A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis

ANCA-Associated Vasculitis Clinical Trial

— ADVOCATE  

Official title:

A Randomized, Double-Blind, Active-Controlled, Phase 3 Study to Evaluate the Safety and Efficacy of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis Treated Concomitantly With Rituximab or Cyclophosphamide/Azathioprine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02994927
• Other study ID #: CL010_168
• Secondary ID: ADVOCATE
• Status: Completed
• Phase: Phase 3
• Start date: March 15, 2017
• Est. completion date: November 1, 2019

Study information

• Verified date: January 2024
• Source: ChemoCentryx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to evaluate the efficacy of CCX168 (avacopan) to induce and sustain remission in patients with active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), when used in combination with cyclophosphamide followed by azathioprine, or in combination with rituximab.

Description:

Complement 5a and its receptor C5aR (CD88) are involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This is a randomized, double-blind, active-controlled Phase 3 study to evaluate the safety and efficacy of the orally-administered, selective C5aR inhibitor CCX168 (avacopan) in inducing and sustaining remission in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated concomitantly with Rituximab or Cyclophosphamide/Azathioprine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 331
• Est. completion date: November 1, 2019
• Est. primary completion date: September 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Clinical diagnosis of granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis
• Male and female subjects, aged at least 18 years, with newly-diagnosed or relapsed associated vasculitis (AAV) where treatment with cyclophosphamide or rituximab is needed; where approved by Regulatory Agencies, adolescents (12-17 year old) may be enrolled
• Use of adequate contraception
• Positive test for anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO)
• At least 1 major item, or at least 3 non-major items, or at least the 2 renal items of proteinuria and hematuria on Birmingham Vasculitis Activity Score (BVAS)
• Estimated glomerular filtration rate =15 mL/minute/1.73 m^2 at screening

Exclusion Criteria:

• Pregnant or breast-feeding
• Alveolar hemorrhage requiring pulmonary ventilation support at screening
• Any other known multi-system autoimmune disease
• Required dialysis or plasma exchange within 12 weeks prior to screening
• Have a kidney transplant
• Received cyclophosphamide within 12 weeks prior to screening; if on azathioprine, mycophenolate mofetil or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1
• Received intravenous glucocorticoids, >3000 mg methylprednisolone equivalent, within 4 weeks prior to screening
• Have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening
• Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred (i.e., CD19 count > 0.01x10^9/L); received anti-tumor necrosis factor (TNF) treatment, abatacept, alemtuzumab, intravenous immunoglobulin (IVIg), belimumab, tocilizumab, or eculizumab within 12 weeks prior to screening
• For patients scheduled to receive cyclophosphamide treatment, urinary outflow obstruction, active infection (especially varicella zoster infection), or platelet count <50,000/µL before start of dosing
• Participated previously in a CCX168 study

Related Conditions & MeSH terms

• ANCA-Associated Vasculitis
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Vasculitis

Intervention

Drug:
• Avacopan
Avacopan 30 mg twice daily orally for 52 weeks (364 days): - Three 10 mg avacopan capsules in the morning, preferably with food, and three in the evening, preferably with food, approximately 12 hours after the morning dose. Oral prednisone-matching placebo tapering regimen over 20 weeks (140 days): Prednisone-matching placebo capsules equivalent to 60 mg per day if the subject's body weight was =55 kg, or 45 mg per day if the subject's body weight was <55 kg, starting on Day 1 with tapering according to a protocol-specified schedule. Adolescents who weighed =37 kg started at a prednisone-matching placebo dose of 30 mg per day.
• Prednisone
Avacopan-matching placebo twice daily orally for 52 weeks (364 days): - Three avacopan-matching placebo capsules in the morning, preferably with food, and three in the evening, preferably with food, approximately 12 hours after the morning dose. Oral prednisone tapering regimen over 20 weeks (140 days): Prednisone 60 mg per day if the subject's body weight was =55 kg, or 45 mg per day if the subject's body weight was <55 kg, starting on Day 1 with tapering according to the protocol-specified schedule. Adolescents who weighed =37 kg started at a prednisone dose of 30 mg per day.
• Cyclophosphamide
Orally or intravenously administered

Biological:
• Rituximab
Intravenously administered

Drug:
• Azathioprine
Orally administered

Locations

Country	Name	City	State
Australia	Clinical Trial Site	Adelaide
Australia	Clinical Trial Site	Auchenflower
Australia	Clinical Trial Site	Brisbane
Australia	Clinical Trial Site	Clayton
Australia	Clinical Trial Site	Concord
Australia	Clinical Trial Site	Heidelberg
Australia	Clinical Trial Site	Liverpool
Australia	Clinical Trial Site	Nambour
Australia	Clinical Trial Site	Nedlands
Australia	Clinical Trial Site	Randwick
Australia	Clinical Trial Site	Saint Albans
Australia	Clinical Trial Site	Southport
Australia	Clinical Trial Site	St Leonards
Australia	Clinical Trial Site	Westmead
Australia	Clinical Trial Site	Woolloongabba
Austria	Clinical Trial Site	Feldkirch
Austria	Clinical Trial Site	Graz
Austria	Clinical Trial Site	Innsbruck
Belgium	Clinical Trial Site	Antwerp
Belgium	Clinical Trial Site	Brussels
Belgium	Clinical Trial Site	Leuven
Belgium	Clinical Trial Site	Liège
Canada	Clinical Trial Site	Calgary
Canada	Clinical Trial Site	Greenfield Park
Canada	Clinical Trial Site	Hamilton
Canada	Clinical Trial Site	Montréal
Canada	Clinical Trial Site	Québec
Canada	Clinical Trial Site	Sherbrooke
Canada	Clinical Trial Site	Toronto
Canada	Clinical Trial Site	Vancouver
Czechia	Clinical Trial Site	Olomouc
Czechia	Clinical Trial Site	Praha
Denmark	Clinical Trial Site	Aalborg
Denmark	Clinical Trial Site	Aarhus
Denmark	Clinical Trial Site	Copenhagen
Denmark	Clinical Trial Site	Odense
Denmark	Clinical Trial Site	Roskilde
France	Clinical Trial Site	Angers
France	Clinical Trial Site	Bordeaux
France	Clinical Trial Site	Boulogne-sur-Mer
France	Clinical Trial Site	Brest
France	Clinical Trial Site	Bron
France	Clinical Trial Site	Caen
France	Clinical Trial Site	Colmar
France	Clinical Trial Site	Grenoble
France	Clinical Trial Site	Marseille
France	Clinical Trial Site	Metz
France	Clinical Trial Site	Nantes
France	Clinical Trial Site	Nîmes
France	Clinical Trial Site	Paris
France	Clinical Trial Site	Toulouse
France	Clinical Trial Site	Valenciennes
Germany	Clinical Trial Site	Aachen
Germany	Clinical Trial Site	Bad Bramstedt
Germany	Clinical Trial Site	Berlin
Germany	Clinical Trial Site	Cologne
Germany	Clinical Trial Site	Dresden
Germany	Clinical Trial Site	Essen
Germany	Clinical Trial Site	Freiburg
Germany	Clinical Trial Site	Fulda
Germany	Clinical Trial Site	Hamburg
Germany	Clinical Trial Site	Hannover
Germany	Clinical Trial Site	Heidelberg
Germany	Clinical Trial Site	Jena
Germany	Clinical Trial Site	Kirchheim unter Teck
Germany	Clinical Trial Site	Leipzig
Germany	Clinical Trial Site	Lübeck
Germany	Clinical Trial Site	Ludwigshafen
Germany	Clinical Trial Site	Mannheim
