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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02994927




Registration number
NCT02994927
Ethics application status
Date submitted
11/12/2016
Date registered
16/12/2016
Date last updated
22/07/2020

Titles & IDs
Public title
A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis
Scientific 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
Secondary ID [1] 0 0
ADVOCATE
Secondary ID [2] 0 0
CL010_168
Universal Trial Number (UTN)
Trial acronym
ADVOCATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ANCA-Associated Vasculitis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CCX168
Treatment: Drugs - Prednisone
Treatment: Drugs - Cyclophosphamide
Other interventions - Rituximab
Treatment: Drugs - Azathioprine

Experimental: CCX168 (avacopan) - CCX168 in combination with rituximab or in combination with cyclophosphamide followed by azathioprine

Active Comparator: Prednisone - Prednisone in combination with rituximab or in combination with cyclophosphamide followed by azathioprine


Treatment: Drugs: CCX168
Orally administered

Treatment: Drugs: Prednisone
Orally administered

Treatment: Drugs: Cyclophosphamide
Orally or intravenously administered

Other interventions: Rituximab
Intravenously administered

Treatment: Drugs: Azathioprine
Orally administered

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Remission - The proportion of patients achieving disease remission assessed by Birmingham Vasculitis Activity Score (BVAS) at Week 26
Timepoint [1] 0 0
26 weeks
Primary outcome [2] 0 0
Sustained remission - The proportion of patients achieving sustained disease remission assessed by BVAS at Week 52
Timepoint [2] 0 0
52 weeks
Secondary outcome [1] 0 0
Adverse events coded by MedDRA - Patient incidence of treatment-emergent serious adverse events, adverse events, and withdrawals due to adverse events
Timepoint [1] 0 0
60 weeks
Secondary outcome [2] 0 0
Glucocorticoid-induced toxicity - Glucocorticoid-induced toxicity as measured by the Glucocorticoid Toxicity Index
Timepoint [2] 0 0
26 weeks
Secondary outcome [3] 0 0
Response rapidity - Remission assessed by BVAS at week 4
Timepoint [3] 0 0
4 weeks
Secondary outcome [4] 0 0
Health-related quality of life - Change in health-related quality-of-life based on the Short Form-36 version 2 component and domain scores and the EuroQOL-5D-5L visual analogue scale (in mm) and index
Timepoint [4] 0 0
52 weeks
Secondary outcome [5] 0 0
Estimated glomerular filtration rate (eGFR) - Change from baseline in eGFR in mL/min/1.73^2
Timepoint [5] 0 0
52 weeks
Secondary outcome [6] 0 0
Urinary albumin:creatinine ratio (UACR) - Change from baseline in UACR in mg/g creatinine
Timepoint [6] 0 0
52 weeks
Secondary outcome [7] 0 0
Urinary monocyte chemoattractant protein-1 (MCP-1):creatinine ratio - Change from baseline in urinary MCP-1:creatinine ratio in pg/mg creatinine
Timepoint [7] 0 0
52 weeks
Secondary outcome [8] 0 0
Vasculitis Damage Index - Change from baseline in the Vasculitis Damage Index (VDI)
Timepoint [8] 0 0
52 weeks

Eligibility
Key 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 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-PR3 or anti-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 BVAS

- Estimated glomerular filtration rate =15 mL/minute/1.73 m^2 at screening
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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-TNF treatment, abatacept, alemtuzumab, 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Clinical Trial Site - Adelaide
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Clinical Trial Site - Auchenflower
Recruitment hospital [3] 0 0
Clinical Trial Site - Brisbane
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Clinical Trial Site - Clayton
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Clinical Trial Site - Woolloongabba
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- Adelaide
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- Southport
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- St Leonards
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- Westmead
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- Woolloongabba
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ChemoCentryx
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The aim of the trial is to assess the safety and efficacy of the orally-administered,
selective complement C5a receptor inhibitor CCX168 (avacopan) in inducing and sustaining
remission in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
(AAV).
Trial website
https://clinicaltrials.gov/show/NCT02994927
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Cass Kelleher, MD
Address 0 0
ChemoCentryx, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications