may be elevated in active disease (Bb, C3a, C3d, C3d/C3, C4d, C5a or C5b-9
- Birmingham Vasculitis Activity Score(BVAS) [ Time Frame: up to 52 weeks ]Percent of patients with a BVAS =0 at 3 months
- Normalisation of complement activation [ Time Frame: up to 52 weeks ]Normalization of complement activation at 4 weeks, 8, 12, 24, 36 and 52 weeks
- Change in complement levels [ Time Frame: from baseline to week 12 ]Change in complement levels between groups from baseline to week 12
- change in complement levels 2 [ Time Frame: up to 52 weeks ]Change in these complement levels with treatment and decrease in disease activity for each patient
- Birmingham Vasculitis Activity Score (BVAS) 2 [ Time Frame: up to 52 weeks ]Mean BVAS at 24, 36 and 52 weeks
Original Secondary Outcome: Complement levels , BVAS [ Time Frame: up to 52 weeks ]
Information By: University of North Carolina, Chapel Hill
Dates:
Date Received: December 13, 2010
Date Started: May 2011
Date Completion:
Last Updated: February 17, 2017
Last Verified: September 2016