Germany	Clinical Trial Site	Munich
Germany	Clinical Trial Site	Tuebingen
Germany	Clinical Trial Site	Villingen-Schwenningen
Hungary	Clinical Trial Site	Budapest
Hungary	Clinical Trial Site	Debrecen
Ireland	Clinical Trial Site	Cork
Ireland	Clinical Trial Site	Dublin
Italy	Clinical Trial Site	Ancona
Italy	Clinical Trial Site	Firenze
Italy	Clinical Trial Site	Genova
Italy	Clinical Trial Site	Milano
Italy	Clinical Trial Site	Monza
Italy	Clinical Trial Site	Parma
Italy	Clinical Trial Site	Reggio Emilia
Italy	Clinical Trial Site	Torino
Italy	Clinical Trial Site	Udine
Japan	Clinical Trial Site	Aichi
Japan	Clinical Trial Site	Akita
Japan	Clinical Trial Site	Chiba
Japan	Clinical Trial Site	Hiroshima
Japan	Clinical Trial Site	Hokkaido
Japan	Clinical Trial Site	Ishikawa
Japan	Clinical Trial Site	Kagawa
Japan	Clinical Trial Site	Kanagawa
Japan	Clinical Trial Site	Kobe
Japan	Clinical Trial Site	Miyazaki
Japan	Clinical Trial Site	Nagoya
Japan	Clinical Trial Site	Okayama
Japan	Clinical Trial Site	Osaka
Japan	Clinical Trial Site	Saitama
Japan	Clinical Trial Site	Shimane
Japan	Clinical Trial Site	Shizuoka
Japan	Clinical Trial Site	Tokyo
Japan	Clinical Trial Site	Toyama
Japan	Clinical Trial Site	Yokohama
Netherlands	Clinical Trial Site	Groningen
Netherlands	Clinical Trial Site	Leiden
Netherlands	Clinical Trial Site	Rotterdam
New Zealand	Clinical Trial Site	Christchurch
New Zealand	Clinical Trial Site	Dunedin
New Zealand	Clinical Trial Site	Grafton
New Zealand	Clinical Trial Site	Hamilton
New Zealand	Clinical Trial Site	Takapuna
Norway	Clinical Trial Site	Nordbyhagen
Norway	Clinical Trial Site	Oslo
Norway	Clinical Trial Site	Tromsø
Spain	Clinical Trial Site	Badalona
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Burela
Spain	Clinical Trial Site	Lleida
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	San Sebastián
Sweden	Clinical Trial Site	Linköping
Sweden	Clinical Trial Site	Lund
Sweden	Clinical Trial Site	Örebro
Sweden	Clinical Trial Site	Stockholm
Sweden	Clinical Trial Site	Uppsala
Switzerland	Clinical Trial Site	Basel
Switzerland	Clinical Trial Site	Bern
Switzerland	Clinical Trial Site	Fribourg
Switzerland	Clinical Trial Site	Lausanne
Switzerland	Clinical Trial Site	St. Gallen
Switzerland	Clinical Trial Site	Zürich
United Kingdom	Clinical Trial Site	Aberdeen
United Kingdom	Clinical Trial Site	Basildon
United Kingdom	Clinical Trial Site	Birmingham
United Kingdom	Clinical Trial Site	Bristol
United Kingdom	Clinical Trial Site	Cambridge
United Kingdom	Clinical Trial Site	Canterbury
United Kingdom	Clinical Trial Site	Cardiff
United Kingdom	Clinical Trial Site	Carshalton
United Kingdom	Clinical Trial Site	Dorchester
United Kingdom	Clinical Trial Site	Dudley
