Abatacept in ANCA Associated Vasculitis (ABAVAS)

Tracking Information
First Submitted Date ICMJE	June 1, 2007
First Posted Date ICMJE	June 4, 2007
Last Update Posted Date	May 29, 2015
Study Start Date ICMJE	November 2007
Actual Primary Completion Date	November 2008 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 1, 2007)	Relapse rate over 24 months. [ Time Frame: 2 years ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00482066 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 1, 2007)	Proportion of patients in sustained remission (i.e. remission at 3 months sustained for 6 months and remission at 6 months sustained for a further 12 months); [ Time Frame: 2 years ]; Time to remission; [ Time Frame: 2 years ]; The average steroid dosage at 6 months, 1 year, 18 months and 2 years in abatacept and placebo groups respectively; [ Time Frame: 2 years ]; Time to ANCA negativity by immunofluorescence or negative anti-PR3 or anti-MPO Ab test by ELISA. [ Time Frame: 2 years ]; Proportion of patients defaulting to cyclophosphamide (MMF, azathioprine or other rescue) therapy. [ Time Frame: 2 years ]; Proportion of patients unable to stick with trial protocol. [ Time Frame: 2 years ]; Degree of chronic disease activity [ Time Frame: 2 years ]; Health related quality of life [ Time Frame: 2 years ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Abatacept in ANCA Associated Vasculitis
Official Title ICMJE	A Pilot Study Examining the Effect of Abatacept in ANCA Associated Vasculitis
Brief Summary	The purpose of this study is to investigate whether abatacept can prevent relapse in patients with ANCA associated vasculitis(AAV). This is a randomised double blinded placebo controlled trial.
Detailed Description	The drugs that are normally used to treat patients with AAV are quite effective, but up to 20% of patients relapse within 18 months. The drugs used can also have significant side effects. Abatacept, also known as CTLA4Ig, acts by blocking vital costimulatory signals required for T lymphocytes to be activated. As ANCA associated vasculitis is believed to be an autoimmune condition and dependent on autoreactive T cells, there is some reason to believe this drug would be effective. Abatacept has already received a license by the FDA for use in Rheumatoid arthritis where it has proven to be effective even in patients unresponsive to Etanercept (TNF blockade). 120 patients with AAV will be invited to take part in this study, from hospitals in the UK and Europe. The patients will receive standard therapy with methotrexate and steroids as well as 12 months of abatacept or placebo. They will be followed for a further 12 months. The primary objective of this study is to assess the relapse rate over 24 months, in patients with acute AAV, presenting at first diagnosis or relapse, in the two arms of the study.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
Condition ICMJE	ANCA-associated Vasculitis
Intervention ICMJE	Drug: Abatacept (Orencia); 500mg for patients under 60kg 750mg for patients 60-100kg 1g for patients>100kg given as i.v. infusion over 30 minutes at day 0, 14, 28 and then monthly for a further 11 months 914 infusions in total) placebo groups receive saline only I.v.
Study Arms	Active Comparator: 1 Abatacept (Orencia) Intervention: Drug: Abatacept (Orencia); Placebo Comparator: 2 saline placebo Intervention: Drug: Abatacept (Orencia)
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: May 25, 2010)	7
Original Estimated Enrollment ICMJE; (submitted: June 1, 2007)	112
Actual Study Completion Date	November 2008
Actual Primary Completion Date	November 2008 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Acute AAV, presenting at first diagnosis or relapse, defined by clinical presentation; ANCA positivity (anti-MPO or anti-PR3 positive); BVAS score of > 8. Exclusion Criteria: Severe life-threatening disease, i.e. lung haemorrhage at the time of presentation, renal impairment with SCr>150 micromol/l, or severe CNS dysfunction thought to be due to vasculitis.; Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological or cerebral disease, or other medical conditions that might place the subject at unacceptable risk for participation in this study.; Any other non-vasculitic multisystem autoimmune disease; Serious acute or bacterial infection unless treated and completely resolved with antibiotics prior to enrolment; With any severe chronic or recurrent bacterial infection; With Hepatitis B or C or HIV; With Herpes zoster infection that resolved less than 2 months prior to enrolment; Subjects who have received any live vaccines within 3 months of the first dose of study medication or who will have need of a live vaccine at any time in the year following enrolment; Subjects with current clinical or laboratory evidence of active or latent tuberculosis (TB) and subjects with a history of active TB treated within the last 3 years; With any previous malignancy, with the exception of non-melanoma skin malignancies, adequately treated previously; Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional evaluations. Mammograms (females only) must be performed within 6 months of study entry or if documentation is not on file.; With MTX treatment in prior 3 months; Subjects with prior therapy with rituximab, anti-TNF therapy, or IL-1 receptor antagonists within last year or cyclophosphamide within last six months; Subjects with a history of intolerance to methotrexate; Subjects who have at any time received treatment with abatacept; Subjects who have received treatment with any investigational drug within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose; Subject receiving approved or investigational biologics; Subjects with any of the following laboratory values: Hgb < 8.5 g/dL. WBC < 3,000/mm3 (3 x 109/L) Platelets < 100,000/mm3 (100 x 109/L). Serum ALT or AST > 2 times upper limit of normal. Any other laboratory test results that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.; Subjects participating concurrently in another clinical trial; Pregnancy, breast feeding or inadequate contraception if female.; Allergy to a study medication
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United Kingdom
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00482066
Other Study ID Numbers ICMJE	cro632; 2006-001859-35 ( EudraCT Number ); BMS protocol No: IST110 ( Other Grant/Funding Number: Bristol Myers Squib funder )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Imperial College London
Study Sponsor ICMJE	Imperial College London
Collaborators ICMJE	Bristol-Myers Squibb
Investigators ICMJE	Study Director: Alan Salama Imperial College London
PRS Account	Imperial College London
Verification Date	March 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP