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ANCA-Associated VasculitisPhase 3ADVOCATENCT02994927

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

A Phase 3 study testing Avacopan, Prednisone and Cyclophosphamide in people with ANCA-Associated Vasculitis, run by Amgen at 198 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
ANCA-Associated Vasculitis
What is being tested?
Avacopan, Prednisone and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
331 participants
Where
198 sitesin 20 countries
Study dates
15 Mar 2017to 1 Nov 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

198 sites in 20 countries.

198 sites in 20 countries

United States41 sites

  • Clinical Trial Site

    Ann Arbor, Michigan, 48109

  • Clinical Trial Site

    Atlanta, Georgia, 30322

  • Clinical Trial Site

    Aurora, Colorado, 80045

  • Clinical Trial Site

    Baltimore, Maryland, 21224

  • Clinical Trial Site

    Boston, Massachusetts, 02114

  • Clinical Trial Site

    Boston, Massachusetts, 02118

  • Clinical Trial Site

    Chapel Hill, North Carolina, 27599

  • Clinical Trial Site

    Charleston, South Carolina, 29406

  • Clinical Trial Site

    Chicago, Illinois, 60637

  • Clinical Trial Site

    Cleveland, Ohio, 44195

  • Clinical Trial Site

    Columbus, Ohio, 43210

  • Clinical Trial Site

    Dallas, Texas, 75235

  • Clinical Trial Site

    Daytona Beach, Florida, 32117

  • Clinical Trial Site

    Duncansville, Pennsylvania, 16635

  • Clinical Trial Site

    Great Neck, New York, 11021

  • Clinical Trial Site

    Greenville, North Carolina, 27834

  • Clinical Trial Site

    Houston, Texas, 77030

  • Clinical Trial Site

    Huntsville, Alabama, 35801

  • Clinical Trial Site

    Indianapolis, Indiana, 46202

  • Clinical Trial Site

    Kansas City, Kansas, 66160

  • Clinical Trial Site

    Lexington, Kentucky, 40536

  • Clinical Trial Site

    Los Angeles, California, 90048

  • Clinical Trial Site

    Meridian, Idaho, 83605

  • Clinical Trial Site

    Mineola, New York, 11501

  • Clinical Trial Site

    Minneapolis, Minnesota, 55414

  • Clinical Trial Site

    New York, New York, 10021

  • Clinical Trial Site

    New York, New York, 10032

  • Clinical Trial Site

    Philadelphia, Pennsylvania, 19104

  • Clinical Trial Site

    Phoenix, Arizona, 85012

  • Clinical Trial Site

    Phoenix, Arizona, 85032

  • Clinical Trial Site

    Pittsburgh, Pennsylvania, 15225

  • Clinical Trial Site

    Providence, Rhode Island, 02903

  • Clinical Trial Site

    Rochester, Minnesota, 55905

  • Clinical Trial Site

    Salt Lake City, Utah, 84132

  • Clinical Trial Site

    Santa Monica, California, 90404

  • Clinical Trial Site

    Seattle, Washington, 98101

  • Clinical Trial Site

    Shreveport, Louisiana, 71101

  • Clinical Trial Site

    St Louis, Missouri, 63110

  • Clinical Trial Site

    Tampa, Florida, 33612

  • Clinical Trial Site

    Washington D.C., District of Columbia, 20007

  • Clinical Trial Site

    Winston-Salem, North Carolina, 27103

Other trials in United States

United Kingdom25 sites

  • Clinical Trial Site

    Aberdeen

  • Clinical Trial Site

    Basildon

  • Clinical Trial Site

    Birmingham

  • Clinical Trial Site

    Bristol

  • Clinical Trial Site

    Cambridge

  • Clinical Trial Site

    Canterbury

  • Clinical Trial Site

    Cardiff

  • Clinical Trial Site

    Carshalton

  • Clinical Trial Site

    Dorchester

  • Clinical Trial Site

    Dudley

  • Clinical Trial Site

    Exeter

  • Clinical Trial Site

    Glasgow

  • Clinical Trial Site

    Inverness

  • Clinical Trial Site

    Kirkcaldy

  • Clinical Trial Site

    Leeds

  • Clinical Trial Site

    Leicester

  • Clinical Trial Site

    Liverpool

  • Clinical Trial Site

    London

  • Clinical Trial Site

    Manchester

  • Clinical Trial Site

    Newcastle

  • Clinical Trial Site

    Nottingham

  • Clinical Trial Site

    Oxford

  • Clinical Trial Site

    Reading

  • Clinical Trial Site

    Salford

  • Clinical Trial Site

    Westcliff-on-Sea

Other trials in United Kingdom

Germany20 sites

  • Clinical Trial Site

    Aachen

  • Clinical Trial Site

    Bad Bramstedt

  • Clinical Trial Site

    Berlin

  • Clinical Trial Site

    Cologne

  • Clinical Trial Site

    Dresden

  • Clinical Trial Site

    Essen

  • Clinical Trial Site

    Freiburg im Breisgau

  • Clinical Trial Site

    Fulda

  • Clinical Trial Site

    Hamburg

  • Clinical Trial Site

    Hanover

  • Clinical Trial Site

    Heidelberg

  • Clinical Trial Site

    Jena

  • Clinical Trial Site

    Kirchheim unter Teck

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    Leipzig

  • Clinical Trial Site

    Lübeck

  • Clinical Trial Site

    Ludwigshafen

  • Clinical Trial Site

    Mannheim

  • Clinical Trial Site

    Munich

  • Clinical Trial Site

    Tübingen

  • Clinical Trial Site

    Villingen-Schwenningen

Other trials in Germany

Japan19 sites

  • Clinical Trial Site

    Aichi

  • Clinical Trial Site

    Akita

  • Clinical Trial Site

    Chiba

  • Clinical Trial Site

    Hiroshima

  • Clinical Trial Site

    Hokkaido

  • Clinical Trial Site

    Ishikawa

  • Clinical Trial Site

    Kagawa

  • Clinical Trial Site

    Kanagawa

  • Clinical Trial Site

    Kobe

  • Clinical Trial Site

    Miyazaki

  • Clinical Trial Site

    Nagoya

  • Clinical Trial Site

    Okayama

  • Clinical Trial Site

    Osaka

  • Clinical Trial Site

    Saitama

  • Clinical Trial Site

    Shimane

  • Clinical Trial Site

    Shizuoka

  • Clinical Trial Site

    Tokyo

  • Clinical Trial Site

    Toyama

  • Clinical Trial Site

    Yokohama

Other trials in Japan

Australia15 sites

  • Clinical Trial Site

    Adelaide

  • Clinical Trial Site

    Auchenflower

  • Clinical Trial Site

    Brisbane

  • Clinical Trial Site

    Clayton

  • Clinical Trial Site

    Concord

  • Clinical Trial Site

    Heidelberg

  • Clinical Trial Site

    Liverpool

  • Clinical Trial Site

    Nambour

  • Clinical Trial Site

    Nedlands

  • Clinical Trial Site

    Randwick

  • Clinical Trial Site

    Saint Albans

  • Clinical Trial Site

    Southport

  • Clinical Trial Site

    St Leonards

  • Clinical Trial Site

    Westmead

  • Clinical Trial Site

    Woolloongabba

Other trials in Australia

France15 sites

  • Clinical Trial Site

    Angers

  • Clinical Trial Site

    Bordeaux

  • Clinical Trial Site

    Boulogne-sur-Mer

  • Clinical Trial Site

    Brest

  • Clinical Trial Site

    Bron

  • Clinical Trial Site

    Caen

  • Clinical Trial Site

    Colmar

  • Clinical Trial Site

    Grenoble

  • Clinical Trial Site

    Marseille

  • Clinical Trial Site

    Metz

  • Clinical Trial Site

    Nantes

  • Clinical Trial Site

    Nîmes

  • Clinical Trial Site

    Paris

  • Clinical Trial Site

    Toulouse

  • Clinical Trial Site

    Valenciennes

Other trials in France

Italy9 sites

  • Clinical Trial Site

    Ancona

  • Clinical Trial Site

    Florence

  • Clinical Trial Site

    Genova

  • Clinical Trial Site

    Milan

  • Clinical Trial Site

    Monza

  • Clinical Trial Site

    Parma

  • Clinical Trial Site

    Reggio Emilia

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    Torino

  • Clinical Trial Site

    Udine

Other trials in Italy

Canada8 sites

  • Clinical Trial Site

    Calgary

  • Clinical Trial Site

    Greenfield Park

  • Clinical Trial Site

    Hamilton

  • Clinical Trial Site

    Montreal

  • Clinical Trial Site

    Québec

  • Clinical Trial Site

    Sherbrooke

  • Clinical Trial Site

    Toronto

  • Clinical Trial Site

    Vancouver

Other trials in Canada

Spain6 sites

  • Clinical Trial Site

    Badalona

  • Clinical Trial Site

    Barcelona

  • Clinical Trial Site

    Burela de Cabo

  • Clinical Trial Site

    Lleida

  • Clinical Trial Site

    Madrid

  • Clinical Trial Site

    San Sebastián

Other trials in Spain

Switzerland6 sites

  • Clinical Trial Site

    Basel

  • Clinical Trial Site

    Bern

  • Clinical Trial Site

    Fribourg

  • Clinical Trial Site

    Lausanne

  • Clinical Trial Site

    Sankt Gallen

  • Clinical Trial Site

    Zurich

Other trials in Switzerland

Denmark5 sites

  • Clinical Trial Site

    Aalborg

  • Clinical Trial Site

    Aarhus

  • Clinical Trial Site

    Copenhagen

  • Clinical Trial Site

    Odense

  • Clinical Trial Site

    Roskilde

Other trials in Denmark

New Zealand5 sites

  • Clinical Trial Site

    Christchurch

  • Clinical Trial Site

    Dunedin

  • Clinical Trial Site

    Grafton

  • Clinical Trial Site

    Hamilton

  • Clinical Trial Site

    Takapuna

Other trials in New Zealand

Sweden5 sites

  • Clinical Trial Site

    Linköping

  • Clinical Trial Site

    Lund

  • Clinical Trial Site

    Örebro

  • Clinical Trial Site

    Stockholm

  • Clinical Trial Site

    Uppsala

Other trials in Sweden

Belgium4 sites

  • Clinical Trial Site

    Antwerp

  • Clinical Trial Site

    Brussels

  • Clinical Trial Site

    Leuven

  • Clinical Trial Site

    Liège

Other trials in Belgium

Austria3 sites

  • Clinical Trial Site

    Feldkirch

  • Clinical Trial Site

    Graz

  • Clinical Trial Site

    Innsbruck

Other trials in Austria

Netherlands3 sites

  • Clinical Trial Site

    Groningen

  • Clinical Trial Site

    Leiden

  • Clinical Trial Site

    Rotterdam

Other trials in Netherlands

Norway3 sites

  • Clinical Trial Site

    Nordbyhagen

  • Clinical Trial Site

    Oslo

  • Clinical Trial Site

    Tromsø

Other trials in Norway

Czechia2 sites

  • Clinical Trial Site

    Olomouc

  • Clinical Trial Site

    Prague

Other trials in Czechia

Hungary2 sites

  • Clinical Trial Site

    Budapest

  • Clinical Trial Site

    Debrecen

Other trials in Hungary

Ireland2 sites

  • Clinical Trial Site

    Cork

  • Clinical Trial Site

    Dublin

Other trials in Ireland

About this study

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

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.

Read the detailed 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.

Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

Being tested
Avacopan, Prednisone, Cyclophosphamide, Rituximab, Azathioprine
Keywords
ANCA-associated vasculitis, complement, vasculitis, C5aR, avacopan, CCX168, MPA, GPA
Medical subject headings
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Vasculitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvacopanDrug

    Also called CCX168

    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.

  • PrednisoneDrug

    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.

  • CyclophosphamideDrug

    Orally or intravenously administered

  • RituximabBiological

    Intravenously administered

  • AzathioprineDrug

    Orally administered

Study groups in NCT02994927
Study groupRoleWhat they receive
Prednisone groupActive comparatorAvacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.
Receives: Drug: Prednisone; Drug: Cyclophosphamide; Biological: Rituximab; Drug: Azathioprine
Avacopan groupExperimentalAvacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Receives: Drug: Avacopan; Drug: Cyclophosphamide; Biological: Rituximab; Drug: Azathioprine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Week 26

  2. 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.

    Measured: Week 52

Secondary outcomes (26)

  1. Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs

    AEs=Adverse events

    SAEs=Serious adverse events

    TEAE=Treatment-emergent adverse event

    Measured: From day 1 throughout the study period (day 421/week 60)

  2. 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).

    Measured: Baseline, Week 13 and 26

  3. 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).

    Measured: Week 4

  4. 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).

    Measured: Baseline, Week 26 and 52

  5. 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:

    1. having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or
    2. 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).

    Measured: Week 52

  6. 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:

    1. having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or
    2. 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).

    Measured: Week 52

  7. 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

    Measured: Baseline, Week 26 and 52

  8. 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

    Measured: Baseline, Week 4, 26 and 52

  9. 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

    Measured: Baseline, Week 26 and 52

  10. 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).

    Measured: Baseline, Week 26 and 52

  11. Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5)

    Measured: Baseline, Week 26 and 52

  12. Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5)

    Measured: Baseline, Week 26 and 52

  13. Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5)

    Measured: Baseline, Week 26 and 52

  14. Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5)

    Measured: Baseline, Week 26 and 52

  15. Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5)

    Measured: Baseline, Week 26 and 52

  16. Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2)

    Measured: Baseline, Week 26 and 52

  17. Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2)

    Measured: Baseline, Week 26 and 52

  18. Change From Baseline in Vital Signs (1/5)

    Measured: Baseline, Week 26 and 52

  19. Change From Baseline in Vital Signs (2/5)

    Measured: Baseline, Week 26 and 52

  20. Change From Baseline in Vital Signs (3/5)

    Measured: Baseline, Week 26 and 52

  21. Change From Baseline in Vital Signs (4/5)

    Measured: Baseline, Week 26 and 52

  22. Change From Baseline in Vital Signs (5/5)

    BMI=Body Mass Index

    Measured: Baseline, Week 26 and 52

  23. Number of Subjects With Clinically Significant ECG Changes From Baseline

    Clinical significance was assessed by the individual reading of the ECGs

    ECG=Electrocardiogram

    Measured: From day 1 throughout the study period (day 421/week 60)

  24. 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

    Measured: From day 1 throughout the study period (day 421/week 60)

  25. Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity

    WBC=White Blood Cell

    TEAE=Treatment-Emergent Adverse Event

    Measured: From day 1 throughout the study period (day 421/week 60)

  26. 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:

    1. having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or
    2. 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).

    Measured: From day 1 throughout the study period (day 421/week 60)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2016 (estimated)
  2. Study start15 Mar 2017
  3. Primary completion7 Sep 2019
  4. Study completion1 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
331 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02994927
Sponsor's protocol ID
CL010_168
Other IDs
ADVOCATE
Acronym
ADVOCATE
Status last verified
Mar 2025
First submitted
11 Dec 2016
Last updated
24 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Publications

  • Geetha D, Neumann T, Karras A, Cid MC, Merkel PA, Bray S, Bozeman AM, Jayne DRW; Members of the ADVOCATE Study Group. Efficacy and safety of avacopan for treatment of patients with ANCA-associated vasculitis receiving cyclophosphamide. RMD Open. 2025 Oct 5;11(4):e005743. doi: 10.1136/rmdopen-2025-005743.

    PubMed 41052893

  • Geetha D, Dua A, Yue H, Springer J, Salvarani C, Jayne D, Merkel P; ADVOCATE Study Group. Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial. Ann Rheum Dis. 2024 Jan 11;83(2):223-232. doi: 10.1136/ard-2023-224816.

    PubMed 37979959

  • Soulsby WD. Journal Club Review of "Avacopan for the Treatment of ANCA-Associated Vasculitis". ACR Open Rheumatol. 2022 Jul;4(7):558-561. doi: 10.1002/acr2.11412. Epub 2022 Feb 15.

    PubMed 35167187

  • Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021 Feb 18;384(7):599-609. doi: 10.1056/NEJMoa2023386.

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  • Merkel PA, Jayne DR, Wang C, Hillson J, Bekker P. Evaluation of the Safety and Efficacy of Avacopan, a C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Treated Concomitantly With Rituximab or Cyclophosphamide/Azathioprine: Protocol for a Randomized, Double-Blind, Active-Controlled, Phase 3 Trial. JMIR Res Protoc. 2020 Apr 7;9(4):e16664. doi: 10.2196/16664.

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Avacopan, Prednisone and Cyclophosphamide in people with ANCA-Associated Vasculitis, run by Amgen at 198 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 198 sites in United States, United Kingdom, Germany, Japan, Australia and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Subjects Achieving Disease Remission at Week 26 (time frame: Week 26). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02994927, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.

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