United Kingdom	Clinical Trial Site	Exeter
United Kingdom	Clinical Trial Site	Glasgow
United Kingdom	Clinical Trial Site	Inverness
United Kingdom	Clinical Trial Site	Kirkcaldy
United Kingdom	Clinical Trial Site	Leeds
United Kingdom	Clinical Trial Site	Leicester
United Kingdom	Clinical Trial Site	Liverpool
United Kingdom	Clinical Trial Site	London
United Kingdom	Clinical Trial Site	Manchester
United Kingdom	Clinical Trial Site	Newcastle
United Kingdom	Clinical Trial Site	Nottingham
United Kingdom	Clinical Trial Site	Oxford
United Kingdom	Clinical Trial Site	Reading
United Kingdom	Clinical Trial Site	Salford
United Kingdom	Clinical Trial Site	Westcliff-on-Sea
United States	Clinical Trial Site	Ann Arbor	Michigan
United States	Clinical Trial Site	Atlanta	Georgia
United States	Clinical Trial Site	Aurora	Colorado
United States	Clinical Trial Site	Baltimore	Maryland
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Chapel Hill	North Carolina
United States	Clinical Trial Site	Charleston	South Carolina
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Cleveland	Ohio
United States	Clinical Trial Site	Columbus	Ohio
United States	Clinical Trial Site	Dallas	Texas
United States	Clinical Trial Site	Daytona Beach	Florida
United States	Clinical Trial Site	Duncansville	Pennsylvania
United States	Clinical Trial Site	Great Neck	New York
United States	Clinical Trial Site	Greenville	North Carolina
United States	Clinical Trial Site	Houston	Texas
United States	Clinical Trial Site	Huntsville	Alabama
United States	Clinical Trial Site	Indianapolis	Indiana
United States	Clinical Trial Site	Kansas City	Kansas
United States	Clinical Trial Site	Lexington	Kentucky
United States	Clinical Trial Site	Los Angeles	California
United States	Clinical Trial Site	Meridian	Idaho
United States	Clinical Trial Site	Mineola	New York
United States	Clinical Trial Site	Minneapolis	Minnesota
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Philadelphia	Pennsylvania
United States	Clinical Trial Site	Phoenix	Arizona
United States	Clinical Trial Site	Phoenix	Arizona
United States	Clinical Trial Site	Pittsburgh	Pennsylvania
United States	Clinical Trial Site	Providence	Rhode Island
United States	Clinical Trial Site	Rochester	Minnesota
United States	Clinical Trial Site	Saint Louis	Missouri
United States	Clinical Trial Site	Salt Lake City	Utah
United States	Clinical Trial Site	Santa Monica	California
United States	Clinical Trial Site	Seattle	Washington
United States	Clinical Trial Site	Shreveport	Louisiana
United States	Clinical Trial Site	Tampa	Florida
United States	Clinical Trial Site	Washington	District of Columbia
United States	Clinical Trial Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
ChemoCentryx

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Ireland,  Italy,  Japan,  Netherlands,  New Zealand,  Norway,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects Achieving Disease Remission at Week 26	Disease remission at Week 26 was defined as: Achieving a BVAS of 0 as determined by the Adjudication Committee; No administration of glucocorticoids given for ANCA-associated vasculitis within 4 weeks prior to Week 26; No BVAS >0 during the 4 weeks prior to Week 26 (if collected for an unscheduled assessment).	Week 26
Primary	Percentage of Subjects Achieving Sustained Disease Remission at Week 52	Sustained remission at Week 52 was defined as: Disease remission at Week 26 as defined above; Disease remission at Week 52 defined as a BVAS of 0 at Week 52 as determined by the Adjudication Committee and no administration of glucocorticoids for treatment of ANCA-associated vasculitis within 4 weeks prior to Week 52; No disease relapse between Week 26 and Week 52 as determined by the Adjudication Committee.	Week 52
Secondary	Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs	AEs=Adverse events; SAEs=Serious adverse events; TEAE=Treatment-emergent adverse event	From day 1 throughout the study period (day 421/week 60)
Secondary	Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI	GTI-CWS=Glucocorticoid Toxicity Index Cumulative Worsening Score; GTI-AIS=Glucocorticoid Toxicity Index Aggregate Improvement Score; The Glucocorticoid Toxicity Index (GTI) was developed to score glucocorticoid toxicity. The GTI includes: the Cumulative Worsening Score (CWS) that captures cumulative toxicity, both permanent and transient, over the course of time (serves as a cumulative record of toxicity); and the Aggregate Improvement Score that captures both improvement and worsening of toxicity over time (serves as a record of both improving and worsening toxicity). Both scores range from 0 (best health) to 100 (worst health).	Baseline, Week 13 and 26
Secondary	Percentage of Participants With BVAS of 0 at Week 4, Regardless of Whether the Subjects Received Glucocorticoids During This Period of Time and Based on Assessment by the Blinded AC	AC=Adjudication Committee; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).	Week 4
Secondary	Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index	SF-36v2: Measure of health- related quality of life (Medical Outcomes Survey Short Form-36 version 2); EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels; The SF-36v2 component scores and the EQ-5D-5L VAS score range from 0 (worst health) to 100 (best health). The EQ-5D-5L Index Score ranges from 0 (worst health) to 1 (best health).	Baseline, Week 26 and 52
Secondary	Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving Remission at Week 26 in the Study	The median time to relapse was not estimable because of small number of relapsed subjects.; A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or; having achieved BVAS=0 at any time during the treatment period; ANCA=anti-neutrophil cytoplasmic autoantibody; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).	Week 52
Secondary	Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving BVAS=0 at Any Time During the Treatment Period	The median time to relapse was not estimable because of small number of relapsed subjects.; A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or; having achieved BVAS=0 at any time during the treatment period; The Birmingham Vasculitis Activity Score (BVAS) form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).	Week 52
Secondary	In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks	Change from baseline in kidney function, as measured by eGFR (based on the MDRD equation), was measured in subjects with renal disease based on the BVAS renal component.; eGFR=estimated glomerular filtration rate; BVAS=Birmingham Vasculitis Activity Score; MDRD=Modification of Diet in Renal Disease	Baseline, Week 26 and 52
Secondary	In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks	BVAS=Birmingham Vasculitis Activity Score; UACR=Urinary albumin:creatinine ratio	Baseline, Week 4, 26 and 52
Secondary	In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks	BVAS=Birmingham Vasculitis Activity Score; MCP-1=monocyte chemoattractant protein-1	Baseline, Week 26 and 52
Secondary	Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points	VDI=Vasculitis Damage Index; The VDI is comprised of 64 items of damage, grouped into 11 organ-based systems or categorizations. Damage is defined as the presence of non-healing scars and does not give any indication of current disease activity. Damage is also defined as having been present or currently present for at least 3 months. Completion of the form provides a numerical score, which ranges from 0 (best health) to 64 (worst health).	Baseline, Week 26 and 52
Secondary	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5)		Baseline, Week 26 and 52
Secondary	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5)		Baseline, Week 26 and 52
Secondary	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5)		Baseline, Week 26 and 52
Secondary	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5)		Baseline, Week 26 and 52
Secondary	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5)		Baseline, Week 26 and 52
Secondary	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2)		Baseline, Week 26 and 52
Secondary	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2)		Baseline, Week 26 and 52
Secondary	Change From Baseline in Vital Signs (1/5)		Baseline, Week 26 and 52
Secondary	Change From Baseline in Vital Signs (2/5)		Baseline, Week 26 and 52
Secondary	Change From Baseline in Vital Signs (3/5)		Baseline, Week 26 and 52
Secondary	Change From Baseline in Vital Signs (4/5)		Baseline, Week 26 and 52
Secondary	Change From Baseline in Vital Signs (5/5)	BMI=Body Mass Index	Baseline, Week 26 and 52
Secondary	Number of Subjects With Clinically Significant ECG Changes From Baseline	Clinical significance was assessed by the individual reading of the ECGs; ECG=Electrocardiogram	From day 1 throughout the study period (day 421/week 60)
Secondary	Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator	AE=Adverse Event	From day 1 throughout the study period (day 421/week 60)
Secondary	Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity	WBC=White Blood Cell; TEAE=Treatment-Emergent Adverse Event	From day 1 throughout the study period (day 421/week 60)
Secondary	Number of Subjects Experiencing a Relapse After Previously Achieving BVAS=0 During the Study	BVAS=Birmingham Vasculitis Activity Score; A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or; having achieved BVAS=0 at any time during the treatment period; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).	From day 1 throughout the study period (day 421/week 60)